Abstract:
The present invention provides a novel diazepine compound that blocks the I Kur  current or the Kv1.5 channel potently and more selectively than other K +  channels. The present invention relates to a diazepine compound represented by General Formula (1) 
     
       
                 
         
             
             
         
       
       
         or a salt thereof, 
         wherein R 1 , R 2 , R 3 , and R 4  are each independently hydrogen, lower alkyl, cyclo lower alkyl or lower alkoxy lower alkyl; 
         R 2  and R 3  may be linked to form lower alkylene; 
         A 1  is lower alkylene optionally substituted with one or more substituents selected from the group consisting of hydroxyl and oxo; 
         Y 1  and Y 2  are each independently —N═ or —CH═; 
         and 
         R 5  is group represented by 
       
     
     
       
                 
         
             
             
         
       
       
         wherein R 6  and R 7  are each independently hydrogen or organic group; 
         R 6  and R 7  may be linked to form a ring together with the neighboring group —X A —N—X B —; 
         X A  and X B  are each independently a bond, lower alkylene, etc.

Description:
TECHNICAL FIELD 
       [0001]    The present invention relates to a nitrogen-containing compound and a pharmaceutical composition containing the same. 
       BACKGROUND ART 
       [0002]    Atrial fibrillation (hereinafter referred to as “AF”) is the most frequently observed type of arrhythmia in clinical examinations. Although not a lethal arrhythmia, AF causes cardiogenic cerebral embolism, and is therefore recognized as an arrhythmia that greatly affects vital prognoses and QOL. It is known that the onset of AF increases with age, and that repeated AF strokes lead to chronic (serious) AF (The Journal of American Medical Association, 285, 2370-2375 (2001) and Circulation, 114, 119-123 (2006)). 
         [0003]    To prevent chronic AF, which causes difficulty in restoring sinus rhythm and increases the risk of cardiogenic cerebral embolism, early defibrillation and subsequent prevention of recurrence (maintenance of the sinus rhythm) are required. Antiarrhythmic drugs (classes I and III) are most commonly used as pharmacotherapy, but these drugs achieve insufficient therapeutic effects, while causing serious side effects such as a proarrhythmic effect (Am. J. Cardiol., 72, B44-B49 (1993)). 
         [0004]    The onset of AF is triggered by atrial premature contraction with underlining causes such as intra-atrial conduction delay, shortening and heterogeneity of the atrial refractory period (Nature Reviews DRUG DISCOVERY 4, 899-910 (2005)). It is known that the prolongation of refractory period of atrial muscle can terminate AF (defibrillation) or prevent the occurence of AF. The action potential duration of the mammalian cardiac muscle is predominantly determined by voltage-dependent K +  channels. Inhibition of the K +  channel prolongs myocardial action potential duration, which results in prolongation of the refractory period (Nature Reviews DRUG DISCOVERY 5, 1034-49 (2006)). The action mechanism of class III antiarrhythmic drugs (e.g., Dofetilide) is to inhibit rapid delayed rectifier K +  current (I Kr ), K +  current encoded by HERG. However, since I Kr  is present in both the atria and ventricles, such drugs might cause ventricular arrhythmias, such as torsades de pointes (Trends Pharmacol. soc., 22, 240-246 (2001)). 
         [0005]    Ultra-rapid delayed rectifier K +  current (I Kur ), K +  current encoded by Kv1.5, has been identified as K +  channel that is specifically expressed only in human atria (Cric. Res., 73, 1061-1076 (1993), J. Physiol., 491, 31-50 (1996) and Cric. Res., 80, 572-579 (1997)). Muscarine potassium current (I KACh ) encoded by two genes called GIRK1 and GIRK4 is known as a K +  channel specifically expressed in human atria (Nature 374, 135-141 (1995)). Accordingly, a pharmacologically acceptable substance that selectively blocks the I Kur  current (the Kv1.5 channel) or the I KACh  current (GIRK1/4 channel) can act selectively on the atrial muscle and is considered effective to exclude the proarrhythmic effect caused by prolonged action potential duration of the ventricular muscle. 
       SUMMARY OF INVENTION 
       [0006]    The present specification discloses three inventions (three nitrogen-containing compounds each having a different structure). The inventions are respectively expressed as a “First Invention”, “Second Invention”, and “Third Invention”, which are described in detail below. 
       1. First Invention (Diazepine Compound) 
       [0007]    The present inventors conducted extensive research to develop a compound that blocks the I Kur  current (Kv1.5 channel) and/or the I KACh  current (GIRK1/4 channel) potently and more selectively than other K +  channels. As a result, the inventors found that a novel diazepine compound represented by General Formula (1) below could be the desired compound. The present invention has been accomplished based on the above findings. 
         [0008]    The present invention provides diazepine compounds, and pharmaceutical compositions comprising the diazepine compounds as summarized in items 1 to 16 below. 
         [0009]    Item 1. A diazepine compound represented by General Formula (1) 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a salt thereof,
 
wherein R 1 , R 2 , R 3 , and R 4  are each independently hydrogen, lower alkyl, cyclo lower alkyl or lower alkoxy lower alkyl;
 
R 2  and R 3  may be linked to form lower alkylene;
 
A 1  is lower alkylene optionally substituted with one or more substituents selected from the group consisting of hydroxyl and oxo;
 
Y 1  and Y 2  are each independently —N═ or —CH═;
 
R 5  is group represented by
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 6  and R 7  are each independently hydrogen or an organic group;
 
R 6  and R 7  may be linked to form a ring together with the neighboring group —X A —N—X B —;
 
X A  and X B  are each independently a bond, alkylene, alkenylene, —CO—, —SO 2 —, or —CONH—, wherein each of the alkylene and alkenylene chains can optionally contain one or more substituents selected from the group consisting of —S—, —C(═S)—SO 2 —, —CO—, —O—, —NH—, —CONH— and —SO 2 NH—, and the hydrogen atom (H) bonded to the nitrogen atom (N) in X A  and X B  is optionally substituted with a substituent selected from the group consisting of lower alkyl, phenyl lower alkyl and phenyl.
 
         [0010]    Item 2. A diazepine compound or a salt thereof according to Item 1, wherein R 6  and R 7  are each independently hydrogen, lower alkyl, cyclo lower alkyl, aryl or heterocyclic group, each of which is optionally substituted, and X A  and X B  are each independently a bond, lower alkylene, lower alkenylene, —CO—, —SO 2 —, -lower alkylene-SO 2 —, -lower alkylene-CO—, -lower alkenylene-CO—, -lower alkylene-CO—N(lower alkyl)-lower alkylene-, —N(lower alkyl)-lower alkylene-, —CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-, —N(phenyl lower alkyl)-lower alkylene-, —CO-lower alkylene-CO—, —CO—NH-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-O—, -lower alkylene-NH-lower alkylene-, -lower alkylene-SO 2 —NH-lower alkylene-, —N(lower alkyl)-CO-lower alkylene-, —N(lower alkyl)-lower alkylene-CO—, —N(lower alkyl)-lower alkylene-N(lower alkyl)-lower alkylene-, —N(phenyl)-lower alkylene-CO—, —N(phenyl)-lower alkylene-CO—, —NH—CO—, —NH—CO-lower alkylene-, —NH-lower alkylene-, —O-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-CO—, —NH-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —S-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —SO 2 —N(lower alkyl)-lower alkylene-, —SO 2 —NH-lower alkylene-, -lower alkenylene-CO—N(lower alkyl)-lower alkylene-, lower alkylene-N(phenyl lower alkyl)-lower alkylene-, —N(phenyl lower alkyl)-lower alkylene-, —N(phenyl)-lower alkylene-CO—N(lower alkyl)-lower alkylene-, or —CO-lower alkylene-O—CO-lower alkylene-O—. 
         [0011]    Item 3. A diazepine compound or a salt thereof according to Item 2, wherein R 6  and R 7  are each independently hydrogen, lower alkyl, cyclo lower alkyl, aryl or saturated or unsaturated monocyclic or polycyclic heterocyclic groups containing at least one hetero atom selected from the group consisting of oxygen, sulfur and nitrogen, each of which is optionally substituted. 
         [0012]    Item 4. A diazepine compound or a salt thereof according to Item 3, wherein R 6  and R 7  are each independently hydrogen, lower alkyl, cyclo lower alkyl, phenyl, naphthyl, piperidyl, piperazinyl, pyrrolidinyl, morpholinyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrrolyl, triazolyl, imidazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazo[2,1-b]thiazolyl, thieno[2,3-b]pyrazinyl, 2,3-dihydroimidazo[2,1-b]thiazolyl, benzothiazolyl, indolyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, benzothienyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzo[b]furyl, benzofuryl, indazolyl, furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, thieno[3,2-c]pyridyl, 4,5-dihydrothieno[3,2-c]pyridyl, thieno[2,3-b]pyridyl, 6,7-dihydrothieno[2,3-b]pyridyl, benzo[1,3]dioxolyl, benzisoxazolyl, pyrazolo[2,3-a]pyridyl, indolizinyl, 2,3-dihydroindolyl, isoquinolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydro-1H-isoquinolyl, carbostyril, 3,4-dihydrocarbostyril, quinolyl, 1,4-dihydroquinolyl, 1,2-dihydroquinolyl, 3,4-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, pyrido[3,4-d]imidazolyl, pyrido[2,3-d]imidazolyl, chromanyl, 5,6,7,8-tetrahydroisoquinolyl, 3,4-dihydro-1H-isoquinolyl, 3,4-dihydroisoquinolyl, naphthyridinyl, 1,4-benzodioxanyl, cinnolinyl, quinoxalinyl, 2,3-dihydrobenz-1,4-oxazinyl, azetidinyl, 1,2,4-oxadiazolyl and azepanyl, each of which is optionally substituted. 
         [0013]    Item 5. A diazepine compound or a salt thereof according to Item 4, wherein R 6  and R 7  are each independently selected from the group consisting of the following substituents (1) to (54): 
         [0000]    (1) hydrogen;
 
(2) lower alkyl;
 
(3) cyclo lower alkyl optionally substituted with one or more phenyl lower alkoxys;
 
(4) phenyl optionally substituted with one or more substituents selected from the group consisting of the following (4-1) to (4-27):
       (4-1) cyano;   (4-2) hydroxyl;   (4-3) halogen;   (4-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, lower alkoxy, imidazolyl, 2-oxo-1,2,3,4-tetrahydroquinolyl and morpholinyl;   (4-5) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of amino and lower alkyl amino;   (4-6) pyridyl;   (4-7) thienyl;   (4-8) piperazinyl optionally substituted with one or more lower alkyls;   (4-9) phenyl;   (4-10) pyrazolyl optionally substituted with one or more lower alkyls;   (4-11) pyrimidinyl optionally substituted with one or more lower alkyls;   (4-12) piperidyl optionally substituted with one or more lower alkyls;   (4-13) furyl;   (4-14) carboxy;   (4-15) lower alkoxycarbonyl;   (4-16) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and lower alkylsulfonyl;   (4-17) lower alkylthio;   (4-18) triazolyl;   (4-19) imidazolyl;   (4-20) pyrrolidinyl optionally substituted with one or more oxos;   (4-21) lower alkylsulfonyl;   (4-22) lower alkylenedioxy optionally substituted with one or more halogens;   (4-23) nitro;   (4-24) oxazolyl;   (4-25) thiazolyl optionally substituted with one or more lower alkyls;   (4-26) lower alkanoyl; and   (4-27) morpholinyl;
 
(5) naphthyl;
 
(6) furyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen, carboxy, sulfo, pyridyloxy, lower alkoxycarbonyl and phenyl;
 
(7) thienyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkylenedioxy, carboxy, halogen, pyridyl, lower alkoxy, lower alkoxycarbonyl, oxazolyl and furyl;
 
(8) imidazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl and halogen;
 
(9) pyrazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen or lower alkoxy; cyclo lower alkyl; halogen; phenyl optionally substituted with lower alkoxy; furyl and thienyl;
 
(10) oxazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(11) isoxazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl, thienyl and furyl;
 
(12) thiazolyl optionally substituted With one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen or lower alkoxy; phenyl; phenoxy and lower alkanoylamino;
 
(13) pyrrolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and lower alkoxycarbonyl;
 
(14) triazolyl optionally substituted with one or more lower alkyls;
 
(15) pyridyl optionally substituted with one or more substituents selected from the group consisting of the following (15-1) to (15-14):
   (15-1) halogen;   (15-2) cyano;   (15-3) amino optionally substituted with one or more substituents selected from the group consisting of lower alkanoyl and lower alkylsulfonyl;   (15-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, lower alkoxy, lower alkanoyloxy, cyclo lower alkyl amino, lower alkyl amino, lower alkanoyl amino, hydroxyl and pyrrolidinyl optionally substituted with one or more hydroxyls;   (15-5) oxo;   (15-6) hydroxyl;   (15-7) lower alkoxy optionally substituted with one or more phenyls;   (15-8) pyrrolidinyl;   (15-9) lower alkanoyl;   (15-10) morpholinyl;   (15-11) phenoxy;   (15-12) pyrazolyl;   (15-13) thienyl; and   (15-14) N-oxide
 
(16) pyrimidinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(17) pyridazinyl;
 
(18) pyrazinyl optionally substituted with one or more phenyl lower alkoxys;
 
(19) imidazo[2,1-b]thiazolyl optionally substituted with one or more halogens;
 
(20) thieno[2,3-b]pyrazinyl;
 
(21) 2,3-dihydroimidazo[2,1-b]thiazolyl optionally substituted with one or more phenyls;
 
(22) benzothiazolyl optionally substituted with one or more lower alkyls;
 
(23) indolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and halogen;
 
(24) imidazo[1,2-a]pyridyl or imidazo[1,5-a]pyridyl, each of which is optionally substituted with one or more lower alkyls;
 
(25) benzothienyl optionally substituted with one or more lower alkyls;
 
(26) benzimidazolyl optionally substituted with one or more lower alkyls;
 
(27) 2,3-dihydrobenzo[b]furyl;
 
(28) benzofuryl optionally substituted with one or more halogens;
 
(29) indazolyl optionally substituted with one or more lower alkyls;
 
(30) furo[2,3-c]pyridyl or 6,7-dihydrofuro[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl optionally substituted with lower alkoxy;
 
(31) furo[3,2-c]pyridyl or 4,5-dihydrofuro[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl optionally substituted with halogen or lower alkoxy, halogen, furyl, pyridyl and phenyl optionally substituted with one or more substituents selected from the group consisting of amino and lower alkoxy;
 
(32) thieno[2,3-c]pyridyl or 6,7-dihydrothieno[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo group and lower alkyl;
 
(33) thieno[3,2-c]pyridyl or 4,5-dihydrothieno[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(34) thieno[2,3-b]pyridyl;
 
(35) benzo[1,3]dioxolyl optionally substituted with one or more halogens;
 
(36) benzisoxazolyl;
 
(37) pyrazolo[2,3-a]pyridyl;
 
(38) indolizinyl;
 
(39) 2,3-dihydroindolyl optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl and lower alkanoyl;
 
(40) isoquinolyl or 1,2-dihydroisoquinolyl, each of which is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, halogen and oxo;
 
(41) 1,2,3,4-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(42) quinolyl optionally substituted with one or more substituents selected from the group consisting of amino optionally substituted with one or two lower alkyls, lower alkoxy, lower alkyl and oxo
 
(43) 1,2,3,4-tetrahydroquinolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, pyridyl lower alkyl, aralkyl, lower alkoxy and oxo;
 
(44) 1,2-dihydroquinolyl optionally substituted with one or more substituents selected from the group consisting of amino optionally substituted with one or two lower alkyls, lower alkoxy, lower alkyl and oxo;
 
(45) chromanyl optionally substituted with one or more lower alkyls;
 
(46) 5,6,7,8-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(47) 3,4-dihydroisoquinolyl optionally substituted with one or more oxos;
 
(48) naphthyridinyl;
 
(49) 1,4-benzodioxanyl;
 
(50) cinnolinyl;
 
(51) quinoxalinyl;
 
(52) 2,3-dihydrobenz-1,4-oxazinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo;
 
(53) 2,3-dihydro-1H-benzo[d]imidazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo; and
 
(54) piperidyl optionally substituted with one or more aryl carbonyls.
       
 
         [0055]    Item 6. A diazepine compound or a salt thereof according to Item 5, wherein R 6  and R 7  are each independently (1), (4a), (6a), (7a), (8a), (9a), (10a), (11a), (12a), (15a), (16a), (17), (18), (23a), (24a), (24b), (26), (29), (30a), (30b), (31a), (31b), (32a), (32b), (33a), (33b), (35), (40a), (40b), (42a), (43a), (44a), and (53): (1) hydrogen; 
         [0000]    (4a) phenyl optionally substituted with one or more substituents selected from the group consisting of the following (4-1), (4-2), (4-4), (4a-5), (4-10), (4a-16), (4-18), (4-19), (4-23), (4-26), and (4-27):
       (4-1) cyano;   (4-2) hydroxyl;   (4-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, 2-oxo-1,2,3,4-tetrahydroquinolyl, lower alkoxy, imidazolyl, and morpholinyl;   (4a-5) lower alkoxy;   (4-10) pyrazolyl optionally substituted with one or more lower alkyls;   (4a-16) amino optionally substituted with one or more lower alkylsulfonyls;   (4-18) triazolyl;   (4-19) imidazolyl;   (4-23) nitro;   (4-26) lower alkanoyl; and   (4-27) morpholinyl;
 
(6a) furyl optionally substituted with one or more lower alkyls optionally substituted with halogen;
 
(7a) thienyl optionally substituted with one or more lower alkyls;
 
(8a) imidazolyl optionally substituted with one or more lower alkyls;
 
(9a) pyrazolyl optionally substituted with one or more lower alkyls optionally substituted with lower alkoxy;
 
(10a) oxazolyl optionally substituted with one or more lower alkyls;
 
(11a) isoxazolyl optionally substituted with one or more lower alkyls;
   (12a) triazolyl optionally substituted with one or more lower alkyls optionally substituted with halogen;
 
(15a) pyridyl optionally substituted with one or more substituents selected from the group consisting of the following (15-1) to (15-5), (15a-7), (15-9), (15-11), (15-12) and (15-14):
   (15-1) halogen;   (15-2) cyano;   (15-3) amino optionally substituted with one or more substituents selected from the group consisting of lower alkanoyl and lower alkylsulfonyl;   (15-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, lower alkoxy, lower alkanoyloxy, cyclo lower alkyl amino, lower alkyl amino, lower alkanoyl amino, hydroxyl and pyrrolidinyl optionally substituted with one or more hydroxyls;   (15-5) oxo;   (15a-7) lower alkoxy;   (15-9) lower alkanoyl;   (15-11) phenoxy;   (15-12) pyrazolyl; and   (15-14) N-oxide
 
(16a) pyrimidinyl optionally substituted with one or more lower alkyls;
 
(17) pyridazinyl
 
(18) pyrazinyl optionally substituted with one or more phenyl lower alkoxys;
 
(23a) indolyl optionally substituted with one or more lower alkyls;
 
(24a) imidazo[1,2-a]pyridyl;
 
(24b) imidazo[1,5-a]pyridyl optionally substituted with one or more lower alkyls;
 
(26) benzimidazolyl optionally substituted with one or more lower alkyls;
 
(29) indazolyl optionally substituted with one or more lower alkyls;
 
(30a) furo[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(30b) 6,7-dihydrofuro[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(31a) furo[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(31b) 4,5-dihydrofuro[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl optionally substituted with halogen or lower alkoxy;
 
(32a) thieno[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(32b) 6,7-dihydrothieno[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo group and lower alkyl;
 
(33a) thieno[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(33b) 4,5-dihydrothieno[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(35a) benzo[1,3]dioxolyl;
 
(40a) isoquinolyl optionally substituted with one or more oxos;
 
(40b) 1,2-dihydroisoquinolyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(42a) quinolyl optionally substituted with one or more oxos;
 
(43a) 1,2,3,4-tetrahydroquinolyl optionally substituted with one or more substituents selected from the group consisting of aralkyl (e.g., phenyl lower alkyl, etc.), pyridyl lower alkyl and oxo;
 
(44) 1,2-dihydroquinolyl optionally substituted with one or more oxos; and
 
(53) 2,3-dihydrobenzo[d]imidazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo.
       
 
         [0078]    Item 7. A diazepine compound or a salt thereof according to Item 6, wherein R 6  and R 7  are each independently phenyl, pyridyl, pyrazolyl, indolyl, 4,5-dihydrofuro[3,2-c]pyridyl, and 1,2-dihydroisoquinolyl, each of which is optionally substituted with one or two substituents selected from the group consisting of oxo, lower alkyl, lower alkoxy lower alkyl, and lower alkylsulfonylamino. 
         [0079]    Item 8. A diazepine compound or a salt thereof according to Item 7, which is selected from the group consisting of the following compounds:
   1-ethyl-3,3,5-trimethyl-7-(3-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-ethyl-3,3,5-trimethyl-7-(2-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}ethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-ethyl-3,3,5-trimethyl-7-(2-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}ethyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione,   1-ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-4-methyl-N-(2-pyridin-3-ylethyl)benzamide,   N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide,   7-{[N-benzyl-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   N-(2-{[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)(2-pyridin-3-ylethyl)amino]methyl}-phenyl)methanesulfonamide,   7-{[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-(2-pyridin-3-ylethyl)acetamide.   
 
         [0093]    Item 9. A diazepine compound according to Item 8, which is selected from the group consisting of the following compounds: 1-ethyl-3,3,5-trimethyl-7-(3-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}propyl)-1,5-dihyd robenzo[b][1,4]diazepine-2,4-dione dihydrochloride,
   1-ethyl-3,3,5-trimethyl-7-(2-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}ethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride,   1-ethyl-3,3,5-trimethyl-7-(2-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}ethyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione dihydrochloride,   1-ethyl-3,3,5-trimethyl-7-[2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]ethyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride,   1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-[(1-oxo-1H-isoquinolin-2-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride,   N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-4-methyl-N-(2-pyridin-3-ylethyl)benzamide hydrochloride,   N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide,   7-{[N-benzyl-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride,   N-(2-{[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)(2-pyridin-3-ylethyl)amino]methyl}phenyl)methanesulfonamide dihydrochloride,   7-{[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione,   1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione, and   N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-(2-pyrid in-3-ylethyl)acetamide hydrochloride.   
 
         [0106]    Item 10. A diazepine compound or a salt thereof according to Item 1, wherein Y 1  and Y 2  are each —CH═. 
         [0107]    Item 11. A pharmaceutical composition comprising a diazepine compound or a salt thereof according to Item 1, and a pharmacologically acceptable carrier. 
         [0108]    Item 12. A pharmaceutical composition according to Item 11 for preventing and/or treating arrhythmia. 
         [0109]    Item 13. A diazepine compound or a salt thereof according to Item 1 for use in the pharmaceutical composition. 
         [0110]    Item 14. Use of a diazepine compound or a salt thereof according to Item 1 as a pharmaceutical composition. 
         [0111]    Item 15. Use of a diazepine compound or a salt thereof according to Item 1 for the production of a pharmaceutical composition. 
         [0112]    Item 16. A method of preventing and/or treating arrhythmia, comprising administering to a patient a diazepine compound or a salt thereof according to Item 1. 
         [0113]    The groups represented by, or substituents of, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , A 1 , X A , X B , Y 1  and Y 2  in the specification are described below. 
         [0114]    The term “one or more” may be preferably 1 to 6, more preferably 1 to 3. 
         [0115]    Examples of “lower alkyl” include linear or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, n-hexyl, isohexyl, and 3-methylpentyl. 
         [0116]    Examples of “alkylene” include linear or branched alkylene groups having 1 to 12 carbon atoms, such as the following “lower alkylene”, heptamethylene, octamethylene, decamethylene, and dodecamethylene. 
         [0117]    Examples of “lower alkylene” include linear or branched alkylene groups having 1 to 6 carbon atoms, such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, dimethylmethylene, tetramethylene, pentamethylene, and hexamethylene. 
         [0118]    Examples of “alkenylene” include linear or branched alkylene groups having 2 to 12 carbon atoms, such as the following “lower alkenylene”, heptenylene, octenylene, decenylene, and dodecenylene. 
         [0119]    Examples of “lower alkenylene” include linear or branched alkylene groups having 2 to 6 carbon atoms, such as, ethenylene, propenylene, butenylene, pentenylene, and hexenylene. 
         [0120]    Examples of “cyclo lower alkyl” include linear or branched cyclo alkyl having 3 to 8 carbon atoms, preferably 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl and cyclohexylmethyl. 
         [0121]    Examples of “lower alkoxy” include linear or branched alkoxy groups having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy, and 3-methylpentyloxy. 
         [0122]    Examples of “halogen” are fluorine, chlorine, bromine, and iodine. 
         [0123]    Examples of “lower alkylenedioxy” include linear or branched alkylene groups having 1 to 4 carbon atoms, such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy. 
         [0124]    Examples of “lower alkanoyl” include linear or branched alkanoyl groups having 1 to 6 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl. 
         [0125]    Examples of “lower alkoxycarbonyl” include (linear or branched alkoxy having 1 to 6 carbon atoms)carbonyls, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and tert-butoxycarbonyl. 
         [0126]    Examples of “aralkyl group” include lower alkyl group substituted with one or more aryl groups, such as benzyl and phenethyl. 
         [0127]    Examples of “organic group” include lower alkyl, cyclo lower alkyl, aryl, and heterocyclic group, each of which is optionally substituted. 
         [0128]    Examples of “aryl group” include monocyclic or polycyclic aryl groups, such as phenyl, tolyl, xylyl, and naphthyl. 
         [0129]    Examples of “aroyl group” include benzoyl and naphthoyl. 
         [0130]    Examples of “heterocyclic group” include saturated or unsaturated monocyclic or polycyclic heterocyclic groups containing at least one hetero atom selected from the group consisting of oxygen, sulfur and nitrogen. Examples of preferable heterocyclic groups include the following (a) to (n): 
         [0131]    (a) unsaturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, and its N-oxide, tetrahydropyridyl (e.g., 1,2,3,6-tetrahydropyridyl), pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), dihydrotriazinyl (e.g., 4,5-dihydro-1,2,4-triazinyl, 2,5-dihydro-1,2,4-triazinyl, etc.), etc.; 
         [0132]    (b) saturated 3 to 8-membered, preferably 5 or 7-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, pyrazolidinyl, piperazinyl, azepanyl, 1,4-diazepanyl, etc.; 
         [0133]    (c) saturated or unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 5 nitrogen atom(s), for example, decahydroquinolyl, indolyl, dihydroindolyl (e.g., 2,3-dihydroindolyl, etc.), isoindolyl, indolizinyl, benzimidazolyl, dihydrobenzimidazolyl (e.g., 2,3-dihydro-1H-benzo[d]imidazolyl, etc.), quinolyl, dihydroquinolyl (e.g. 1,4-dihydroquinolyl, 1,2-dihydroquinolyl, etc.), tetrahydroquinolyl (1,2,3,4-tetrahydroquinolyl, etc.), isoquinolyl, dihydroisoquinolyl (e.g., 3,4-dihydro-1H-isoquinolyl, 1,2-dihydroisoquinolyl, etc.), tetrahydroisoquinolyl (e.g., 1,2,3,4-tetrahydro-1H-isoquinolyl, 5,6,7,8-tetrahydroisoquinolyl, etc.), carbostyril, dihydrocarbostyril (e.g., 3,4-dihydrocarbostyril, etc.), indazolyl, benzotriazolyl (e.g. benzo[d][1,2,3]triazolyl, etc.), tetrazolopyridyl, tetrazolopyridazinyl (e.g., tetrazolo[1,5-b]pyridazinyl, etc.), dihydrotriazolopyridazinyl, imidazopyridyl (e.g., imidazo[1,2-a]pyridyl, imidazo[4,5-c]pyridyl, imidazo[1,5-a]pyridyl, etc.), naphthyridinyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolopyridyl (e.g., pyrazolo[2,3-a]pyridyl, etc.), tetrahydropyridoindolyl (e.g., 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, etc.), azasbicyclooctanyl (e.g., (1R,5S)-8-azabicyclo[3.2.1]octanyl), etc.; 
         [0134]    (d) saturated or unsaturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s), for example, furyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl, etc.), tetrahydrofuryl, etc.; 
         [0135]    (e) unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 3 oxygen atom(s), for example, benzofuryl, dihydrobenzofuryl (e.g. 2,3-dihydrobenzo[b]furyl, etc.), chromanyl, benzodioxanyl (e.g., 1,4-benzodioxanyl, etc.), benzodioxolyl (benzo[1,3]dioxolyl, etc.), etc.; 
         [0136]    (f) unsaturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.), etc.; 
         [0137]    (g) saturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, etc.; 
         [0138]    (h) unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, benzisoxazolyl, dihydrobenzoxazinyl (e.g., 2,3-dihydrobenz-1,4-oxazinyl, etc.), furopyridyl (e.g., furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, etc.), furopyrrolyl (e.g., furo[3,2-b]pyrrolyl etc.), etc.; 
         [0139]    (i) unsaturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl, thiazolinyl, thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,2,3-thiadiazolyl, etc.), isothiazolyl, etc.; 
         [0140]    (j) saturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, etc.; 
         [0141]    (k) unsaturated 3 to 8-membered, preferably 5 or 6-membered heteromonocyclic groups containing a sulfur atom, for example, thienyl, etc.; 
         [0142]    (l) unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 3 sulfur atom(s), for example, benzothienyl (e.g. benzo[b]thienyl, etc.); 
         [0143]    (m) unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolyl, thienopyridyl (e.g., thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, thieno[3,2-c]pyridyl, 4,5-dihydrothieno[3,2-c]pyridyl, thieno[2,3-b]pyridyl, 6,7-dihydrothieno[2,3-b]pyridyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridyl, etc.), imidazothiazolyl (e.g., imidazo[2,1-b]thiazolyl, etc.), dihydroimidazothiazolyl (e.g., 2,3-dihydroimidazo[2,1-b]thiazolyl, etc.), thienopyrazinyl (e.g., thieno[2,3-b]pyrazinyl, etc.), etc.; and 
         [0144]    (n) saturated or unsaturated 7- to 12-membered heterocyclic spiro groups containing 1 to 2 nitrogen atom(s), for example, azaspiroundecanyl (e.g., 3-azaspiro[5.5]undecanyl), etc.; and the like; 
         [0145]    wherein said heterocyclic groups may be substituted with one or more suitable substituents. 
         [0146]    Examples of more preferable heterocyclic groups include piperidyl, piperazinyl, pyrrolidinyl, morpholinyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, triazolyl, isothiazolyl, pyrrolyl, triazolyl, imidazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazo[2,1-b]thiazolyl, thieno[2,3-b]pyrazinyl, 2,3-dihydroimidazo[2,1-b]thiazolyl, benzothiazolyl, indolyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, benzothienyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydrobenzo[b]furyl, benzofuryl, indazolyl, furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, thieno[3,2-c]pyridyl, 4,5-dihydrothieno[3,2-c]pyridyl, thieno[2,3-b]pyridyl, 6,7-dihydrothieno[2,3-b]pyridyl, benzo[1,3]dioxolyl, benzisoxazolyl, pyrazolo[2,3-a]pyridyl, indolizinyl, 2,3-dihydroindolyl, isoquinolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydro-1H-isoquinolyl, carbostyril, 3,4-dihydrocarbostyril, quinolyl, 1,4-dihydroquinolyl, 1,2-dihydroquinolyl, 3,4-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, pyrido[3,4-d]imidazolyl, pyrido[2,3-d]imidazolyl, chromanyl, 5,6,7,8-tetrahydroisoquinolyl, 3,4-dihydro-1H-isoquinolyl, 3,4-dihydroisoquinolyl, naphthyridinyl, 1,4-benzodioxanyl, cinnolinyl, quinoxalinyl, 2,3-dihydrobenz-1,4-oxazinyl, azetidinyl, 1,2,4-oxadiazolyl, and azepanyl, each of which is optionally substituted. 
         [0147]    Substituents of “aryl group which is optionally substituted” represented by R 6  and R 7  are independently one or more substituents selected from the group consisting of: 
         [0000]    (a1) cyano;
 
(a2) hydroxyl;
 
(a3) halogen;
 
(a4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, lower alkoxy, imidazolyl, 2-oxo-1,2,3,4-tetrahydroquinolyl and morpholinyl;
 
(a5) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of amino and lower alkyl amino;
 
(a6) pyridyl;
 
(a7) thienyl;
 
(a8) piperazinyl optionally substituted with one or more lower alkyls;
 
(a9) phenyl;
 
(a10) pyrazolyl optionally substituted with one or more lower alkyls;
 
(a11) pyrimidinyl optionally substituted with one or more lower alkyls;
 
(a12) piperidyl optionally substituted with one or more lower alkyls;
 
(a13) furyl;
 
(a14) carboxy;
 
(a15) lower alkoxycarbonyl;
 
(a16) amino optionally substituted with one or more substituents selected from the group consisting of lower alkanoyl and lower alkylsulfonyl;
 
(a17) lower alkylthio;
 
(a18) triazolyl;
 
(a19) imidazolyl;
 
(a20) pyrrolidinyl optionally substituted with one or more oxos;
 
(a21) lower alkylsulfonyl;
 
(a22) lower alkylenedioxy optionally substituted with one or more halogens;
 
(a23) nitro;
 
(a24) oxazolyl;
 
(a25) thiazolyl optionally substituted with one or more lower alkyls;
 
(a26) lower alkanoyl;
 
(a27) sulfo; and
 
(a28) morpholinyl.
 
         [0148]    Substituents of “heterocyclic group which is optionally substituted” represented by R 6  and R 7  are independently one or more substituents selected from the group consisting of: 
         [0000]    (h1) oxo;
 
(h2) lower alkyl optionally substituted with one or more substitutents selected from the group consisting of the following (h2-1) to (h2-10):
       (h2-1) halogen;   (h2-2) hydroxyl;   (h2-3) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, cyclo lower alkyl and lower alkanoyl;   (h2-4) pyridyl;   (h2-5) lower alkanoyloxy;   (h2-6) lower alkoxy;   (h2-7) aryloxy;   (h2-8) pyrimidinyl;   (h2-9) pyrrolidinyl optionally substituted with one or more hydroxyls; and   (h2-10) imidazolyl optionally substituted with one or more lower alkyls;
 
(h3) cyclo lower alkyl;
 
(h4) lower alkoxy optionally substituted with one or more substitutents selected from the group consisting of pyridyl and aryl;
 
(h5) aryl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with one or more halogens; lower alkoxy; lower alkanoyl; hydroxyl; halogen; carboxy; lower alkoxycarbonyl; amino; lower alkyl amino, aryl and cyano;
 
(h6) aralkyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkanoyl, hydroxyl, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkyl amino, cyano and oxo;
 
(h7) heterocyclic group optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkanoyl, hydroxyl, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkyl amino, cyano and oxo;
 
(h8) hydroxyl;
 
(h9) halogen;
 
(h10) carboxy;
 
(h11) lower alkanoyl;
 
(h12) lower alkoxycarbonyl;
 
(h13) lower alkylenedioxy;
 
(h14) cyano;
 
(h15) nitro;
 
(h16) sulfo;
 
(h17) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, aryl, aroyl, lower alkylsulfonyl and lower alkanoyl;
 
(h18) lower alkylthio;
 
(h19) lower alkylsulfonyl; and
 
(h20) aryloxy.
       
 
         [0159]    Preferable substituents represented by R 6  and R 7  are each independently selected from the group consisting of the following substituents (1) to (54): 
         [0000]    (1) hydrogen;
 
(2) lower alkyl;
 
(3) cyclo lower alkyl optionally substituted with one or more phenyl lower alkoxys;
 
(4) phenyl optionally substituted with one or more substituents selected from the group consisting of the following (4-1) to (4-27):
 
(4-1) cyano;
 
(4-2) hydroxyl;
       (4-3) halogen;   (4-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, lower alkoxy, imidazolyl, 2-oxo-1,2,3,4-tetrahydroquinolyl and morpholinyl;   (4-5) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of amino and lower alkyl amino;   (4-6) pyridyl;   (4-7) thienyl;   (4-8) piperazinyl optionally substituted with one or more lower alkyls;   (4-9) phenyl;   (4-10) pyrazolyl optionally substituted with one or more lower alkyls;   (4-11) pyrimidinyl optionally substituted with one or more lower alkyls;   (4-12) piperidyl optionally substituted with one or more lower alkyls;   (4-13) furyl;   (4-14) carboxy;   (4-15) lower alkoxycarbonyl;   (4-16) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and lower alkylsulfonyl;   (4-17) lower alkylthio;   (4-18) triazolyl;   (4-19) imidazolyl;   (4-20) pyrrolidinyl optionally substituted with one or more oxos;   (4-21) lower alkylsulfonyl;   (4-22) lower alkylenedioxy optionally substituted with one or more halogens;   (4-23) nitro;   (4-24) oxazolyl;   (4-25) thiazolyl optionally substituted with one or more lower alkyls;   (4-26) lower alkanoyl; and   (4-27) morpholinyl;
 
(5) naphthyl;
 
(6) furyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen, carboxy, sulfo, pyridyloxy, lower alkoxycarbonyl and phenyl;
 
(7) thienyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkylenedioxy, carboxy, halogen, pyridyl, lower alkoxy, lower alkoxycarbonyl, oxazolyl and furyl;
 
(8) imidazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl and halogen;
 
(9) pyrazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen or lower alkoxy; cyclo lower alkyl; halogen; phenyl optionally substituted with lower alkoxy; furyl and thienyl;
 
(10) oxazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(11) isoxazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl, thienyl and furyl;
 
(12) thiazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen or lower alkoxy; phenyl; phenoxy and lower alkanoylamino;
 
(13) pyrrolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and lower alkoxycarbonyl;
 
(14) triazolyl optionally substituted with one or more lower alkyls;
 
(15) pyridyl optionally substituted with one or more substituents selected from the group consisting of the following (15-1) to (15-14):
   (15-1) halogen;   (15-2) cyano;   (15-3) amino optionally substituted with one or more substituents selected from the group consisting of lower alkanoyl and lower alkylsulfonyl;   (15-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, lower alkoxy, lower alkanoyloxy, cyclo lower alkyl amino, lower alkyl amino, lower alkanoyl amino, hydroxyl and pyrrolidinyl optionally substituted with one or more hydroxyls;   (15-5) oxo;   (15-6) hydroxyl;   (15-7) lower alkoxy optionally substituted with one or more phenyls;   (15-8) pyrrolidinyl;   (15-9) lower alkanoyl;   (15-10) morpholinyl;   (15-11) phenoxy;   (15-12) pyrazolyl;   (15-13) thienyl; and   (15-14) N-oxide;
 
(16) pyrimidinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(17) pyridazinyl;
 
(18) pyrazinyl optionally substituted with one or more phenyl lower alkoxys;
 
(19) imidazo[2,1-b]thiazolyl optionally substituted with one or more halogens;
 
(20) thieno[2,3-b]pyrazinyl;
 
(21) 2,3-dihydroimidazo[2,1-b]thiazolyl optionally substituted with one or more phenyls;
 
(22) benzothiazolyl optionally substituted with one or more lower alkyls;
 
(23) indolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and halogen;
 
(24) imidazo[1,2-a]pyridyl or imidazo[1,5-a]pyridyl, each of which is optionally substituted with one or more lower alkyls;
 
(25) benzothienyl optionally substituted with one or more lower alkyls;
 
(26) benzimidazolyl optionally substituted with one or more lower alkyls;
 
(27) 2,3-dihydrobenzo[b]furyl;
 
(28) benzofuryl optionally substituted with one or more halogens;
 
(29) indazolyl optionally substituted with one or more lower alkyls;
 
(30) furo[2,3-c]pyridyl or 6,7-dihydrofuro[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl optionally substituted with lower alkoxy;
 
(31) furo[3,2-c]pyridyl or 4,5-dihydrofuro[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl optionally substituted with halogen or lower alkoxy, halogen, furyl, pyridyl and phenyl optionally substituted with one or more substituents selected from the group consisting of amino and lower alkoxy;
 
(32) thieno[2,3-c]pyridyl or 6,7-dihydrothieno[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo group and lower alkyl;
 
(33) thieno[3,2-c]pyridyl or 4,5-dihydrothieno[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(34) thieno[2,3-b]pyridyl;
 
(35) benzo[1,3]dioxolyl optionally substituted with one or more halogens;
 
(36) benzisoxazolyl;
 
(37) pyrazolo[2,3-a]pyridyl;
 
(38) indolizinyl;
 
(39) 2,3-dihydroindolyl optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl and lower alkanoyl;
 
(40) isoquinolyl or 1,2-dihydroisoquinolyl, each of which is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, halogen and oxo;
 
(41) 1,2,3,4-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(42) quinolyl optionally substituted with one or more substituents selected from the group consisting of amino optionally substituted with one or two lower alkyls, lower alkoxy, lower alkyl and oxo
 
(43) 1,2,3,4-tetrahydroquinolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, pyridyl lower alkyl, aralkyl (e.g., phenyl lower alkyl), lower alkoxy and oxo;
 
(44) 1,2-dihydroquinolyl optionally substituted with one or more substituents selected from the group consisting of amino optionally substituted with one or two lower alkyls, lower alkoxy, lower alkyl and oxo;
 
(45) chromanyl optionally substituted with one or more lower alkyls;
 
(46) 5,6,7,8-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(47) 3,4-dihydroisoquinolyl optionally substituted with one or more oxos;
 
(48) naphthyridinyl;
 
(49) 1,4-benzodioxanyl;
 
(50) cinnolinyl;
 
(51) quinoxalinyl;
 
(52) 2,3-dihydrobenz-1,4-oxazinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo;
 
(53) 2,3-dihydro-1H-benzo[d]imidazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo; and
   (54) piperidyl optionally substituted with one or more aryl carbonyls (e.g., phenyl carbonyl).       
 
         [0200]    Examples of more preferable substituents represented by R 6  and R 7  include the following substituents (1), (4a), (6a), (7a), (8a), (9a), (10a), (11a), (12a), (15a), (16a), (17), (18), (23a), (24a), (24b), (26), (29), (30a), (30b), (31a), (31b), (32a), (32b), (33a), (33b), (35a), (40a), (40b), (42a), (43a), (44a), and (53): 
         [0000]    (1) hydrogen;
 
(4a) phenyl optionally substituted with one or more substituents selected from the group consisting of the following (4-1), (4-2), (4a-4), (4a-5), (4-10), (4a-16), (4-18), (4-19), (4-23), (4-26) and (4-27):
       (4-1) cyano;   (4-2) hydroxyl;   (4a-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, 2-oxo-1,2,3,4-tetrahydroquinolyl, lower alkoxy, imidazolyl and morpholinyl;   (4a-5) lower alkoxy;   (4-10) pyrazolyl optionally substituted with one or more lower alkyls;   (4a-16) amino optionally substituted with one or more lower alkylsulfonyls;   (4-18) triazolyl   (4-19) imidazolyl;   (4-23) nitro;   (4-26) lower alkanoyl; and   (4-27) morpholinyl;
 
(6a) furyl optionally substituted with one or more lower alkyls optionally substituted with halogen;
 
(7a) thienyl optionally substituted with one or more lower alkyls; (8a) imidazolyl optionally substituted with one or more lower alkyls; (9a) pyrazolyl optionally substituted with one or more lower alkyls optionally substituted with lower alkoxy;
 
(10a) oxazolyl optionally substituted with one or more lower alkyls;
 
(11a) isoxazolyl optionally substituted with one or more lower alkyls;
 
(12a) thiazolyl optionally substituted with one or more lower alkyls optionally substituted with halogen;
 
(15a) pyridyl optionally substituted with one or more substituents selected from the group consisting of the following (15-1) to (15-5), (15a-7), (15-9), (15-11), (15-12) and (15-14):
   (15-1) halogen;   (15-2) cyano;   (15-3) amino optionally substituted with one or more substituents selected from the group consisting of lower alkanoyl and lower alkylsulfonyl;   (15-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, lower alkoxy, lower alkanoyloxy, cyclo lower alkyl amino, lower alkyl amino, lower alkanoyl amino, hydroxyl and pyrrolidinyl optionally substituted with one or more hydroxyls;   (15-5) oxo;   (15a-7) lower alkoxy;   (15-9) lower alkanoyl;   (15-11) phenoxy;   (15-12) pyrazolyl; and   (15-14) N-oxide;
 
(16a) pyrimidinyl optionally substituted with one or more lower alkyls;
 
(17) pyridazinyl;
 
(18) pyrazinyl optionally substituted with one or more phenyl lower alkoxys;
 
(23a) indolyl optionally substituted with one or more lower alkyls;
 
(24a) imidazo[1,2-a]pyridyl;
 
(24b) imidazo[1,5-a]pyridyl optionally substituted with one or more lower alkyls;
 
(26) benzimidazolyl optionally substituted with one or more lower alkyls;
 
(29) indazolyl optionally substituted with one or more lower alkyls;
 
(30a) furo[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(30b) 6,7-dihydrofuro[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(31a) furo[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(31b) 4,5-dihydrofuro[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl optionally substituted with halogen or lower alkoxy;
 
(32a) thieno[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(32b) 6,7-dihydrothieno[2,3-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo group and lower alkyl;
 
(33a) thieno[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(33b) 4,5-dihydrothieno[3,2-c]pyridyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(35a) benzo[1,3]dioxolyl;
 
(40a) isoquinolyl optionally substituted with one or more oxos;
 
(40b) 1,2-dihydroisoquinolyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(42a) quinolyl optionally substituted with one or more oxos;
 
(43a) 1,2,3,4-tetrahydroquinolyl optionally substituted with one or more substituents selected from the group consisting of aralkyl (e.g., phenyl lower alkyl), pyridyl lower alkyl and oxo;
 
(44a) 1,2-dihydroquinolyl optionally substituted with one or more oxos; and
 
(53) 2,3-dihydrobenzo[d]imidazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo.
       
 
         [0222]    Preferred embodiments of the diazepine compound of Formula (1) are described below. 
         [0000]    R 1 , R 2 , R 3  and R 4  are each independently hydrogen, lower alkyl, cyclo lower alkyl or lower alkoxy lower alkyl, and preferably hydrogen, C 1-6  alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl and sec-butyl), C 1-6  cyclo alkyl (e.g., cyclopropyl, cyclopropylmethyl, cyclopentyl and cyclohexyl), or C 1-6  alkoxy C 1-6  alkyl (e.g., 2-methoxyethyl and 2-ethoxyethyl). 
       Both Y 1  and Y 2  are —C═. 
       [0223]    A 1  is lower alkylene, and preferably C 1-6  alkylene such as methylene, ethylene, trimethylene, or tetramethylene. X A  and X B  are each independently lower alkylene, which is preferably C 1-6  alkylene such as methylene, ethylene, trimethylene, or tetramethylene; a bond; —CO—; or —SO 2 —. 
         [0224]    R 6  and R 7  are each independently a group selected from (1), (4a), (6a), (7a), (8a), (9a), (10a), (11a), (12a), (15a), (16a), (17), (18), (23a), (24a), (24b), (26), (29), (30b), (31b), (32b), (33b), (35a), (40b), (42a), (43a), (44a), and (53): 
         [0225]    Examples of X A  and X B  include a bond, lower alkylene, lower alkenylene, —CO—, —SO 2 —, -lower alkylene-SO 2 —, -lower alkylene-CO—, -lower alkenylene-CO—, -lower alkylene-CO—N(lower alkyl)-lower alkylene-, —N(lower alkyl)-lower alkylene-, —CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-, —N(phenyl lower alkyl)-lower alkylene-, —CO-lower alkylene-CO—, —CO—NH-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-O—, -lower alkylene-NH-lower alkylene-, -lower alkylene-SO 2 —NH-lower alkylene-, —N(lower alkyl)-CO-lower alkylene-, —N(lower alkyl)-lower alkylene-CO—, —N(lower alkyl)-lower alkylene-N(lower alkyl)-lower alkylene-, —N(phenyl)-lower alkylene-CO—, —N(phenyl)-lower alkylene-CO—, —NH—CO—, —NH—CO-lower alkylene-, —NH-lower alkylene-, —O-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-CO—, —NH-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —S-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —SO 2 —N(lower alkyl)-lower alkylene-, —SO 2 —NH-lower alkylene-, -lower alkenylene-CO—N(lower alkyl)-lower alkylene-, lower alkylene-N(phenyl lower alkyl)-lower alkylene-, —N(phenyl lower alkyl)-lower alkylene-, —N(phenyl)-lower al kylene-CO—N(lower alkyl)-lower alkylene-, and —CO-lower alkylene-O—CO-lower alkylene-O—. 
         [0226]    Preferred examples of X A  and X B  include a bond, lower alkylene, lower alkenylene, —CO—, —SO 2 —, -lower alkylene-SO 2 —, -lower alkylene-CO—, -lower alkenylene-CO—, -lower alkylene-CO—N(lower alkyl)-lower alkylene-, —N(lower alkyl)-lower alkylene-, —CO—N(lower alkyl)-lower alkylene-, and —O-lower alkylene-. 
         [0227]    Either of the two bonds in X A  may be bonded to R 1  or N, and either of the two bonds in X B  may be bonded to R 2  or N. 
         [0228]    The ring formed when R 6  and R 7  are linked together with the neighboring group —X A —N—X B — is a nitrogen-containing heterocyclic group optionally having one or more substituents. Examples of the nitrogen-containing heterocyclic group include the above-mentioned heterocyclic groups (a) to (c), (f) to (j), and (m) to (n). Examples of substituents of the nitrogen-containing heterocyclic group optionally having one or more substituents include the above-mentioned substituents (h1) to (h20). 
         [0229]    The diazepine compound of the present invention represented by Formula (1) or its salt can be readily produced by persons skilled in the art using technical knowledge, based on the Examples and Reference Examples of the present specification. For example, the diazepine compound or its salt can be produced according to the processes shown in the following reaction formulae. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , Y 1  and Y 2  are the same as above, and is a leaving group. 
         [0230]    The reaction of the compound of Formula (2) with the compound of Formula (3) can be performed in a general inert solvent or without using any solvent, in the presence or absence of a basic compound and/or catalyst. 
         [0231]    Examples of the leaving groups represented by X 1  include halogen atoms (e.g., chlorine, bromine, iodine, and like atoms), lower alkane sulfonyloxy (e.g., methanesulfonyloxy), halo substituted lower alkane sulfonyloxy (e.g., trifluoromethanesulfonyloxy), arylene sulfonyloxy (e.g., p-toluenesulfonyloxy, benzenesulfonyloxy), etc. 
         [0232]    Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower (C 1-6 ) alcohols such as methanol, ethanol, and isopropanol; ketones such as acetone and methyl ethyl ketone; polar solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide, and acetonitrile; and mixtures thereof. 
         [0233]    A wide variety of known basic compounds can be used as the basic compound. Examples of such basic compounds include inorganic bases, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, lithium hydrogencarbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; alkali metals such as sodium and potassium; sodium amide; sodium hydride; and potassium hydride; and organic bases, for example, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, and potassium ethoxide; triethylamine; tripropylamine; pyridine; quinoline; 1,5-diazabicyclo[4.3.0]non-5-ene (DBN); 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds can be used singly or in a combination of two or more. 
         [0234]    Examples of the catalyst include palladium compounds such as palladium acetate, bis(tributyltin)/bis(dibenzylideneacetone) palladium, copper iodide/2,2′-bipyridyl, bis(dibenzylideneacetone) palladium, copper iodide/bis(triphenylphosphine) palladium dichloride, tris(dibenzylideneacetone)dipalladium, R-tris (dibenzylideneacetone)-dipalladium, S-tris(dibenzylideneacetone) dipalladium, palladium(II) acetate, [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), and tetrakis(triphenylphosphine) palladium. 
         [0235]    Additives (ligands etc.) can be used together with the catalyst. Examples of the additive include compounds such as R-2,2′-bis diphenylphosphino)-1,1′-binaphthyl (R-BINAP), S-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (S-BINAP), RAC-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (RAC-BINAP), and 2,2-bis(diphenylimidazolidinyliden), xanthene compounds such as 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and borates such as tri-tert-butylphosphine tetrafluoroborate, and a mixture thereof. 
         [0236]    The above reaction may be performed by adding to the reaction system, as required, an alkali metal iodide serving as a reaction accelerator, such as potassium iodide or sodium iodide. 
         [0237]    The compound of Formula (3) is typically used in an amount of at least 0.5 moles, and preferably about 0.5 to about 10 moles, per mole of the compound of Formula (2). 
         [0238]    The amount of basic compound is typically 0.5 to 10 moles, and preferably 0.5 to 6 moles, per mole of the compound of Formula (2). 
         [0239]    The catalyst is appropriately used in a typical catalytic amount, preferably 0.0001 to 1 moles, and more preferably 0.001 to 0.5 moles, per mole of the compound (2). 
         [0240]    The reaction is typically performed at a temperature of 0 to 250° C., and preferably 0 to 200° C., and is typically completed in about 1 to about 80 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 9 , and Y 2  are the same as above. 
         [0241]    The reaction converting the compound of Formula (4) to the compound of Formula (1a) can be performed by catalytic reduction of the compound of Formula (4) in a suitable solvent, in the presence of a catalytic hydrogenation reducing agent. 
         [0242]    The solvent is not limited as long as it does not adversely affect the reduction reaction. Examples of such solvents include carboxylic acids such as formic acid and acetic acid; ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; and lower (e.g., C 1-6 ) alcohols such as methanol, ethanol, and isopropanol. 
         [0243]    Examples of catalytic hydrogenation reducing agents include palladium black, palladium carbon, platinum oxide, platinum black, and Raney nickel. 
         [0244]    The amount of catalytic hydrogenation reducing agent is typically 0.1 to 40 wt %, and preferably 1 to 20 wt %, based on the compound of Formula (4). 
         [0245]    The reaction can be typically performed in a hydrogen atmosphere at atmospheric pressure to about 20 atm, and preferably atmospheric pressure to 10 atm; or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate. The reaction temperature may typically be about −30 to about 100° C., and preferably about 0 to about 60° C. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , Y 1  and Y 2  are the same as above; and R 8  is lower alkyl. 
         [0246]    The reaction converting the compound of Formula (5) to the compound of Formula (6) can be performed in a general inert solvent or without using any solvent, in the presence of an azide compound, a basic compound, and a lower (C 1-6 ) alcohol (R 8 OH). 
         [0247]    Examples of “lower alkyl” represented by R 8  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, and tert-butyl, with tert-butyl being preferred. 
         [0248]    Examples of inert solvents include ethers such as dioxane, tetrahydrofuran, diethylether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; and mixtures thereof. 
         [0249]    Examples of azide compounds include sodium azide, lithium azide, and diphenylphosphoryl azide (DPPA). 
         [0250]    Examples of usable basic compounds include organic bases such as triethylamine; tripropylamine; diisopropylethylamine; pyridine; quinoline; 1,5-diazabicyclo[4.3.0]non-5-ene (DBN); 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); and 1,4-diazabicyclo[2.2.2]octane (DABCO). 
         [0251]    The reaction temperature is not limited, and the reaction is usually carried out under conventional conditions. 
         [0252]    In the reaction, a carboxylic azide is produced from the carboxylic compound of Formula (5) and an azide compound, and the carboxylic azide undergoes subsequent Curtius rearrangement to produce an isocyanate. The isocyanate reacts with a lower (C 1-6 ) alcohol (R 8 OH) to produce a urethane compound of Formula (6). 
         [0253]    Next, the reaction converting the compound of Formula (6) to the compound of Formula (1b) can be performed by solvolysis in a suitable solvent, in the presence of an acid or basic compound. 
         [0254]    Examples of usable solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, and tert-butanol; ketones such as acetone and methyl ethyl ketone; ethers such as diethylether, dioxane, tetrahydrofuran, monoglyme, and diglyme; aliphatic acids such as acetic acid and formic acid; esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; dimethyl sulfoxide, N,N-dimethylformamide, hexamethylphosphorictriamide, and mixtures thereof. 
         [0255]    Examples of acids include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; and organic acids such as formic acid, acetic acid, thioglycolic acid, trifluoroacetic acid, and sulfonic acids such as p-toluenesulfonic acid. These acids may be used singly or in a combination of two or more. 
         [0256]    Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. These basic compounds can be used singly or in a combination of two or more. 
         [0257]    The amount of acid or basic compound is typically at least 1 mole, and preferably about 1 to about 10 moles, per mole of the compound of Formula (6). 
         [0258]    The solvolysis reaction (particularly the hydrolysis) advantageously proceeds typically at about 0 to about 200° C., and preferably at about 0 to about 150° C., and is typically completed in about 10 minutes to about 80 hours. 
         [0259]    Particularly when R 8  is tert-butyl, the solvolysis can be easily accomplished using the above-mentioned acids (particularly hydrochloric acid and the like) to produce the compound of Formula (1b). 
         [0260]    Alternatively, the compound of Formula (5) can be directly converted to the compound of Formula (1b). This reaction can be performed by reacting the compound (5) with an azide compound in a general inert solvent or without using any solvent, in the presence of a basic compound, followed by treating the product with water. In this reaction, an isocyanate is produced from the above-mentioned carboxylic compound of Formula (5) and azide compound, and the isocyanate is hydrolyzed to produce the amine compound of Formula (1b). 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , Y 1  and Y 2  are the same as above; and A 1a  is lower alkylene with 3 or more carbon atoms. 
         [0261]    Examples of “lower alkylene with 3 or more carbon atoms” represented by A 1a  include alkylene groups with 3 to 6 carbon atoms, such as trimethylene, tetramethylene, pentamethylene, and hexamethylene. 
         [0262]    The reaction converting the compound of Formula (7) to the compound of Formula (1c) can be performed by reacting the compound (7) with hydrazine in a suitable solvent, or by hydrolysis. Here, hydrazine hydrate may be used as the hydrazine. 
         [0263]    Examples of solvents used in reacting the hydrazine include water; halogenated hydrocarbons such as chloroform, dichloromethane, and dichloroethane; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane; esters such as methyl acetate and ethyl acetate; aprotic polar solvents such as N,N-dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric triamide; alcohols such as methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve; acetonitrile; pyridine; and mixtures thereof. 
         [0264]    The amount of hydrazine is typically at least about 1 mole, and preferably about 1 to about 5 moles, per mole of the compound of Formula (7). 
         [0265]    The reaction is performed typically at about 0 to about 120° C., and preferably at about 0 to about 100° C., and is typically completed in about 0.5 to about 5 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , X A , A 1 , Y 1  and Y 2  are the same as above;
 
and R 7a  is hydrogen or lower alkyl.
 
Examples of “lower alkyl” represented by R 7a  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, n-hexyl, isohexyl, and 3-methylpentyl.
 
         [0266]    The reaction between the compound of Formula (1d) and the compound of Formula (8) is performed, for example, in a suitable solvent or without using any solvent, in the presence of a reducing agent. 
         [0267]    Examples of usable solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol; aliphatic acids such as formic acid, and acetic acid; ethers such as diethylether, tetrahydrofuran, dioxane, monoglyme, and diglyme; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; acetonitrile; and mixtures thereof. 
         [0268]    Examples of reducing agents include aliphatic acids such as formic acid; aliphatic acid alkali metal salts such as sodium formate; hydride reducing agents such as sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, sodium trimethoxyborohydride, lithium aluminium hydride, and mixtures thereof, or mixtures of aliphatic acids or aliphatic acid alkali metal salts with hydride reducing agents; and catalytic hydrogenation reducing agents such as palladium black, palladium carbon, platinum oxide, platinum black, and Raney nickel. 
         [0269]    When an aliphatic acid such as formic acid, or an aliphatic acid alkali metal salt such as sodium formate is used as a reducing agent, a suitable reaction temperature is typically about room temperature to about 200° C., and preferably about 50 to about 150° C. The reaction is typically completed in about 10 minutes to about 10 hours. Preferably, the aliphatic acid or aliphatic acid alkali metal salt is used in large excess relative to the compound of Formula (1d). 
         [0270]    When a hydride reducing agent is used, a suitable reaction temperature is typically about −80 to about 100° C., and preferably about −80 to about 70° C. The reaction is typically completed in about 30 minutes to about 60 hours. The hydride reducing agent is typically used in an amount of about 1 to about 20 moles, and preferably about 1 to about 10 moles, per mole of the compound of Formula (1d). Particularly when lithium aluminium hydride is used as a hydride reducing agent, it is preferable to use as a solvent an ether such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, or diglyme; or an aromatic hydrocarbon such as benzene, toluene, or xylene. To the reaction system may be added an amine such as trimethylamine, triethylamine, or N-ethyldiisopropylamine; or a molecular sieve such as molecular sieve 3A (MS-3A) or molecular sieve 4A (MS-4A). 
         [0271]    When a catalytic hydrogenation reducing agent is used, the reaction is typically performed at about −30 to about 100° C., and preferably at about 0 to about 60° C., in a hydrogen atmosphere at typically about atmospheric pressure to about 20 atm, and preferably at about atmospheric pressure to about 10 atm, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate. The reaction is typically completed in about 1 to about 12 hours. The catalytic hydrogenation reducing agent is typically used in an amount of about 0.1 to about 40 wt %, and preferably about 1 to about 20 wt %, based on the compound of Formula (1d). 
         [0272]    In the reaction of the compound of Formula (1d) and the compound of Formula (8), the compound of Formula (8) is typically used in an amount of at least 1 mole, and preferably 1 to 5 moles, per mole of the compound of Formula (1d). 
         [0273]    The compound of Formula (8) may also be a hydrated compound wherein a water molecule is attached to a carbonyl group. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , X A , X B , A 1 , X 1 , Y 1  and Y 2  are the same as above. 
         [0274]    The reaction of the compound of Formula (1d) with the compound of Formula (9) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0275]    Alternatively, the reaction of the compound of Formula (1d) with the compound of Formula (9) can be performed by the known “Ullmann condensation” etc. The reaction can be preferably adopted especially when X B  is a bond and R 7  is aryl or heterocyclic (especially unsaturated heterocyclic) group optionally substituted. For example, the reaction can be carried out in a solvent (e.g., toluene, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP) and dimethyl sulfoxide (DMSO)), in the presence of copper compound (e.g., copper oxides, copper halides such as copper iodide), a basic compound (e.g., sodium tert-butoxide, K3PO4 and Cs2CO3), and if necessary a phosphine (e.g., triphenylphosphine, xantphos, tri-tert-butylphosphine, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl(BINAP), tetrafluoroborate, N,N′-dimethylethylenediamine, and L-proline). 
         [0276]    The reaction temperature is not limited, and the reaction is usually carried out at ambient temperature, under warming or under heating. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 5 , Y 1  and Y 2  are the same as above. 
         [0277]    The reaction of the compound of Formula (10) with the compound of Formula (3) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (1d) with the compound of Formula (8) shown in Reaction Formula 5 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , R 3 , R 4 , R 5 , A 1 , X 1 , Y 1  and Y 2  are the same as above; and R 1a  is lower alkyl. 
         [0278]    Examples of “lower alkyl” represented by R 1a  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and sec-butyl. 
         [0279]    The reaction of the compound of Formula (1g) with the compound of Formula (11) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0280]    In this reaction, when R 4  is hydrogen in the compound of Formula (1g), a compound may be obtained wherein the 1- and 5-positions of the benzodiazepine skeleton are simultaneously replaced by the group R 1a . 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1a , R 4 , R 5 , A 1 , Y 1  and Y 2  are the same as above. 
         [0281]    The reaction of the compound of Formula (1i) with the compound of Formula (11) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0282]    In this reaction, when R 4  is hydrogen in the compound of Formula (1i), a compound may be obtained wherein the 1-, 3-, and 5-positions of the benzodiazepine skeleton are simultaneously replaced by the group R 1a . 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 4 , R 5 , A 1 , X 1 , Y 1  and Y 2  are the same as above; and R 2a  is lower alkyl. 
         [0283]    Examples of “lower alkyl” represented by R 2a  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and sec-butyl. 
         [0284]    The reaction of the compound of Formula (1k) with the compound of Formula (11) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0285]    In this reaction, when R 1  and/or R 4  is hydrogen in the compound of Formula (1k), a compound may be obtained wherein the 1-, 3-, and 5-positions of the benzodiazepine skeleton are simultaneously replaced by the group R 2a . 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , R 3 , R 4 , R 1a , X 1 , Y 1  and Y 2  are the same as above;
 
R 9  is lower alkoxy; and R 10  is lower alkoxycarbonyl.
 
         [0286]    Examples of “lower alkoxy” represented by R 9  include linear or branched alkoxy groups with 1 to 6 carbon atoms, such as methoxy, and ethoxy. Examples of “lower alkoxycarbonyl” represented by R 10  include (C 1-6  alkoxy) carbonyl groups, such as methoxycarbonyl, ethoxycarbonyl. 
         [0287]    In the reaction of the compound of Formula (13) with the compound of Formula (14), the compound of Formula (13) is reacted with the carboxylic acid compound of Formula (14) through a general amide bond formation reaction. Conditions for known amide bond formation reactions can be easily employed in this amide formation reaction. For example, the following reaction methods can be employed: (i) a mixed acid anhydride method, in which Carboxylic Acid (14) is reacted with an alkyl halocarboxylate to form a mixed acid anhydride, which is then reacted with Amine (13); (ii) an active ester method, in which Carboxylic Acid (14) is converted to an activated ester such as a phenyl ester, p-nitrophenyl ester, N-hydroxysuccinimide ester, or 1-hydroxybenzotriazole ester, or to an activated amide with benzoxazoline-2-thione, and the activated ester or amide is reacted with Amine (13); (iii) a carbodiimide method, in which Carboxylic Acid (14) is subjected to a condensation reaction with Amine (13) in the presence of an activating agent such as dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC), or carbonyldiimidazole; and (iv) other methods, for example, a method in which Carboxylic Acid (14) is converted to a carboxylic anhydride using a dehydrating agent such as acetic anhydride, and the carboxylic anhydride is reacted with Amine (13), a method in which an ester of Carboxylic Acid (14) with a lower (C 1-6 ) alcohol is reacted with Amine (13) at a high pressure and a high temperature, and a method in which an acid halide of Carboxylic Acid (14), a carboxylic acid halide, is reacted with Amine (13). 
         [0288]    Generally, the mixed acid anhydride method(i) is performed in a solvent, in the presence or absence of a basic compound. Any solvents used for conventional mixed acid anhydride methods are usable. Specific examples of usable solvents include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane; esters such as methyl acetate, ethyl acetate, and isopropyl acetate; aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, and hexamethylphosphoric triamide; and mixtures thereof. 
         [0289]    Examples of usable basic compounds include organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO); inorganic bases, for example, carbonates such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide; potassium hydride; sodium hydride; potassium; sodium; sodium amide; and metal alcoholates such as sodium methylate and sodium ethylate. 
         [0290]    Examples of alkyl halocarboxylates usable in the mixed acid anhydride method include methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, and isobutyl chloroformate. In this method, Carboxylic Acid (14), an alkyl halocarboxylate, and Amine (13) are preferably used in equimolar amounts, but each of the alkyl halocarboxylate and Carboxylic Acid (14) can also be used in an amount of about 1 to about 1.5 moles per mole of Amine (13). 
         [0291]    The reaction is typically performed at about −20 to about 150° C., and preferably at about 10 to about 50° C., typically for about 5 minutes to about 30 hours, and preferably for about 5 minutes to about 25 hours. 
         [0292]    Method (iii), in which a condensation reaction is performed in the presence of an activating agent, can be performed in a suitable solvent in the presence or absence of a basic compound. Solvents and basic compounds usable in this method include those mentioned hereinafter as solvents and basic compounds usable in the method in which a carboxylic acid halide is reacted with Amine (13) mentioned above as one of the other methods (iv). A suitable amount of activating agent is typically at least 1 mole, and preferably 1 to 5 moles per mole of Compound (13). When WSC is used as an activating agent, the addition of 1-hydroxybenzotriazol to the reaction system allows the reaction to proceed advantageously. The reaction is typically performed at about −20 to about 180° C., and preferably at about 0 to about 150° C., and is typically completed in about 5 minutes to about 90 hours. 
         [0293]    When the method in which a carboxylic acid halide is reacted with Amine (13), mentioned above as one of the other methods (iv), is employed, the reaction is performed in the presence of a basic compound in a suitable solvent. Examples of usable basic compounds include a wide variety of known basic compounds, such as those for use in the Schotten-Baumann reaction described above. In addition to those usable in the mixed acid anhydride method, usable solvents include alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve; acetonitrile; pyridine; acetone; and water. The ratio of the carboxylic acid halide to Amine (13) is not limited, and can be suitably selected from a wide range. It is typically suitable to use, for example, at least about 1 mole, and preferably about 1 to about 5 moles of the carboxylic acid halide per mole of Amine (13). The reaction is typically performed at about −20 to about 180° C., and preferably at about 0 to about 150° C., and is typically completed in about 5 minutes to about 30 hours. 
         [0294]    The amide bond formation reaction shown in Reaction Formula 11 can also be performed by reacting Carboxylic Acid (14) with Amine (13) in the presence of a phosphorus compound serving as a condensing agent, such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric azide, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, or the like. 
         [0295]    The reaction is performed in the presence of a solvent and a basic Compound usable for the method in which a carboxylic acid halide is reacted with Amine (13), typically at about −20 to about 150° C., and preferably at about 0 to about 100° C., and is typically completed in about 5 minutes to about 30 hours. It is suitable to use each of the condensing agent and Carboxylic Acid (14) in amounts of at least about 1 mole, and preferably about 1 to about 2 moles, per mole of Amine (13). 
         [0296]    The reaction converting the compound of Formula (15) to the compound of Formula (16) can be performed by, for example, [1] reducing the compound of Formula (15) in a suitable solvent using a catalytic hydrogenation reducing agent, or [2] reducing the compound of Formula (15) in a suitable inert solvent using a reducing agent such as a mixture of an acid with a metal or metal salt, a mixture of a metal or metal salt with an alkali metal hydroxide, sulfide, or ammonium salt. 
         [0297]    When Method [1] in which a catalytic hydrogenation reducing agent is used, examples of usable solvents are water; acetic acid; alcohols such as methanol, ethanol and isopropanol; hydrocarbons such as n-hexane and cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether and diethylene glycol dimethyl ether; esters such as ethyl acetate and methyl acetate; aprotic polar solvents such as N,N-dimethylformamide; and mixtures thereof. Examples of usable catalytic hydrogenation reducing agents include palladium, palladium black, palladium carbon, platinum carbon, platinum, platinum black, platinum oxide, copper chromite, and Raney nickel. The reducing agent is typically used in an amount of about 0.02 times to about equal to the weight of the compound of Formula (15). The reaction temperature is typically about −20 to about 150° C., and preferably about 0 to about 100° C. The hydrogen pressure is typically about 1 to 10 atm. The reaction is typically completed in about 0.5 to about 100 hours. An acid such as hydrochloric acid may be added to the reaction. 
         [0298]    When Method [2] above is used, a mixture of iron, zinc, tin, or tin (II) chloride, with a mineral acid such as hydrochloric acid or sulfuric acid; or a mixture of iron, iron (II) sulfate, zinc, or tin, with an alkali metal hydroxide such as sodium hydroxide, a sulfide such as ammonium sulfide, aqueous ammonia solution, or an ammonium salt such as ammonium chloride, can be used as a reducing agent. Examples of inert solvents are water; acetic acid; alcohols such as methanol and ethanol; ethers such as dioxane; and mixtures thereof. Conditions for the reduction reaction can be suitably selected according to the reducing agent to be used. For example, when a mixture of tin (II) chloride and hydrochloric acid is used as a reducing agent, the reaction is advantageously performed at about 0 to about 150° C. for about 0.5 to about 10 hours. A reducing agent is used in an amount of at least 1 mole, and preferably about 1 to 5 moles, per mole of the compound of Formula (15). 
         [0299]    The reaction converting the compound of Formula (16) to the compound of Formula (17) is performed under the same reaction conditions as those for the reaction of the compound of Formula (13) with the compound of Formula (14). 
         [0300]    The reaction of the compound of Formula (17) with the compound of Formula (11) is performed under the same reaction conditions as those for the reaction of the compound of Formula (1g) with the compound of Formula (11) in Reaction Formula 8. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2a , R 4 , R 9 , and Y 2  are the same as above. 
         [0301]    The reaction of the compound of Formula (19) with the compound of Formula (12) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0302]    When R 1  and/or R 4  is hydrogen in the reaction of the compound of Formula (19) with the compound of Formula (12), the hydrogen atom may be replaced with R 2a . 
         [0303]    The compound of Formula (18) can also be produced according to the process shown in the following Reaction Formula 13. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 9 , Y 1  and Y 2  are the same as above. 
         [0304]    The reaction of the compound of Formula (20) with the compound of Formula (21) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (13) with the compound of Formula (14) shown in Reaction Formula 11 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 9 , Y 1  and Y 2  are the same as above; and Tf is trifluoromethanesulfonyl (CF 3 SO 2 —). 
         [0305]    The reaction converting the compound of Formula (18) to the compound of Formula (22) can be performed in a suitable solvent in the presence of an acid. 
         [0306]    Examples of solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, and isopropanol; ethers such as dioxane, tetrahydrofuran, and diethylether; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; polar solvents such as acetonitrile; and mixtures thereof. Examples of acids include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; aliphatic acids such as formic acid and acetic acid; sulfonic acids such as p-toluenesulfonic acid; Lewis acids such as boron fluoride, aluminium chloride, and boron tribromide; iodides such as sodium iodide and potassium iodide; and mixtures of these iodides and Lewis acids. 
         [0307]    The reaction is performed typically at about 0 to about 200° C., and preferably at about 0 to about 150° C., and is typically completed in about 0.5 to about 25 hours. The amount of acid is typically about 1 to about 10 moles, and preferably about 1 to about 2 moles, per mole of the compound of Formula (18). 
         [0308]    The reaction converting the compound of Formula (22) to the compound of Formula (23) is performed by reacting the compound of Formula (22) with trifluoromethanesulfonic anhydride in a suitable solvent, in the presence or absence of a basic compound. 
         [0309]    Examples of solvents include ethers such as dioxane, tetrahydrofuran, and diethylether; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; polar solvents such as acetonitrile; and mixtures thereof. Examples of basic compounds include organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO). 
         [0000]    The reaction temperature is not limited, and the reaction is usually carried out under conventional conditions. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , Tf, Y 1  and Y 2  are the same as above; M is a metal, for example, Na, K, Ag, Zu, Cu, and the like; and X is a positive number. 
         [0310]    The reaction converting the compound of Formula (23) to the compound of Formula (4) can be performed by reacting the compound of Formula (23) with a cyano metal in a suitable solvent, in the presence of a catalyst. 
         [0311]    Examples of metal cyanides (M(CN) x ) include sodium cyanide, potassium cyanide, silver cyanide, zinc cyanide, and cuprous cyanide. 
         [0312]    Examples of solvents usable in this reaction include water; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethylether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol; aliphatic acids such as acetic acid; esters such as ethyl acetate and methyl acetate; ketones such as acetone and methyl ethyl ketone; acetonitrile; pyridine; dimethyl sulfoxide; N,N-dimethylformamide; hexamethylphosphoric triamide; and mixtures thereof. 
         [0313]    Examples of catalysts include palladium compounds such as tetrakis(triphenylphosphine) palladium (0); dichlorobis(triphenylphosphine) palladium (II); and tris(dibenzylideneacetone)dipalladium (0). 
         [0314]    A ligand such as 1,1′-bis(diphenylphosphino) ferrocene or zinc dust may be added, as required, in order to promote the reaction. 
         [0315]    The catalyst can be typically used in an amount of 0.01 to 1 mole, and preferably 0.01 to 0.5 moles, per mole of the compound of Formula (23). 
         [0316]    The metal cyanide can be typically used in an amount of at least 1 mole, and preferably 1 to 3 moles, per mole of the compound of Formula (23). 
         [0317]    The reaction is typically performed at room temperature to 200° C., and preferably at about room temperature to about 150° C. The reaction is typically completed in about 1 hour to about 1 week. 
         [0318]    The reaction converting the compound of Formula (4) to the compound of Formula (10) is performed in a suitable solvent, in the presence of a reducing agent. 
         [0319]    Examples of solvents include aliphatic acids such as formic acid; ethers such as dioxane, tetrahydrofuran, diethylether, and diethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; and mixtures thereof. 
         [0320]    Examples of reducing agents include alkylaluminum hydrides such as diisobutylaluminum hydride; and Raney nickel. The reducing agent is typically used in an amount at least equal to, and preferably from an equal weight to 5 times the weight of the compound of Formula (4). 
         [0321]    The reaction is typically performed at room temperature to 200° C., and preferably at about room temperature to about 150° C. The reaction is typically completed in about 0.5 to about 20 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , Tf, Y 1  and Y 2  are the same as above; and is lower alkyl. 
         [0322]    Examples of “lower alkyl” represented by R II  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, and ethyl. 
         [0323]    The reaction converting the compound of Formula (23) and the compound of Formula (24) to the compound of Formula (25) can be performed in a suitable solvent, in the presence of a catalyst. 
         [0324]    Examples of usable solvents include water; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethylether, tetrahydrofuran, dioxane, 2-methoxyethanol, monoglyme, and diglyme; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol; aliphatic acids such as acetic acid; esters such as ethyl acetate and methyl acetate; ketones such as acetone and methyl ethyl ketone; acetonitrile; pyridine; dimethyl sulfoxide; N,N-dimethylformamide; hexamethylphosphorictriamide; and mixtures thereof. 
         [0325]    Preferable as the catalyst are palladium compounds, for example, tetrakis(triphenylphosphine)palladium (0); dichlorobis(triphenylphosphine)palladium (II); and the like. The catalyst is typically used in an amount of about 0.01 to about 1 mole, and preferably about 0.01 to about 0.5 moles, per mole of the compound of Formula (23). 
         [0326]    Further, a basic compound such as triethylamine, pyridine, may be added, as required. 
         [0327]    The reaction temperature is not limited, and the reaction is usually carried out under conventional conditions. 
         [0328]    The reaction converting the compound of Formula (25) to the compound of Formula (26) can be performed by catalytic reduction of the compound of Formula (25) in a suitable solvent in a hydrogen atmosphere. 
         [0329]    Known hydrogenolysis methods can be widely employed in hydrogenolysis. Examples of such hydrogenolysis methods include chemical reduction and catalytic reduction. 
         [0330]    Catalysts suitable for use in catalytic reduction include platinum catalysts, such as platinum plates, spongy platinum, platinum black, colloid platinum, platinum oxide, and platinum wires; palladium catalysts, such as spongy palladium, palladium black, palladium oxide, palladium carbon, palladium/barium sulfate, and palladium/barium carbonate; nickel catalysts, such as reduced nickel, nickel oxide, and Raney nickel; cobalt catalysts, such as reduced cobalt and Raney cobalt; and iron catalysts, such as reduced iron. 
         [0331]    The amount of the catalyst used for catalytic reduction is not limited, and may be an amount generally used. 
         [0332]    The reaction temperature is typically 0 to 120° C., preferably room temperature to about 100° C., and more preferably room temperature to 80° C. The reaction time is typically 30 minutes to 24 hours, preferably 30 minutes to 10 hours, and more preferably 30 minutes to 4 hours. 
         [0333]    The reaction converting the compound of Formula (26) to the compound of Formula (5) can be performed by hydrolysis of the compound (26). 
         [0334]    This hydrolytic reaction is performed in a suitable solvent or without any solvent, in the presence of an acid or basic compound. 
         [0335]    Examples of solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, and tert-butanol; ketones such as acetone and methyl ethyl ketone; ethers such as diethylether, dioxane, tetrahydrofuran, monoglyme, and diglyme; aliphatic acids such as acetic acid and formic acid; esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; dimethyl sulfoxide; N,N-dimethylformamide; hexamethylphosphoric triamide; and mixtures thereof. 
         [0336]    Examples of acids include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; and organic acids such as formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, and like sulfonic acids. These acids may be used singly or in a combination of two or more. 
         [0337]    Examples of basic compounds include carbonates such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; and metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and lithium hydroxide. These basic compounds can be used singly or in a combination of two or more. 
         [0338]    The hydrolytic reaction advantageously proceeds typically at about 0 to about 200° C., and preferably at about 0 to about 150° C. The reaction is typically completed in about 10 minutes to about 30 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , Tf, Y 1  and Y 2  are the same as above; and A 1b  is lower alkylene. 
         [0339]    Examples of “lower alkylene” represented by A 1b  include alkylene groups with 1 to 4 carbon atoms, such as methylene, ethylene, trimethylene, and tetramethylene. 
         [0340]    The reaction converting the compound of Formula (23) and the compound of Formula (27) to the compound of Formula (28) can be performed in a suitable solvent, in the presence of a copper halide and a palladium catalyst. 
         [0341]    Examples of solvents include ketones such as acetone and methyl ethyl ketone; ethers such as diethylether, dioxane, tetrahydrofuran, monoglyme, and diglyme; aliphatic acids such as acetic acid and formic acid; esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; dimethyl sulfoxide; N,N-dimethylformamide; hexamethylphosphoric triamide; and mixtures thereof. 
         [0342]    Examples of copper halides include copper (I) chloride, copper (I) bromide, and copper (I) iodide. 
         [0343]    Examples of palladium catalysts include palladium compounds such as tetrakis(triphenylphosphine)palladium (0); and dichlorobis(triphenylphosphine)palladium (II). 
         [0344]    A basic compound may be added, as required. Examples of basic compounds include triethylamine, diisopropylethylamine, pyridine, and diethylamine. The basic compound can be typically used in an amount of 0.01 to 10 mole, and preferably 0.01 to 1 moles, per mole of the compound of Formula (23). 
         [0345]    The reaction advantageously proceeds typically at about 0 to about 200° C., and preferably at about 0 to about 180° C. The reaction is typically completed in about 10 minutes to about 30 hours. 
         [0346]    The reaction converting the compound of Formula (28) to the compound of Formula (7) can be performed under the same reaction conditions as those for the reaction converting the compound of Formula (25) to the compound of Formula (26) shown in Reaction Formula 16 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 6 , R 7 , R 8 , X A , X B , and X 1  are the same as above. 
         [0347]    The reaction of the compound of Formula (3a) with the compound of Formula (8) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (1d) with the compound of Formula (8) shown in Reaction Formula 5 above. 
         [0348]    The reaction of the compound of Formula (3a) with the compound of Formula (9) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0349]    The compound of Formula (3), which is used as a starting material, can be easily prepared by the process shown in the following reaction formula. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 7b  is a nitrogen-containing heterocyclic group optionally having one or more substituents; and
 
X B1  is lower alkylene.
 
         [0350]    Examples of R 7b  include, among groups represented by the group R 7  mentioned above, groups obtained by removing hydrogen from saturated or unsaturated, monocyclic or polycyclic, heterocyclic compounds having an N—H bond, and groups optionally having one or more substituents. 
         [0351]    Examples of “lower alkylene” represented by X B1  include alkylene groups with 2 to 4 carbon atoms, such as ethylene and trimethylene. 
         [0352]    The reaction of the compound of Formula (29) with the compound of Formula (30) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) and the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0353]    The reaction converting the compound of Formula (31) to the compound of Formula (3d) can be performed under the same reaction conditions as those for the reaction converting the compound of Formula (7) to the compound of Formula (1c) shown in Reaction Formula 4 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 7b  is the same as above; X B2  is lower alkylene; and R 12  and R 13  are each independently lower alkyl, or R 12  and R 13  are linked to form lower alkylene. 
         [0354]    Examples of “lower alkyl” represented by R 12  and R 13  include linear or branched alkylene groups with 1 to 6 carbon atoms, such as methyl, ethyl, and n-propyl. Examples of “lower alkylene” formed by R 12  and R 13  when they are linked include alkylene groups with 1 to 4 carbon atoms, such as methylene, ethylene, trimethylene, and tetramethylene. 
         [0355]    Examples of “lower alkylene” represented by X B2  include alkylene groups with 1 to 6 carbon atoms, such as methylene, ethylene, trimethylene, and tetramethylene. 
         [0356]    The reaction of the compound of Formula (29) with the compound of Formula (32) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) and the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0357]    The reaction converting the compound of Formula (33) to the compound of Formula (8a) can be performed by hydrolysis of the compound (33). 
         [0358]    This hydrolytic reaction is performed in a suitable solvent or without any solvent, in the presence of an acidic compound. 
         [0359]    Examples of solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, and tert-butanol; ketones such as acetone and methyl ethyl ketone; ethers such as diethylether, dioxane, tetrahydrofuran, monoglyme, and diglyme; aliphatic acids such as acetic acid and formic acid; esters such as methyl acetate and ethyl acetate; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; dimethyl sulfoxide; N,N-dimethylformamide; hexamethylphosphoric triamide; and mixtures thereof. 
         [0360]    Examples of acids include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; and organic acids such as formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonic acid (PPTS), and like sulfonic acids. These acids may be used singly or in a combination of two or more. 
         [0361]    The hydrolytic reaction advantageously proceeds typically at about 0 to about 100° C., and preferably at about 0 to about 80° C. The reaction is typically completed in about 10 minutes to about 30 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein A 1b  is the same as above; and Ms is methanesulfonyl (CH 3 SO 2 —). 
         [0362]    The reaction converting the compound of Formula (34) to the compound of Formula (35) is performed by methanesulfonylation (mesylation) of the compound of Formula (34) using a conventional method. Typically, the compound of Formula (35) can be produced by reacting the compound of Formula (34) with trifluoromethanesulfonic anhydride in a suitable solvent (e.g., dichloromethane), in the presence of a basic compound (e.g., triethylamine). 
         [0363]    The reaction converting the compound of Formula (35) to the compound of Formula (36) is performed by iodination of the compound of Formula (35) with an iodinating agent such as sodium iodide, in a suitable solvent (e.g., acetone). 
         [0364]    The reaction converting the compound of Formula (36) to the compound of Formula (27) can be performed by reacting the compound of Formula (36) with potassium phthalimide in a suitable solvent (e.g., N,N-dimethylformamide). 
         [0365]    Alternatively, the compound of Formula (27) can be directly produced by reacting the compound of Formula (34) with phthalimide under the Mitsunobu reaction conditions (e.g., using diethyl azodicarboxylate (DEAD) and triphenylphosphine). 
         [0366]    The compound of Formula (1) according to the present invention and the starting materials thereof can be produced using a known or conventional synthetic method other than the production method described above. 
         [0367]    In addition, compounds in the form in which a solvate (for example, a hydrate, ethanolate, etc.) was added to the starting material compounds and object compounds shown in each of the reaction formulae are included in each of the formulae. 
         [0368]    The compound of Formula (1) according to the present invention includes stereoisomers and optical isomers. 
         [0369]    The starting material compounds and object compounds represented by each of the reaction formulae can be used in an appropriate salt form. 
         [0370]    Each of the object compounds obtained according to the above reaction formulae can be isolated and purified from the reaction mixture by, for example, after cooling the reaction mixture, performing an isolation procedure such as filtration, concentration, extraction, etc., to separate a crude reaction product, and then subjecting the crude reaction product to a general purification procedure such as column chromatography, recrystallization, etc. 
         [0371]    Among the compounds of the present invention, those having a basic group or groups can easily form salts with common pharmaceutically acceptable acids. Examples of such acids include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and other inorganic acids, methansulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malic acid, lactic acid and other organic acids, etc. 
         [0372]    Among the compounds of the present invention, those having an acidic group or groups can easily form salts by reacting with pharmaceutically acceptable basic compounds. Examples of such basic compounds include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, etc. 
         [0373]    In the compound of the present invention, one or more atoms can be substituted with one or more isotopic atoms. Examples of the isotopic atoms include deuterium ( 2 H), tritium ( 3 H),  13 C,  14 N,  18 O, etc. 
         [0374]    The following is an explanation of pharmaceutical preparations comprising the compound of the present invention as an active ingredient. 
         [0375]    Such pharmaceutical preparations are obtained by formulating the compound of the present invention into general pharmaceutical preparations, using typically employed diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, etc. 
         [0376]    The form of such pharmaceutical preparations can be selected from various forms according to the purpose of therapy. Typical examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.) and the like. 
         [0377]    To form tablets, any of various known carriers can be used, including, for example, lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose and other excipients; water, ethanol, propanol, simple syrup, glucose solutions, starch solutions, gelatin solutions, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone and other binders; dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogencarbonate, calcium carbonate, aliphatic acid esters of polyoxyethylenesorbitan, sodium laurylsulfate, stearic acid monoglyceride, starch, lactose and other disintegrants; white sugar, stearin, cacao butter, hydrogenated oils and other disintegration inhibitors; quaternary ammonium base, sodium lauryl sulfate and other absorption promoters; glycerin, starch and other wetting agents; starch, lactose, kaolin, bentonite, colloidal silicic acid and other adsorbents; purified talc, stearates, boric acid powder, polyethylene glycol and other lubricants; etc. 
         [0378]    Such tablets may be coated with general coating materials as required, to prepare, for example, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double- or multi-layered tablets, etc. 
         [0379]    To form pills, any of various known carriers can be used, including, for example, glucose, lactose, starch, cacao butter, hydrogenated vegetable oils, kaolin, talc and other excipients; gum arabic powder, tragacanth powder, gelatin, ethanol and other binders; laminaran, agar and other disintegrants; etc. 
         [0380]    To form suppositories, any of various known carriers can be used, including, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semisynthetic glycerides, etc. 
         [0381]    To form an injection, a solution, emulsion or suspension is sterilized and preferably made isotonic with blood. Any of various known widely used diluents can be employed to prepare the solution, emulsion or suspension. Examples of such diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, aliphatic acid esters of polyoxyethylene sorbitan, etc. In this case, the pharmaceutical preparation may contain sodium chloride, glucose or glycerin in an amount sufficient to prepare an isotonic solution, and may contain general solubilizers, buffers, analgesic agents, etc., and further, if necessary, coloring agents, preservatives, flavors, sweetening agents, etc., and/or other medicines. 
         [0382]    The proportion of the compound of the present invention in the pharmaceutical preparation is not limited and can be suitably selected from a wide range. It is typically preferable that the pharmaceutical preparation contain the compound of the present invention in a proportion of 1 to 70 wt. %. 
         [0383]    The route of administration of the pharmaceutical preparation according to the present invention is not limited, and the preparation can be administered by a route suitable for the form of the preparation, the patient&#39;s age and sex, the conditions of the disease, and other conditions. 
         [0384]    For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. Injections are intravenously administered singly or as mixed with general injection transfusions such as glucose solutions, amino acid solutions or the like, or singly administered intramuscularly, intracutaneously, subcutaneously or intraperitoneally, as required. Suppositories are administered intrarectally. 
         [0385]    The dosage of the pharmaceutical preparation is suitably selected according to the method of use, the patient&#39;s age and sex, the severity of the disease, and other conditions, and is typically about 0.001 to about 100 mg/kg body weight/day, and preferably 0.001 to 50 mg/kg body weight/day, in single or divided doses. 
         [0386]    Since the dosage varies depending on various conditions, a dosage smaller than the above range may be sufficient, or a dosage larger than the above range may be required. 
         [0387]    When administered to the human body as a pharmaceutical, the compound of the present invention may be used concurrently with, or before or after, antithrombotics such as blood clotting inhibitors and antiplatelet agents (e.g., warfarin, aspirin, etc.). Further, the present compound may be used concurrently with, or before or after, drugs for treating chronic diseases, such as antihypertensive drugs (ACE inhibitors, beta blockers, angiotensin II receptor antagonists), heart failure drugs (cardiotonic agents, diuretics), and diabetes treatment agents. 
         [0388]    The compound of the present invention has potent blocking effects on human Kv1.5 and/or GIRK1/4 channels, and weak blocking effects on HERG channels. Thus, the compound of the invention has characteristics as an atrial-selective K +  channel-blocking agent. 
         [0389]    Therefore, the compound of the invention can be used as a pharmacologically active substance that is safer and provides a more potent effect on the prolongation of the atrial refractory period than conventional antiarrhythmic agents. The compound of the invention is preferably used as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (elimination of arrhythmia and/or prevention of the occurrence of arrhythmia). The compound of the invention is particularly preferably used as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). The compound of the invention can also be used as a prophylactic agent for thromboembolism such as cerebral infarction and as a therapeutic agent for heart failure. 
         [0390]    The compound having potent blocking effects on both human Kv1.5 and human GIRK1/4 channels has more potent atrial refractory period prolongation effects and is highly safe, compared to compounds inhibiting either one of the channels. Furthermore, this compound has greater therapeutic effects on atrial fibrillation (defibrillation and maintenance of sinus rhythm) than compounds inhibiting either one of the channels. Therefore, the compound having potent blocking effects on both the human Kv1.5 and human GIRK1/4 channels is particularly useful as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (termination of arrhythmia and/or prevention of the occurrence of arrhythmia). This compound is particularly useful as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). 
       2. Second Invention (Amino Compound) 
       [0391]    The present inventors conducted extensive research to develop a compound that blocks the I Kur  current (Kv1.5 channel) and/or the I KA C h  current (GIRK1/4 channel) potently and more selectively than other K +  channels. As a result, the inventors found that a novel amino compound represented by General Formula (1) below could be the desired compound. The present invention has been accomplished based on the above findings. 
         [0392]    The present invention provides amino compounds, and pharmaceutical compositions comprising the amino compounds as summarized in items 1 to 7 below. 
         [0393]    Item 1. An amino compound represented by General Formula (1): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a salt thereof,
 
wherein R 1  and R 2  are each independently hydrogen or organic group;
 
X A  and X B  are each independently a bond, alkylene, alkenylene, —CO—, —SO 2 —, or —CONH—, wherein each of the alkylene and alkenylene chains can optionally contain one or more substituents selected from the group consisting of —S—, —C(═S)—SO 2 —, —CO—, —O—, —NH—, —CONH— and —SO 2 NH—, and the hydrogen atom (H) bonded to the nitrogen atom (N) in X A  and X B  is optionally substituted with a substituent selected from the group consisting of lower alkyl, phenyl lower alkyl and phenyl;
 
A 1  is lower alkylene optionally substituted with one or more substituents selected from the group consisting of hydroxyl and oxo;
 
R 3  is (i) a heterocyclic group which is optionally substituted with one or more substituents, or
 
(ii) an aryl group substituted with one or more substituents selected from the group consisting of oxo, lower alkyl, carboxyl, halo-lower alkyl, lower alkanoyl lower alkyl, phenyl lower alkyl, cyclo lower alkyl, lower alkoxy, halo lower alkoxy, phenyl lower alkoxy, phenoxy, cyano, hydroxyl, halogen, nitro, lower alkyl thio, lower alkanoyl, lower alkoxy carbonyl, lower alkenyl, phenyl, triazolyl, isoxazolyl, imidazolyl, pyrrolyl, benzo[d]oxazolyl, benzo[d]thiazolyl and the group represented by General Formula (2):
 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein Y is a bond, lower alkylene, or —CO—; R 4  and R 5  are each independently hydrogen, lower alkyl, cyclo lower alkyl, phenyl, or lower alkanoyl; or R 4  and R 5  may be linked to form a ring together with the neighboring nitrogen, and the ring may optionally have one or more substituents. 
         [0394]    Item 2. A pharmaceutical composition comprising an amino compound represented by Formula (1) or a salt thereof according to Item 1, and a pharmacologically acceptable carrier. 
         [0395]    Item 3. A pharmaceutical composition according to Item 1 for preventing and/or treating arrhythmia. 
         [0396]    Item 4. An amino compound represented by Formula (1) or a salt thereof according to Item 1 for use in the pharmaceutical composition. 
         [0397]    Item 5. Use of an amino compound represented by Formula (1) or a salt thereof according to Item 1 as a pharmaceutical composition. 
         [0398]    Item 6. Use of an amino compound represented by Formula (1) or a salt thereof according to Item 1 for the production of a pharmaceutical composition. 
         [0399]    Item 7. A method of preventing and/or treating arrhythmia, comprising administering to a patient an amino compound represented by Formula (1) or a salt thereof according to Item 1. 
         [0400]    The groups represented by, or substituents of, R 1 , R 2 , R 3 , R 4 , R 5 , A 1 , X A , X B  and Y in the specification are described below. 
         [0401]    The term “one or more” may be preferably 1 to 6, more preferably 1 to 3. 
         [0402]    Examples of “lower alkyl” include linear or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, n-hexyl, isohexyl, and 3-methylpentyl. 
         [0403]    Examples of “alkylene” include linear or branched alkylene groups having 1 to 12 carbon atoms, such as the following “lower alkylene”, heptamethylene, octamethylene, decamethylene, and dodecamethylene. 
         [0404]    Examples of “lower alkylene” include linear or branched alkylene groups having 1 to 6 carbon atoms, such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, dimethylmethylene, tetramethylene, pentamethylene, and hexamethylene. 
         [0405]    Examples of “alkenylene” include linear or branched alkylene groups having 2 to 12 carbon atoms, such as the following “lower alkenylene”, heptenylene, octenylene, decenylene, and dodecenylene. 
         [0406]    Examples of “lower alkenylene” include linear or branched alkylene groups having 2 to 6 carbon atoms, such as ethenylene, propenylene, butenylene, pentenylene, and hexenylene. 
         [0407]    Examples of “lower alkylidene” include linear or branched alkylidene groups having 1 to 6 carbon atoms, such as methylidene, ethylidene, propylidene, and butylidene. 
         [0408]    Examples of “cyclo lower alkyl” include linear or branched cyclo alkyl having 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. 
         [0409]    Examples of “lower alkoxy” include linear or branched alkoxy groups having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy, and 3-methylpentyloxy. 
         [0410]    Examples of “halogen” include fluorine, chlorine, bromine, and iodine. 
         [0411]    Examples of “lower alkylenedioxy” include linear or branched alkylene groups having 1 to 4 carbon atoms, such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy. 
         [0412]    Examples of “lower alkanoyl” include linear or branched alkanoyl groups having 1 to 6 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl. 
         [0413]    Examples of “lower alkoxycarbonyl” include (linear or branched alkoxy having 1 to 6 carbon atoms)carbonyls, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and tert-butoxycarbonyl. 
         [0414]    Examples of “aralkyl group” include lower alkyl group substituted with one or more aryl groups, such as benzyl and phenethyl. 
         [0415]    Examples of “organic group” include lower alkyl, lower alkoxy, cyclo lower alkyl, amino, lower alkyl thio, aryl, and heterocyclic group, each of which is optionally substituted. 
         [0416]    Examples of “aryl group” include monocyclic or polycyclic aryl groups, such as phenyl, tolyl, xylyl, naphthyl and tetrahydronaphthyl, indenyl, and dihydroindenyl. 
         [0417]    Examples of “heterocyclic group” include saturated or unsaturated monocyclic or polycyclic heterocyclic groups containing at least one hetero atom selected from the group consisting of oxygen, sulfur and nitrogen. More preferable examples of heterocyclic groups include the following (a) to (o): 
         [0418]    (a) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, and its N-oxide, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), dihydrotriazinyl (e.g., 4,5-dihydro-1,2,4-triazinyl, 2,5-dihydro-1,2,4-triazinyl, etc.), etc.; 
         [0419]    (b) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, pyrazolidinyl, piperazinyl, 1,4-diazepanyl, etc.; 
         [0420]    (c) saturated or unsaturated condensed 7- to 14-membered heterocyclic groups containing 1 to 5 nitrogen atom(s), for example, decahydroquinolyl, indolyl, dihydroindolyl (e.g., 2,3-dihydroindolyl, etc.), isoindolyl, indolizinyl, benzimidazolyl, d′ hydrobenzimidazolyl (e.g., 2,3-dihydro-1H-benzo[d]imidazolyl, etc.), quinolyl, dihydroquinolyl (e.g. 1,4-dihydroquinolyl, 1,2-dihydroquinolyl, etc.), tetrahydroquinolyl (1,2,3,4-tetrahydroquinolyl, etc.), isoquinolyl, dihydroisoquinolyl (e.g., 3,4-dihydro-1H-isoquinolyl, 1,2-dihydroisoquinolyl, etc.), tetrahydroisoquinolyl (e.g., 1,2,3,4-tetrahydro-1H-isoquinolyl, 5,6,7,8-tetrahydroisoquinolyl, etc.), carbostyril, dihydrocarbostyril (e.g., 3,4-dihydrocarbostyril, etc.), indazolyl, benzotriazolyl (e.g. benzo[d][1,2,3]triazolyl, etc.), tetrazolopyridyl, tetrazolopyridazinyl (e.g., tetrazolo[1,5-b]pyridazinyl, etc.), dihydrotriazolopyridazinyl, imidazopyridyl (e.g., imidazo[1,2-a]pyridyl, imidazo[4,5-c]pyridyl, etc.), naphthyridinyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolopyridyl (e.g., pyrazolo[2,3-a]pyridyl, etc.) tetrahydropyridoindolyl (e.g., 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, etc.), etc.; 
         [0421]    (d) saturated or unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s), for example, furyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl, etc.), tetrahydrofuryl, etc.; 
         [0422]    (e) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 3 oxygen atom(s), for example, benzofuryl, dihydrobenzofuryl (e.g. 2,3-dihydrobenzo[b]furyl, etc.), chromanyl, benzodioxanyl (e.g., 1,4-benzodioxanyl, etc.), benzodioxolyl (benzo[1,3]dioxolyl, etc.), etc.; 
         [0423]    (f) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.), etc.; 
         [0424]    (g) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, etc.; 
         [0425]    (h) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, benzisoxazolyl, dihydrobenzoxazinyl (e.g., 2,3-dihydrobenz-1,4-oxazinyl, etc.), furopyridyl (e.g., furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, etc.), furopyrrolyl (e.g., furo[3,2-b]pyrrolyl etc.) etc.; 
         [0426]    (i) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl, 1,2-thiazolyl, thiazolinyl, thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,2,3-thiadiazolyl, etc.), isothiazolyl, etc.; 
         [0427]    (j) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, etc.; 
         [0428]    (k) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing a sulfur atom, for example, thienyl, etc.; 
         [0429]    (l) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 3 sulfur atom(s), for example, benzothienyl (e.g. benzo[b]thienyl), etc.; 
         [0430]    (m) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzo[d]isothiazolyl, 2,3-dihydro benzo[d]isothiazolyl, benzothiadiazolyl, thienopyridyl (e.g., thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, thieno[3,2-c]pyridyl, 4,5-dihydrothieno[3,2-c]pyridyl, thieno[2,3-b]pyridyl, 6,7-dihydrothieno[2,3-b]pyridyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridyl, etc.), imidazothiazolyl (e.g., imidazo[2,1-b]thiazolyl, etc.), dihydroimidazothiazolyl (e.g., 2,3-dihydroimidazo[2,1-b]thiazolyl, etc.), thienopyrazinyl (e.g., thieno[2,3-b]pyrazinyl, etc.), etc.; 
         [0431]    (n) saturated or unsaturated 7- to 12-membered heterocyclic spiro groups containing 1 to 2 nitrogen atom(s), for example, azaspiroundecanyl (e.g., 3-azaspiro[5.5]undecanyl), etc.; and 
         [0432]    (o) saturated 7- to 12-membered hetero bicyclic groups containing 1 to 3 nitrogen atom(s), for example, azabicyclooctanyl (e.g., (1R,5S)-8-azabicyclo[3.2.1]octanyl), etc; 
         [0433]    wherein said heterocyclic group may be substituted by one or more suitable substituents. 
         [0434]    Substituents of “aryl group which is optionally substituted” represented by R 1  and R 2  are each independently one or more substituents selected from the group consisting of: 
         [0000]    (a1) cyano;
 
(a2) hydroxyl;
 
(a3) halogen;
 
(a4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, hydroxyl, imidazolyl, morpholinyl, triazolyl and phenyl;
 
(a5) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of halogen, amino, lower alkyl amino and phenyl;
 
(a6) pyridyl;
 
(a7) thienyl;
 
(a8) piperazinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and halo phenyl lower alkyl;
 
(a9) phenyl;
 
(a10) pyrazolyl optionally substituted with one or more lower alkyl;
 
(a11) pyrimidinyl optionally substituted with one or more lower alkyls;
 
(a12) piperidyl optionally substituted with one or more lower alkyls;
 
(a13) furyl;
 
(a14) carboxy;
 
(a15) lower alkoxycarbonyl;
 
(a16) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, phenyl, lower alkanoyl and lower alkylsulfonyl;
 
(a17) lower alkylthio;
 
(a18) triazolyl;
 
(a19) imidazolyl;
 
(a20) pyrrolidinyl optionally substituted with one or more oxos;
 
(a21) lower alkylsulfonyl;
 
(a22) lower alkylenedioxy optionally substituted with one or more halogens;
 
(a23) nitro;
 
(a24) oxazolyl;
 
(a25) thiazolyl optionally substituted with one or more lower alkyls;
 
(a26) lower alkanoyl;
 
(a27) sulfo;
 
(a28) carbamoyl optionally substituted with one or two lower alkyls;
 
(a29) phenoxy;
 
(a30) isoxazolyl;
 
(a31) pyrrolyl;
 
(a32) lower alkenyl;
 
(a33) cyclo lower alkyl;
 
(a34) benzo[d]oxazolyl; and
 
(a35) oxo.
 
         [0435]    Substituents of “heterocyclic group which is optionally substituted” represented by R 1  and R 2  are each independently one or more substituents selected from the group consisting of: 
         [0000]    (h1) oxo;
 
(h2) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, phenyl amino, cyclo lower alkyl, lower alkoxy, pyridyl, mono- or di-lower alkyl amino, hydroxyl, lower alkyl substituted isoxazolyl, 1,3-dioxolanyl, lower alkyl substituted piperidinyl, mono or di lower alkyl amino, fulyl, imidazolyl, morpholinyl, lower alkyl substituted 1,4-diazepanyl, phenyl thiazolyl, phenyl lower alkyl tetrazolyl, lower alkyl tetrazolyl, quinolyl, pyrrolyl, imidazolyl, 2,3-dihydrobenzofuryl and benzodioxolyl;
 
(h3) cyclo lower alkyl;
 
(h4) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of pyridyl, halo-lower alkoxy pheny, halo phenyl, phenyl, and halo-lower alkyl phenyl;
 
(h5) aryl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, halo-lower alkyl, lower alkoxy, halo lower alkoxy, lower alkanoyl, hydroxyl, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkyl amino, and cyano;
 
(h6) aralkyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, halo-lower alkyl, lower alkoxy, halo-lower alkoxy, lower alkanoyl, hydroxyl, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkyl amino, cyano, phenyl, and oxo, on the aryl and/or lower alkyl group of aralkyl;
 
(h7) heterocyclic group optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkanoyl, hydroxyl, halogen, carboxy, lower alkoxycarbonyl, amino, lower alkyl amino, cyano, phenyl, and oxo;
 
(h8) hydroxyl;
 
(h9) halogen;
 
(h10) carboxy;
 
(h11) lower alkanoyl;
 
(h12) lower alkoxycarbonyl;
 
(h13) lower alkylenedioxy;
 
(h14) cyano;
 
(h15) nitro;
 
(h16) sulfo;
 
(h17) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, mono- or di-lower alkyl amino lower alkyl, (lower alkyl) (phenyl)amino lower alkyl, lower alkyl substituted phenoxy lower alkyl, phenyl lower alkyl, cyclo lower alkyl lower alkyl, lower alkyoxy phenyl lower alkyl, lower alkyl phenyl lower alkyl, triazolyl lower alkyl, halo substituted phenyl, halo-lower alkyl substituted phenyl, halo-lower alkoxy substituted phenyl, piperazinyl lower alkyl carbonyl, phenyl lower alkyl carbonyl and lower alkoxy dihydroindenyl;
 
(h18) lower alkylthio;
 
(h19) lower alkylsulfonyl;
 
(h20) lower alkenyl optionally substituted with one or more phenyls;
 
(h21) benzo[d][1,3]dioxolyl carbonyl;
 
(h22) 2,3-dihydroindenyl;
 
(h23) phenoxy substituted with one or more substituents selected from the group consisting of halo-lower alkoxy and halogen;
 
(h24) lower alkylidene substituted with one or more lower alkoxy phenyls;
 
         [0436]    Substituents of “lower alkyl group which is optionally substituted” represented by R 1  and R 2  are each independently one or more substituents selected from the group consisting of oxo and phenyl. 
         [0437]    Substituents of “cyclo lower alkyl group which is optionally substituted” represented by R 1  and R 2  are each independently one or more substituents selected from the group consisting of lower alkyl phenyl and phenyl. 
         [0438]    Substituents of “amino group which is optionally substituted” represented by R 1  and R 2  are each independently one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and phenyl lower alkyl. 
         [0439]    Substituents of “dihydroindenyl group which is optionally substituted” represented by R 1  and R 2  are each independently one or more oxos. 
         [0440]    Preferable substituents represented by R 1  and R 2  are each independently selected from the group consisting of the following substituents (1) to (69): 
         [0000]    (1) hydrogen;
 
(2) lower alkyl optionally substituted with one or more substituents selected from the group consisting of oxo and phenyl;
 
(3) cyclo lower alkyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl phenyl and phenyl;
 
(4) phenyl optionally substituted with one or more substituents selected from the group consisting of the following (4-1) to (4-25):
       (4-1) cyano;   (4-2) hydroxyl;   (4-3) halogen;   (4-4) lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, imidazolyl, hydroxyl, triazolyl (e.g, 1,2,4-triazolyl) and morpholinyl;   (4-5) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of amino and lower alkyl amino;   (4-6) pyridyl;   (4-7) thienyl;   (4-8) piperazinyl optionally substituted with one or more lower alkyls;   (4-9) phenyl;   (4-10) pyrazolyl optionally substituted with one or more lower alkyls;   (4-11) pyrimidinyl optionally substituted with one or more lower alkyls;   (4-12) piperidyl optionally substituted with one or more lower alkyls;   (4-13) furyl;   (4-14) carboxy;   (4-15) lower alkoxycarbonyl;   (4-16) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and lower alkylsulfonyl;   (4-17) lower alkylthio;   (4-18) triazolyl;   (4-19) imidazolyl;   (4-20) pyrrolidinyl optionally substituted with one or more oxos;   (4-21) lower alkylsulfonyl;   (4-22) lower alkylenedioxy optionally substituted with one or more halogens;   (4-23) nitro;   (4-24) oxazolyl;   (4-25) thiazolyl optionally substituted with one or more lower alkyls;   (4-26) phenoxy; and   (4-27) carbamoyl optionally substituted with one or two lower alkyls;
 
(5) naphthyl;
 
(6) furyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen, carboxy, sulfo, pyridyloxy, lower alkoxycarbonyl, and phenyl;
 
(7) thienyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkylenedioxy, carboxy, halogen, pyridyl, lower alkoxy, lower alkoxycarbonyl, oxazolyl, and furyl;
 
(8) imidazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl, and halogen;
 
(9) pyrazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen, halogen, phenyl optionally substituted with lower alkoxy, furyl, and thienyl;
 
(10) oxazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(11) isoxazolyl optionally substituted with one or more substituents selected from the group consisting of phenyl, lower alkyl, thienyl, and furyl;
 
(12) thiazolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with lower alkoxy, phenyl, and lower alkanoylamino;
 
(13) pyrrolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and lower alkoxycarbonyl;
 
(14) triazolyl optionally substituted with one or more lower alkyls;
 
(15) pyridyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl optionally substituted with halogen, oxo, hydroxyl, lower alkoxy, halogen, pyrrolidinyl, morpholinyl, thienyl, piperazinyl lower alkyl carbonyl amino;
 
(16) pyrimidinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and phenyl;
 
(17) pyridazinyl;
 
(18) pyrazinyl;
 
(19) imidazo[2,1-b]thiazolyl optionally substituted with one or more halogens;
 
(20) thieno[2,3-b]pyrazinyl;
 
(21) 2,3-dihydroimidazo[2,1-b]thiazolyl optionally substituted with one or more phenyls;
 
(22) benzothiazolyl optionally substituted with one or more lower alkyls;
 
(23) indolyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and halogen;
 
(24) imidazo[1,2-a]pyridyl optionally substituted with one or more lower alkyls;
 
(25) benzothienyl optionally substituted with one or more lower alkyls;
 
(26) benzimidazolyl optionally substituted with one or more lower alkyls;
 
(27) 2,3-dihydrobenzo[b]furyl;
 
(28) benzofuryl optionally substituted with one or more halogens;
 
(29) indazolyl optionally substituted with one or more lower alkyls;
 
(30) furo[2,3-c]pyridyl or 6,7-dihydrofuro[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(31) furo[3,2-c]pyridyl or 4,5-dihydrofuro[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl optionally substituted with halogen, halogen, furyl, pyridyl, and phenyl optionally substituted with one or more substituents selected from the group consisting of amino and lower alkoxy;
 
(32) thieno[2,3-c]pyridyl or 6,7-dihydrothieno[2,3-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo group and lower alkyl;
 
(33) thieno[3,2-c]pyridyl or 4,5-dihydrothieno[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(34) thieno[2,3-b]pyridyl;
 
(35) benzo[1,3]dioxolyl optionally substituted with one or more halogens;
 
(36) benzisoxazolyl;
 
(37) pyrazolo[2,3-a]pyridyl;
 
(38) indolizinyl;
 
(39) 2,3-dihydroindolyl optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkyl, and lower alkanoyl;
 
(40) isoquinolyl or 1,2-dihydroisoquinolyl, each of which is optionally substituted with one or more substituents selected from the group consisting of lower alkyl, halogen, lower alkoxy and oxo;
 
(41) 1,2,3,4-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(42) 1,2-dihydroquinolyl optionally substituted with one or more substituents selected from the group consisting of lower alkoxy and oxo;
 
(43) 1,2,3,4-tetrahydroquinolyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkoxy;
 
(44) quinolyl optionally substituted with one or more substituents selected from the group consisting of amino optionally substituted with one or two lower alkyl, lower alkoxy, lower alkyl, and oxo;
 
(45) chromanyl optionally substituted with one or more lower alkyls;
 
(46) 5,6,7,8-tetrahydroisoquinolyl optionally substituted with one or more oxos;
 
(47) 3,4-dihydroisoquinolyl optionally substituted with one or more oxos;
 
(48) naphthyridinyl;
 
(49) 1,4-benzodioxanyl;
 
(50) cinnolinyl;
 
(51) quinoxalinyl;
 
(52) 2,3-dihydrobenz-1,4-oxazinyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and oxo;
 
(53) 2,3-dihydroindenyl optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkoxy;
 
(54) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl and phenyl lower alkyl;
 
(55) lower alkoxy;
 
(56) lower alkylthio;
 
(57) decahydroquinolyl;
 
(58) piperazinyl optionally substituted with one or more substituents selected from the group consisting of
   (58-1) lower alkyl optionally substituted with one or more substituents selected from the group consisting of oxo, lower alkoxy, 1,3-dioxolanyl, lower alkyl-substituted piperidyl, furyl, imidazolyl, phenyl amino, phenyl-substituted thiazolyl, phenyl lower alkyl-substituted tetrazolyl, lower alkyl-substituted tetrazolyl, quinolyl, pyrrolyl, mono- or di-lower alkyl amino, pyridyl and benzo[d][1,3]dioxolyl;   (58-2) oxo;   (58-3) halo-lower alkyl substituted phenyl amino;   (58-4) cyclo lower alkyl;   (58-5) 2,3-dihydroindenyl;   (58-6) phenyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, halo-lower alkyl and halo-lower alkoxy; and   (58-7) phenyl lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, halo-lower alkyl, halo-lower alkoxy and pyridyl, on the benzene ring and/or lower alkyl of phenyl lower alkyl;
 
(59) 1,4-diazepanyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl, pyridyl and morpholinyl lower alkyl;
 
(60) piperidyl optionally substituted with one or more substituents selected from the group consisting of:
   (60-1) lower alkyl optionally substituted with one or more substituents selected from the group consisting of oxo, mono- or di-lower alkylamino, 2,3-dihydrobenzofuryl and imidazolyl;   (60-2) amino optionally substituted with one or two substituents selected from the group consisting of lower alkyl, halo-phenyl, halo-lower alkoxy-substituted phenyl, mono- or di-lower alkyl amino lower alkyl, lower alkyl-substituted phenoxy lower alkyl, phenyl lower alkyl, phenyl lower alkyl carbonyl, cyclo lower alkyl lower alkyl, lower alkoxy phenyl lower alkyl, 1,2,4-triazolyl lower alkyl, pyridyl phenyl, (phenyl) (lower alkyl)amino lower alkyl, lower alkoxy-substituted 2,3-dihydro-1H-indenyl and lower alkyl phenyl lower alkyl;   (60-3) lower alkoxy optionally substituted with one or more substituents selected from the group consisting of phenyl, halo-phenyl, halo-lower alkoxy-substituted phenyl, halo-lower alkyl substituted phenyl and pyridyl;   (60-4) phenoxy optionally substituted with one or more substituents selected from the group consisting of halogen, and halo-lower alkoxy;   (60-5) phenyl lower alkyl optionally substituted with one or more substituents selected from the group consisting of halogen, oxo, lower alkoxy and amino, on the benzene ring and/or lower alkyl of phenyl lower alkyl;   (60-6) lower alkoxy phenyl lower&#39;alkylidene;   (60-7) phenyl imidazolyl;   (60-8) phenyl morpholinyl; and   (60-9) phenyl;
 
(61) morpholinyl optionally substituted with one or more mono- or di-lower alkyl amino-substituted piperidyl lower alkyls;
 
(62) benzo[d][1,2,3]triazolyl optionally substituted with one or more lower alkyls;
 
(63) 4,5,6,7-tetrahydrothieno[2,3-c]pyridyl;
 
(64) 2,3,4,9-tetrahydropyrido[3,4-b]indolyl);
 
(65) 3-azaspiro[5,5]undecanyl;
 
(66) 8-azabicyclo[3,2,1]octanyl;
 
(67) tetrahydro-2H-pyranyl;
 
(68) furo[3,2-b]pyrrolyl optionally substituted with one or more lower alkyls; and
 
(69) tetrahydrofuryl.
       
 
         [0484]    Preferable examples of “aryl group which is optionally substituted” for R 1  and R 2  include the substituents (4), (5) and (53). 
         [0485]    Preferable examples of “heterocyclic group which is optionally substituted” for R 1  and R 2  include the substituents (6) to (52) and (57) to (69). 
         [0486]    Examples of X A  and X B  include a bond, lower alkylene, lower alkenylene, —CO—, —SO 2 —, -lower alkylene-SO 2 —, -lower alkylene-CO—, -lower alkenylene-CO—, -lower alkylene-CO—N(lower alkyl)-lower alkylene-, —N(lower alkyl)-lower alkylene-, —CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-, —N(phenyl lower alkyl)-lower alkylene-, —CO-lower alkylene-CO—, —CO—NH-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-, -lower alkylene-N(lower alkyl)-lower alkylene-O—, -lower alkylene-NH-lower alkylene-, -lower alkylene-SO 2 —NH-lower alkylene-, —N(lower alkyl)-CO-lower alkylene-, —N(lower alkyl)-lower alkylene-CO—, —N(lower alkyl)-lower alkylene-N(lower alkyl)-lower alkylene-, —N(phenyl)-lower alkylene-CO—, —NH—CO—, —NH—CO-lower alkylene-, —NH-lower alkylene-, —O-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —O-lower alkylene-CO—, —NH-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —S-lower alkylene-CO—N(lower alkyl)-lower alkylene-, —SO 2 —N(lower alkyl)-lower alkylene-, —SO 2 —NH-lower alkylene-, -lower alkenylene-CO—N(lower alkyl)-lower alkylene-, —N(phenyl)-lower alkylene-CO—N(lower alkyl)-lower alkylene-, and —CO-lower alkylene-O—CO—. 
         [0487]    Either of the two bonds in X A  may be bonded to R 1  or N, and either of the two bonds in X B  may be bonded to R 2  or N. 
         [0488]    Examples of “lower alkylene optionally substituted with one or more substituents selected from the group consisting of hydroxyl and oxo” represented by A 1  are C 1-6  alkylene and —CO—C 1-6  alkylene-. 
         [0489]    Examples of heterocyclic groups of “heterocyclic group which is optionally substituted” represented by R 3  include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinolyl, 1,2-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, isoquinolyl, 1,2-dihydroisoquinolyl, 1,2,3,4-tetrahydroisoquinolyl, quinazolinyl, 1,2,3,4-tetrahydroquinazolinyl, quinoxalinyl, 1,2,3,4-tetrahydroquinoxalinyl, indolyl, 2,3-dihydroindolyl, isoindolyl, 1,3-dihydroisoindolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, benzo[d]isothiazolyl, 2,3-dihydrobenzo[d]isothiazolyl, 2,3,4,5-tetrahydrobenz[f]1,4-thiazepinyl, 1,7-naphthyridinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, benzo[d][1,3]dioxolyl, benzo[d]thiazolyl, benzo[d][1,3]oxathiolyl, 2H-chromenyl, 2H-pyranyl, benzofuryl, 3,4-dihydro-2H-benzo[b][1,4]thiazinyl, 2,3,4,5-tetrahydrobenzo[e][1,4]diazepinyl, 2,3,4,5-tetrahydrobenzo[b]azepinyl, 2,3-dihydrobenzo[d]thiazolyl, 2,3-dihydrobenzo[d]oxazolyl, 2,3,4,5-tetrahydrobenzo[c]azepinyl, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepinyl, benzo[d]oxazolyl, benzo[d]isoxazolyl, benzo[c][1,2,5]oxadiazolyl, 2H-pyranyl, 3,4-dihydroisoquinolyl, 2,3,4,5-tetrahydrobenzo[f][1,4]oxazepinyl, 1,2,3,5-tetrahydrobenzo[e][1,4]oxazepinyl, 2,3,4,5-tetrahydrobenzo[b][1,4]oxazepinyl, dibenzo[b,d]furyl, 9H-carbazolyl, benzo[c][1,2,5]oxadiazolyl, 1,2,3,4,5,6-hexahydrobenzo[b]azocinyl, 2,3-dihydrobenzofuryl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, 2,4-dihydro-1H-benzo[d][1,3]oxazinyl, and benzo[b]thiophenyl. 
         [0490]    Examples of substituents of “substituted heterocyclic group” represented by R 3  include the substituents (h1) to (h17) and (h20) to (h24), which are mentioned as substituents of heterocyclic groups represented by R 1  and R 2 . Among these, preferable substituents are (h1), (h2), (h5), (h6), (h8), (h10), (h11), (h12) and (h20), and more preferable substituents are (h1) and/or (h2). 
         [0491]    Examples of aryl groups of “ary group which is substituted” represented by R 3  include those as defined above. 
         [0492]    When R 4  and R 5  in General Formula (2) are linked to form a ring together with the neighboring nitrogen, examples of the group —NR 4 R 5  include the following: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0493]    Each of the ring may optionally have one or more substituents selected from the group consisting of oxo; lower alkyl; phenyl lower alkyl; halo-phenyl lower alkyl; and amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, phenyl and halo-phenyl. 
         [0494]    The amino compound of the present invention represented by General Formula (1) or its salt can be readily produced by persons skilled in the art using technical knowledge, based on the Examples and Reference Examples of the present specification. For example, the amino compound or its salt can be produced according to the processes shown in the following reaction formulae. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , X A , X B  and A 1  are the same as above; and X 1  is a leaving group. 
         [0495]    The reaction of the compound of Formula (3) with the compound of Formula (4) can be performed in a general inert solvent or without using any solvent, in the presence or absence of a basic compound. 
         [0496]    Examples of the leaving groups represented by X 1  include halogen atoms (e.g., chlorine, bromine, iodine, and like atoms), lower alkane sulfonyloxy (e.g., methanesulfonyloxy), halo substituted lower alkane sulfonyloxy (e.g., trifluoromethanesulfonyloxy), arylene sulfonyloxy (e.g., p-toluenesulfonyloxy, benzenesulfonyloxy), etc. 
         [0497]    Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethylether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower (C 1-5 ) alcohols such as methanol, ethanol, and isopropanol; ketones such as acetone and methyl ethyl ketone; polar solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide, and acetonitrile; and mixtures thereof. 
         [0498]    A wide variety of known basic compounds can be used as the basic compound. Examples of usable basic compounds include inorganic bases, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, lithium hydrogencarbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; alkali metals such as sodium and potassium; sodium amide; sodium hydride; and potassium hydride; and organic bases, for example, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, and potassium ethoxide; triethylamine, tripropylamine, pyridine, quinoline, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds can be used singly or in a combination of two or more. 
         [0499]    The above reaction may be performed by adding as a reaction accelerator an alkali metal iodide such as potassium iodide or sodium iodide to the reaction system, as required. 
         [0500]    The compound of Formula (4) is typically used in an amount of at least 0.5 moles, and preferably about 0.5 to about 10 moles, per mole of the compound of Formula (3). 
         [0501]    The amount of basic compound is typically 0.5 to 10 moles, and preferably 0.5 to 6 moles, per mole of the compound of Formula (3). 
         [0502]    The reaction is typically performed at a temperature of 0 to 250° C., and preferably 0 to 200° C., and is typically completed in about 1 to about 80 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , X A  and A 1  are the same as above; and R 2a  is hydrogen or lower alkyl. 
         [0503]    Examples of lower alkyl groups represented by R 2a  include linear or branched alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, and isopropyl. 
         [0504]    The reaction between the compound of Formula (1b) and the compound of Formula (5) is performed, for example, in an inert solvent or suitable solvent, in the presence of a reducing agent. Examples of usable solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, isopropanol, butanol, tert-butanol, and ethylene glycol; aliphatic acids such as acetonitrile, formic acid, and acetic acid; ethers such as diethylether, tetrahydrofuran, dioxane, monoglyme, and diglyme; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; and mixtures thereof. 
         [0505]    Examples of reducing agents include aliphatic acids such as formic acid; aliphatic acid alkali metal salts such as sodium formate; hydride reducing agents such as sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, sodium trimethoxyborohydride, and lithium aluminium hydride; and mixtures thereof, or mixtures of aliphatic acids or aliphatic acid alkali metal salts and hydride reducing agents; and catalytic hydrogenation reducing agents such as palladium black, palladium carbon, platinum oxide, platinum black, and Raney nickel. 
         [0506]    When an aliphatic acid such as formic acid, or an aliphatic acid alkali metal salt such as sodium formate is used as a reducing agent, a suitable reaction temperature is typically about room temperature to about 200° C., and preferably about 50 to about 150° C. The reaction is typically completed in about 10 minutes to about 10 hours. Preferably, the aliphatic acid or aliphatic acid alkali metal salt is used in large excess relative to the compound of Formula (1b). 
         [0507]    When a hydride reducing agent is used, a suitable reaction temperature is typically about −80 to about 100° C., and preferably about −80 to about 70° C. The reaction is typically completed in about 30 minutes to about 60 hours. The hydride reducing agent is typically used in an amount of about 1 to about 20 moles, and preferably about 1 to about 10 moles, per mole of the compound of Formula (1b). Particularly when lithium aluminium hydride is used as a hydride reducing agent, it is preferable to use as a solvent an ether such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, and diglyme; or an aromatic hydrocarbon such as benzene, toluene, or xylene. To the reaction system of the reaction may be added an amine such as trimethylamine, triethylamine, or N-ethyldiisopropylamine; or a molecular sieve such as molecular sieve 3A (MS-3A) or molecular sieve 4A (MS-4A). 
         [0508]    When a catalytic hydrogenation reducing agent is used, the reaction is typically performed at about −30 to about 100° C., and preferably about 0 to about 60° C., in a hydrogen atmosphere at typically about atmospheric pressure to about 20 atm, and preferably at about atmospheric pressure to about 10 atm, or in the presence of a hydrogen doner such as formic acid, ammonium formate, cyclohexene, or hydrazine hydrate. The reaction is typically completed in about 1 to about 12 hours. The catalytic hydrogenation reducing agent is typically used in an amount of about 0.1 to about 40 wt %, and preferably about 1 to about 20 wt %, based on the compound of Formula (1b). 
         [0509]    In the reaction of the compound of Formula (1b) and the compound of Formula (5), the compound of Formula (5) is typically used in an amount of at least 1 mole, and preferably 1 to 5 moles, per mole of the compound of Formula (1b). 
         [0510]    The compound of Formula (5) may also be a hydrated compound wherein a water molecule is attached to a carbonyl group. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , X A , X B , A 1  and X 1  are the same as above. 
         [0511]    The reaction of the compound of Formula (1b) with the compound of Formula (6) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (3) with the compound of Formula (4) shown in Reaction Formula 1 above. 
         [0512]    Alternatively, the reaction of the compound of Formula (1b) with the compound of Formula (6) can be performed by the known “Ullmann condensation”, “Palladium coupling reaction”, etc. The reaction can be preferably adopted especially when X B  is a bond and R 2  is aryl or heterocyclic (especially unsaturated heterocyclic) group optionally substituted. For example, the reaction can be carried out in a solvent (e.g. toluene, tetrahydrofuran (THF), N, N-dimethylformamide (DMF) N-methylpyrrolidone(NMP) and dimethyl sulfoxide(DMSO)), in the presence of transition metal compound (e.g., Pd(OAc) 2 , Pd 2 (dba) 3  and copper iodide), a basic compound (e.g., sodium tert-butoxide, K 3 PO 4  and Cs 2 CO 3 ), and if necessary a phosphine (e.g., xantphos, tri-tert-butylphosphine, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl(BINAP), tetrafluoroborate, N,N′-dimethylethylenediamine, and L-proline). 
         [0513]    The reaction temperature is not limited, and the reaction is usually carried out at ambient temperature, under warming or under heating. 
         [0514]    The compound of Formula (3), which is used as a starting material, can be easily prepared by the process shown in the following reaction formula. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 2a , X A , X B  and X 1  are the same as above. 
         [0515]    The reaction of the compound of Formula (3a) with the compound of Formula (7) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (1b) with the compound of Formula (5) shown in Reaction Formula 2 above. 
         [0516]    The reaction of the compound of Formula (3a) with the compound of Formula (6) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (3) with the compound of Formula (4) shown in Reaction Formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1- , R 2 , R 3 , X A , X B  and A 1  are the same as above. 
         [0517]    The reaction of the compound of Formula (8) with the compound of Formula (9) can be performed by the known “Mitsunobu reaction” conditions (e.g., using diethyl azodicarboxylate (DEAD) and triphenylphosphine). 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , X A , X B , X 1  and A 1  are the same as above. 
         [0518]    The reaction of the compound of Formula (10) with the compound of Formula (9) can be performed by the known O-alkylation reaction. For example, The reaction can be performed in the presence of an inert solvent (e.g., DMF, THF, dioxane and acetonitrile) and in the presence of a basic compound (e.g., K 2 CO 3  and Cs 2 CO 3 ). 
         [0519]    The reaction temperature is not limited, and the reaction is usually carried out at ambient temperature, under warming or under heating. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , X A  and X B  are the same as above; and A 10  is a divalent residue which is obtained by removing —CH 2 — from group A 1 . 
         [0520]    The reaction of the compound of Formula (3) with the compound of Formula (11) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (1b) with the compound of Formula (5) shown in Reaction Formula 2 above, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 3 , X 1 , X 2  and A 1  are the same as above. 
         [0521]    The reaction of the compound of Formula (9) with the compound of Formula (15) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (9) with the compound of Formula (10) shown in Reaction Formula 6 above. 
         [0522]    The reaction of the compound of Formula (9) with the compound of Formula (12) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (9) with the compound of Formula (10) shown in Reaction Formula 6 above. 
         [0523]    The reaction of the compound of Formula (4) with the compound of Formula (13) can be performed by the known N-alkylation reaction. For example, The reaction can be performed in the presence of an inert solvent (e.g., DMF, THF, dioxane and acetonitrile) and in the presence of a basic compound (e.g., K 2 CO 3  and Cs 2 CO 3 ). 
         [0524]    The N-alkylation reaction temperature is not limited, and the reaction is usually carried out at ambient temperature, under warming or under heating. 
         [0525]    The reaction converting the compound of Formula (14) to the compound of Formula (1e) can be performed by the known method. For example, The reaction can be performed in the presence of hydrazine. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , X A , X B , X 1  and A 1  are the same as above; and P is a hydroxyl-protecting group and X 2  is a leaving group. 
         [0526]    Examples of hydroxyl-protecting groups represented by P include tetrahydropyran-2-yl, methoxymethyl, benzyl. 
         [0527]    Examples of the leaving groups represented by X 2  include halogen atoms (e.g., chlorine, bromine, iodine, and like atoms), lower alkanesulfonyloxy (e.g., methanesulfonyloxy), halo substituted lower alkane sulfonyloxy (e.g., trifluoromethanesulfonyloxy), arylene sulfonyloxy (e.g., p-toluenesulfonyloxy, benzenesulfonyloxy), etc. 
         [0528]    When X 1  and X 2  are both halogen atoms, the halogen atom represented by X 2  is preferably one having an atomic number equal to or higher than that of the halogen atom represented by X 1 . 
         [0529]    The reaction of the compound of Formula (3) with the compound of Formula (12) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (3) with the compound of Formula (4) shown in Reaction Formula 1 above. 
         [0530]    The reaction of the compound of Formula (3) with the compound of Formula (17) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (3) with the compound of Formula (4) shown in Reaction Formula 1 above. 
         [0531]    The reaction converting the compound of Formula (18) to the compound of Formula (8) can be performed under the known deprotection method depending on the type of the protecting group (P). 
         [0532]    The compound of Formula (1) according to the present invention and the starting materials thereof can be produced using a known or conventional synthetic method other than the production method described above. 
         [0533]    In addition, compounds in the form in which a solvate (for example, a hydrate, ethanolate, etc.) was added to the starting material compounds and object compounds shown in each of the reaction formulae are included in each of the formulae. 
         [0534]    The compound of Formula (1) according to the present invention includes stereoisomers and optical isomers. 
         [0535]    The starting material compounds and object compounds represented by each of the reaction formulae can be used in an appropriate salt form. 
         [0536]    Each of the object compounds obtained according to the above reaction formulae can be isolated and purified from the reaction mixture by, for example, after cooling the reaction mixture, performing an isolation procedure such as filtration, concentration, extraction, etc., to separate a crude reaction product, and then subjecting the crude reaction product to a usual purification procedure such as column chromatography, recrystallization, etc. 
         [0537]    Among the compounds of the present invention, those having a basic group or groups can easily form salts with common pharmaceutically acceptable acids. Examples of such acids include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and other inorganic acids, methansulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malic acid, lactic acid and other organic acids, etc. 
         [0538]    Among the compounds of the present invention, those having an acidic group or groups can easily form salts by reacting with pharmaceutically acceptable basic compounds. Examples of such basic compounds include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, etc. 
         [0539]    In the compound of the present invention, one or more atoms can be substituted with one or more isotopic atoms. Examples of the isotopic atoms include deuterium ( 2 H), tritium ( 3 H),  13 C,  14 N,  18 O, etc. 
         [0540]    The following is an explanation of pharmaceutical preparations comprising the compound of the present invention as an active ingredient. 
         [0541]    Such pharmaceutical preparations are obtained by formulating the compound of the present invention into usual pharmaceutical preparations, using usually employed diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, etc. 
         [0542]    The form of such pharmaceutical preparations can be selected from various forms according to the purpose of therapy. Typical examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.) and the like. 
         [0543]    To form tablets, any of various known carriers can be used, including, for example, lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose and other excipients; water, ethanol, propanol, simple syrup, glucose solutions, starch solutions, gelatin solutions, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone and other binders; dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogencarbonate, calcium carbonate, aliphatic acid esters of polyoxyethylenesorbitan, sodium laurylsulfate, stearic acid monoglyceride, starch, lactose and other disintegrants; white sugar, stearin, cacao butter, hydrogenated oils and other disintegration inhibitors; quaternary ammonium base, sodium lauryl sulfate and other absorption promoters; glycerin, starch and other wetting agents; starch, lactose, kaolin, bentonite, colloidal silicic acid and other adsorbents; purified talc, stearates, boric acid powder, polyethylene glycol and other lubricants; etc. 
         [0544]    Such tablets may be coated with usual coating materials as required, to prepare, for example, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double- or multi-layered tablets, etc. 
         [0545]    To form pills, any of various known carriers can be used, including, for example, glucose, lactose, starch, cacao butter, hydrogenated vegetable oils, kaolin, talc and other excipients; gum arabic powder, tragacanth powder, gelatin, ethanol and other binders; laminaran, agar and other disintegrants; etc. 
         [0546]    To form suppositories, any of various known carriers can be used, including, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semisynthetic glycerides, etc. 
         [0547]    To form an injection, a solution, emulsion or suspension is sterilized and preferably made isotonic with blood. Any of various known widely used diluents can be employed to prepare the solution, emulsion or suspension. Examples of such diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, aliphatic acid esters of polyoxyethylene sorbitan, etc. In this case, the pharmaceutical preparation may contain sodium chloride, glucose or glycerin in an amount sufficient to prepare an isotonic solution, and may contain usual solubilizers, buffers, analgesic agents, etc., and further, if necessary, coloring agents, preservatives, flavors, sweetening agents, etc., and/or other medicines. 
         [0548]    The proportion of the compound of the present invention in the pharmaceutical preparation is not limited and can be suitably selected from a wide range. It is usually preferable that the pharmaceutical preparation contain the compound of the present invention in a proportion of 1 to 70 wt. %. 
         [0549]    The route of administration of the pharmaceutical preparation according to the present invention is not limited, and the preparation can be administered by a route suitable for the form of the preparation, the patient&#39;s age and sex, the conditions of the disease, and other conditions. 
         [0550]    For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. Injections are intravenously administered singly or as mixed with usual injection transfusions such as glucose solutions, amino acid solutions or the like, or singly administered intramuscularly, intracutaneously, subcutaneously or intraperitoneally, as required. Suppositories are administered intrarectally. 
         [0551]    The dosage of the pharmaceutical preparation is suitably selected according to the method of use, the patient&#39;s age and sex, the severity of the disease, and other conditions, and is usually about 0.001 to about 100 mg/kg body weight/day, and preferably 0.001 to 50 mg/kg body weight/day, in single or divided doses. 
         [0552]    Since the dosage varies depending on various conditions, a dosage smaller than the above range may be sufficient, or a dosage larger than the above range may be required. 
         [0553]    When administered to the human body as a pharmaceutical, the compound of the present invention may be used concurrently with, or before or after, antithrombotics such as blood clotting inhibitors and antiplatelet agents (e.g., warfarin, aspirin, etc.). Further, the present compound may be used concurrently with, or before or after, drugs for treating chronic diseases, such as antihypertensive drugs (ACE inhibitors, beta blockers, angiotensin II receptor antagonists), heart failure drugs (cardiotonic agents, diuretics), and diabetes treatment agents. 
         [0554]    The compound of the present invention has potent blocking effects on human Kv1.5 and/or GIRK1/4 channels, and weak blocking effects on HERG channels. Thus, the compound of the invention has characteristics as an atrial-selective K +  channel-blocking agent. 
         [0555]    Therefore, the compound of the invention can be used as a pharmacologically active substance that is safer and provides a more potent effect on the prolongation of the atrial refractory period than conventional antiarrhythmic agents. The compound of the invention is preferably used as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (elimination of arrhythmia and/or prevention of the occurrence of arrhythmia). The compound of the invention is particularly preferably used as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). The compound of the invention can also be used as a prophylactic agent for thromboembolism such as cerebral infarction and as a therapeutic agent for heart failure. 
         [0556]    The compound having potent blocking effects on both human Kv1.5 and human GIRK1/4 channels has more potent atrial refractory period prolongation effects and is highly safe, compared to compounds inhibiting either one of the channels. Furthermore, this compound has greater therapeutic effects on atrial fibrillation (defibrillation and maintenance of sinus rhythm) than compounds inhibiting either one of the channels. Therefore, the compound having potent blocking effects on both the human Kv1.5 and human GIRK1/4 channels is particularly useful as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (termination of arrhythmia and/or prevention of the occurrence of arrhythmia). This compound is particularly useful as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). 
       3. Third Invention (Benzodiazepine Compound) 
       [0557]    The present inventors conducted extensive research to develop a compound that blocks the I Kur  current (Kv1.5 channel) and/or the I KA C h  current (GIRK1/4 channel) potently and more selectively than other K +  channels. As a result, the inventors found that a novel benzodiazepine compound represented by General Formula (1) below could be the desired compound. The present invention has been accomplished based on the above findings. 
         [0558]    The present invention provides benzodiazepine compounds, and pharmaceutical compositions comprising the benzodiazepine compounds as summarized in items 1 to 7 below. 
         [0559]    Item 1. A benzodiazepine compound represented by General Formula (1): 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    or a salt thereof,
 
wherein R 1 , R 2 , R 3 , and R 4  are each independently hydrogen or lower alkyl; R 2  and R 3  may be linked to form lower alkylene;
 
A 1  is lower alkylene optionally substituted with one or more hydroxyls; and R 5  is an aryl or heterocyclic group, each of which is optionally substituted.
 
         [0560]    Item 2. A pharmaceutical composition comprising a benzodiazepine compound represented by Formula (1) or a salt thereof according to Item 1, and a pharmacologically acceptable carrier. 
         [0561]    Item 3. A pharmaceutical composition according to Item 1 for preventing and/or treating arrhythmia. 
         [0562]    Item 4. A benzodiazepine compound represented by Formula (1) or a salt thereof according to Item 1 for use in the pharmaceutical composition. 
         [0563]    Item 5. Use of a benzodiazepine compound represented by Formula (1) or a salt thereof according to Item 1 as a pharmaceutical composition. 
         [0564]    Item 6. Use of a benzodiazepine compound represented by Formula (1) or a salt thereof according to Item 1 for the production of a pharmaceutical composition. 
         [0565]    Item 7. A method of preventing and/or treating arrhythmia, comprising administering to a patient a benzodiazepine compound represented by Formula (1) or a salt thereof according to Item 1. 
         [0566]    The groups represented by, or substituents of, R 1 , R 2 , R 3 , R 4 , R 5  and A 1  in the specification are described below. 
         [0567]    The term “one or more” may be preferably 1 to 6, and more preferably 1 to 3. 
         [0568]    Examples of “lower alkyl” include linear or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, n-hexyl, isohexyl, and 3-methylpentyl. 
         [0569]    Examples of “lower alkylene” include linear or branched alkylene groups having 1 to 6 carbon atoms, such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, and hexamethylene. 
         [0570]    Examples of “lower alkenylene” include linear or branched alkylene groups having 2 to 6 carbon atoms, such as, ethenylene, propenylene, butenylene, pentenylene, and hexenylene. 
         [0571]    Examples of “cyclo lower alkyl” include linear or branched cyclo alkyl having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 
         [0572]    Examples of “lower alkoxy” include linear or branched alkoxy groups having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy, and 3-methylpentyloxy. 
         [0573]    Examples of “halogen” are fluorine, chlorine, bromine, and iodine. 
         [0574]    Examples of “lower alkylenedioxy” include linear or branched alkylene groups having 1 to 4 carbon atoms, such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy. 
         [0575]    Examples of “lower alkanoyl” include linear or branched alkanoyl groups having 1 to 6 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl. 
         [0576]    Examples of “lower alkoxycarbonyl” include (linear or branched alkoxy having 1 to 6 carbon atoms)carbonyls, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, and tert-butoxycarbonyl. 
         [0577]    Examples of “aralkyl group” include groups wherein aryl groups are substituted on the alkyl groups, such as benzyl and phenethyl. 
         [0578]    Examples of “aryl group” include monocyclic or polycyclic aryl groups, such as phenyl, tolyl, xylyl, and naphthyl. 
         [0579]    Examples of “heterocyclic group” include saturated or unsaturated monocyclic or polycyclic heterocyclic groups containing at least one hetero atom selected from the group consisting of oxygen, sulfur and nitrogen. Examples of preferable heterocyclic groups include the followings (a) to (m) groups: 
         [0580]    (a) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, and its N-oxide, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl (e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.), tetrazolyl (e.g., 1H-tetrazolyl, 2H-tetrazolyl, etc.), dihydrotriazinyl (e.g., 4,5-dihydro-1,2,4-triazinyl, 2,5-dihydro-1,2,4-triazinyl, etc.), etc.; 
         [0581]    (b) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 4 nitrogen atom(s), for example, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, pyrazolidinyl, piperazinyl, etc.; 
         [0582]    (c) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 5 nitrogen atom(s), for example, indolyl, dihydroindolyl (e.g., 2,3-dihydroindolyl, etc.), isoindolyl, indolizinyl, benzimidazolyl, quinolyl, dihydroquinolyl (e.g. 1,4-dihydroquinolyl, etc.), tetrahydroquinolyl (1,2,3,4-tetrahydroquinolyl, etc.), isoquinolyl, dihydroisoquinolyl (e.g., 3,4-dihydro-1H-isoquinolyl, 1,2-dihydroisoquinolyl, etc.), tetrahydroisoquinolyl (e.g., 1,2,3,4-tetrahydro-1H-isoquinolyl, 5,6,7,8-tetrahydroisoquinolyl, etc.), carbostyril, dihydrocarbostyril (e.g., 3,4-dihydrocarbostyril, etc.), indazolyl, benzotriazolyl, tetrazolopyridyl, tetrazolopyridazinyl (e.g., tetrazolo[1,5-b]pyridazinyl, etc.), dihydrotriazolopyridazinyl, imidazopyridyl (e.g., imidazo[1,2-a]pyridyl, imidazo[4,5-c]pyridyl, etc.), naphthyridinyl, cinnolinyl, quinoxalinyl, quinazolinyl, pyrazolopyridyl (e.g., pyrazolo[2,3-a]pyridyl, etc.), etc.; 
         [0583]    (d) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s), for example, furyl, etc.; 
         [0584]    (e) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 3 oxygen atom(s), for example, benzofuryl, dihydrobenzofuryl (e.g. 2,3-dihydrobenzo[b]furyl, etc.), chromanyl, benzodioxanyl (e.g., 1,4-benzodioxanyl, etc.), dihydrobenzoxazinyl (e.g., 2,3-dihydrobenz-1,4-oxazinyl, etc.), benzodioxolyl (benzo[1,3]dioxolyl, etc.), etc.; 
         [0585]    (f) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.), etc.; 
         [0586]    (g) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, morpholinyl, etc.; 
         [0587]    (h) unsaturated condensed 7 to 12-membered heterocyclic groups containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, benzisoxazolyl, furopyridyl (e.g., furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, etc.), etc.; 
         [0588]    (i) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl, isothiazolyl, thiazolinyl, thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,2,3-thiadiazolyl, etc.), etc.; 
         [0589]    (j) saturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl, etc.; 
         [0590]    (k) unsaturated 3- to 8-membered, preferably 5- or 6-membered heteromonocyclic groups containing a sulfur atom, for example, thienyl, etc.; 
         [0591]    (l) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 3 sulfur atom(s), for example, benzothienyl (e.g. benzo[b]thienyl, etc.); and 
         [0592]    (m) unsaturated condensed 7- to 12-membered heterocyclic groups containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolyl, thienopyridyl (e.g., thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, thieno[3,2-c]pyridyl, 4,5-dihydrothieno[3,2-c]pyridyl, thieno[2,3-b]pyridyl, 6,7-dihydrothieno[2,3-b]pyridyl, etc.), imidazothiazolyl (e.g., imidazo[2,1-b]thiazolyl, etc.), dihydroimidazothiazolyl (e.g., 2,3-dihydroimidazo[2,1-b]thiazolyl, etc.), thienopyrazinyl (e.g., thieno[2,3-b]pyrazinyl, etc.), etc.; wherein said heterocyclic groups may be substituted by one or more suitable substituents. 
         [0593]    Substituents of “aryl and heterocyclic group, each of which is optionally substituted” represented by R 5  are each independently one or more substituents selected from the group consisting of: 
         [0000]    (1) oxo;
 
(2) lower alkyl optionally substituted with one or more halogens or heterocyclic groups optionally substituted with one or more substituents selected from the group consisting of lower alkyl; lower alkoxy; lower alkanoyl; lower alkylsulfonyl; hydroxyl; halogen; carboxy; lower alkoxycarbonyl; amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and lower alkylsulfonyl; lower alkyl thio; cyano; and oxo;
 
(3) cyclo lower alkyl;
 
(4) lower alkoxy;
 
(5) aryl optionally substituted with one or more substituents selected from the group consisting of lower alkyl; lower alkoxy; lower alkanoyl; lower alkylsulfonyl; hydroxyl; halogen; carboxy; lower alkoxycarbonyl; amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and lower alkylsulfonyl; lower alkyl thio; and cyano;
 
(6) aralkyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl; lower alkoxy; lower alkanoyl; lower alkylsulfonyl; hydroxyl; halogen; carboxy; lower alkoxycarbonyl; amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and lower alkylsulfonyl; lower alkyl thio; cyano; and oxo;
 
(7) a heterocyclic group optionally substituted with one or more substituents selected from the group consisting of lower alkyl; lower alkoxy; lower alkanoyl; lower alkylsulfonyl; hydroxyl; halogen; carboxy; lower alkoxycarbonyl; amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and lower alkylsulfonyl; lower alkyl thio; cyano; and oxo;
 
(8) hydroxyl;
 
(9) halogen;
 
(10) carboxy;
 
(11) lower alkanoyl;
 
(12) lower alkoxycarbonyl;
 
(13) lower alkylenedioxy;
 
(14) cyano;
 
(15) nitro;
 
(16) sulfo;
 
(17) amino optionally substituted with one or more substituents selected from the group consisting of lower alkyl, lower alkanoyl, and lower alkylsulfonyl;
 
(18) lower alkylsulfonyl; and
 
(19) lower alkyl thio.
 
         [0594]    The “heterocyclic group” in Item (7) above can be selected from the above-mentioned groups (a) to (m). 
         [0595]    Examples of preferable benzodiazepine compounds represented by General Formula (1) include those wherein: 
         [0000]    R 1 , R 2 , R 3 , and R 4  are each independently lower alkyl;
 
A 1  is lower alkylene; and R 5  is piperidyl, piperazinyl, indolyl, benzimidazolyl, 2,3-dihydrobenzimidazolyl, 2,3-dihydroindolyl, furo[2,3-c]pyridyl, 6,7-dihydrofuro[2,3-c]pyridyl, furo[3,2-c]pyridyl, 4,5-dihydrofuro[3,2-c]pyridyl, furo[2,3-b]pyridyl, 6,7-dihydrofuro[2,3-b]pyridyl, thieno[2,3-c]pyridyl, 6,7-dihydrothieno[2,3-c]pyridyl, 1,2,3,4-tetrahydro-1H-isoquinolyl, carbostyril, 3,4-dihydrocarbostyril, quinolyl, 1,4-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, pyrido[3,4-d]imidazolyl, or pyrido[2,3-d]imidazolyl; each of which is optionally substituted with one or more substituents selected from the group consisting of:
 
(1) oxo;
 
(2a) lower (C 1-3 ) alkyl optionally substituted with 6,7-dihydrofuro[2,3-c]pyridyl or 4,5-dihydrofuro[3,2-c]pyridyl, each of which is optionally substituted with one or more substituents selected from the group consisting of oxo and lower alkyl;
 
(4a) C 1-3  alkoxy;
 
(5a) phenyl;
 
(6a) benzyl;
 
(7a) pyridyl optionally substituted with one or more substituents selected from the group consisting of lower alkyl and lower alkoxy;
 
(9) halogen;
 
(10) carboxy;
 
(12a) C 1-3  alkoxycarbonyl; and
 
(13a) C 1-4  alkylenedioxy.
 
         [0596]    The benzodiazepine compound of the present invention represented by Formula (1) or its salt can be readily produced by persons skilled in the art using technical knowledge, based on the Examples and Reference Examples of the present specification. For example, the benzodiazepine compound or its salt can be produced according to the processes shown in the following reaction formulae. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 5 , and A 1  are the same as above, and X 1  is halogen or hydroxyl. 
         [0597]    The reaction of the compound of Formula (2) with the compound of Formula (3) wherein X′ is halogen can be performed in a general inert solvent or without using any solvent in the presence or absence of a basic compound. 
         [0598]    Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower (C 1-6 ) alcohols such as methanol, ethanol, and isopropanol; ketones such as acetone and methyl ethyl ketone; polar solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide, and acetonitrile; and mixed solvents of such solvents. 
         [0599]    The basic compound may be selected from various known compounds. Examples of such compounds include inorganic bases, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, lithium hydrogencarbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; alkali metals such as sodium and potassium; sodium amide; sodium hydride; and potassium hydride; and organic bases, for example, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, and potassium ethoxide; triethylamine; tripropylamine; pyridine; quinoline; 1,5-diazabicyclo[4.3.0]nonene-5 (DBN); 1,8-diazabicyclo[5.4.0]undecene-7 (DBU); and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds can be used singly or in a combination of two or more. 
         [0600]    The above reaction may be performed by adding an alkali metal iodide such as potassium iodide or sodium iodide to the reaction system, as required. 
         [0601]    The compound of Formula (3) is typically used in an amount of at least 0.5 moles, and preferably 0.5 to 10 moles, per mole of the compound of Formula (2). 
         [0602]    The basic compound is typically used in an amount of 0.5 to 10 moles, and preferably 0.5 to 6 moles, per mole of the compound of Formula (2). 
         [0603]    The reaction is typically performed at a temperature of 0° C. to 250° C., and preferably 0° C. to 200° C., and is typically completed in about 1 to about 80 hours. 
         [0604]    The reaction of the compound of Formula (2) with the compound of Formula (3) wherein X 1  is hydroxyl is performed in a suitable solvent in the presence of a condensing agent. 
         [0605]    Examples of solvents usable herein include water; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane; esters such as methyl acetate, ethyl acetate, and isopropyl acetate; alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, and methyl cellosolve; aprotic polar solvents such as acetonitrile, pyridine, acetone, N,N-dimethyl formamide, dimethyl sulfoxide, and hexamethylphosphoric triamide; and mixtures of such solvents. 
         [0606]    Examples of condensing agents include azocarboxylates such as di-tert-butyl azodicarboxylate, N,N,N′,N′-tetramethyl azodicarboxamide, 1,1′-(azodicarbonyl)dipiperidine, diethyl azodicarboxylate; and phosphorus compounds such as triphenylphosphine and tri-n-butylphosphine. 
         [0607]    In this reaction, the compound (3) is typically used in an amount of at least 1 mole, and preferably 1 to 2 moles, per mole of the compound (2). 
         [0608]    The condensing agent is typically used in an amount of at least 1 mole, and preferably 1 to 2 moles, per mole of the compound (2). 
         [0609]    The reaction proceeds typically at 0 to 200° C., and preferably at about 0 to about 150° C., and is completed in about 1 to about 10 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , and A 1  are the same as above; R 5a  is a nitrogen-containing heterocyclic group optionally having substituent(s); and X 2  is a halogen atom. 
         [0610]    Examples of R 5a  include, among groups represented by the group R 5  mentioned above, groups obtained by removing hydrogen from saturated or unsaturated, monocyclic or polycyclic, heterocyclic compounds with an N—H bond, the groups optionally having substituent(s). 
         [0611]    The reaction of the compound of Formula (4) with the compound of Formula (5) can be performed in a general inert solvent or without using any solvent, in the presence or absence of a basic compound. 
         [0612]    Examples of halogen atoms represented by X 2  include chlorine, bromine, iodine, and like atoms. 
         [0613]    Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethylether, diethylene glycol dimethyl ether, and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride; lower alcohols such as methanol, ethanol, and isopropanol; ketones such as acetone and methyl ethyl ketone; polar solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), hexamethylphosphoric triamide, and acetonitrile; and mixtures thereof. 
         [0614]    A wide variety of known basic compounds can be used as the basic compound. Examples of such basic compounds include inorganic bases, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide, and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, lithium hydrogencarbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; alkali metals such as sodium and potassium; sodium amide; sodium hydride; and potassium hydride; and organic bases, for example, alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, and potassium ethoxide; triethylamine; tripropylamine; pyridine; quinoline; 1,5-diazabicyclo[4.3.0]nonene-5 (DBN); 1,8-diazabicyclo[5.4.0]undecene-7 (DBU); and 1,4-diazabicyclo[2.2.2]octane (DABCO). These basic compounds can be used singly or in a combination of two or more. 
         [0615]    The above reaction may be performed by adding as a reaction accelerator an alkali metal iodide such as potassium iodide or sodium iodide to the reaction system, as required. 
         [0616]    The compound of Formula (5) is typically used in an amount of at least 0.5 moles, and preferably about 0.5 to about 10 moles, per mole of the compound of Formula (4). 
         [0617]    The amount of basic compound is typically 0.5 to 10 moles, and preferably 0.5 to 6 moles, per mole of the compound of Formula (4). 
         [0618]    The reaction is typically performed at a temperature of 0 to 250° C., and preferably 0 to 200° C., and is typically completed in about 1 to about 80 hours. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 2 , R 3 , R 4 , and X 2  are as defined above; R 1a  is lower alkyl; R 7  is lower alkoxy; and R 6  is lower alkoxycarbonyl. 
         [0619]    Examples of lower alkyl groups represented by R 1a  include alkyl groups with 1 to 6 carbon atoms, such as methyl, ethyl, and propyl groups. 
         [0620]    Examples of lower alkoxycarbonyl groups represented by R 6  include (C 1-6  alkoxy)carbonyl groups, such as methoxycarbonyl, and ethoxycarbonyl. 
         [0621]    Examples of lower alkoxy groups represented by R 7  include linear or branched alkoxy groups with 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, and butoxy. 
         [0622]    In the reaction of the compound of Formula (7) with the compound of Formula (8), the compound of Formula (7) is reacted with the carboxylic acid compound of Formula (8) through a general amide bond formation reaction. Conditions for known amide bond formation reactions can be easily employed in the amide formation reaction. For example, the following reaction methods can be employed: (i) a mixed acid anhydride method, in which Carboxylic Acid (8) is reacted with an alkyl halocarboxylate to form a mixed acid anhydride, which is then reacted with Amine (7); (ii) an active ester method, in which Carboxylic Acid (8) is converted to an activated ester such as a phenyl ester, p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester or the like, or an activated amide with benzoxazoline-2-thione, and the activated ester or amide is reacted with Amine (7); (iii) a carbodiimide method, in which Carboxylic Acid (8) is subjected to a condensation reaction with Amine (7) in the presence of an activating agent such as dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (WSC), carbonyldiimidazole or the like; and (iv) other methods, for example, a method in which Carboxylic Acid (8) is converted to a carboxylic anhydride using a dehydrating agent such as acetic anhydride, and the carboxylic anhydride is reacted with Amine (7), a method in which an ester of Carboxylic Acid (8) with a lower alcohol is reacted with Amine (7) at a high pressure and a high temperature, and a method in which an acid halide of Carboxylic Acid (8), i.e., a carboxylic acid halide, is reacted with Amine (7). 
         [0623]    Generally, the mixed acid anhydride method (i) is performed in a solvent, in the presence or absence of a basic compound. Any solvents used for conventional mixed acid anhydride methods are usable. Specific examples of usable solvents include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, and carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dimethoxyethane; esters such as methyl acetate, ethyl acetate, and isopropyl acetate; aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, and hexamethylphosphoric triamide; and mixtures thereof. 
         [0624]    Examples of usable basic compounds include organic bases such as triethylamine, trimethylamine, pyridine, dimethylaniline, N-ethyldiisopropylamine, dimethylaminopyridine, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO); inorganic bases, for example, carbonates such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate; metal hydroxides such as sodium hydroxide, potassium hydroxide, and calcium hydroxide; potassium hydride; sodium hydride; potassium; sodium; sodium amide; and metal alcoholates such as sodium methylate and sodium ethylate. 
         [0625]    Examples of alkyl halocarboxylates usable in the mixed acid anhydride method include methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, and isobutyl chloroformate. In this method, Carboxylic Acid (8), an alkyl halocarboxylate, and Amine (7) are preferably used in equimolar amounts, but each of the alkyl halocarboxylate and Carboxylic Acid (8) can also be used in an amount of about 1 to about 1.5 moles per mole of Amine (7). 
         [0626]    The reaction is typically performed at about −20 to about 150° C., and preferably at about 10 to about 50° C., typically for about 5 minutes to about 30 hours, and preferably for about 5 minutes to about 25 hours. 
         [0627]    Method (iii), in which a condensation reaction is performed in the presence of an activating agent, can be performed in a suitable solvent in the presence or absence of a basic compound. Solvents and basic compounds usable in this method include those mentioned hereinafter as solvents and basic compounds usable in the method in which a carboxylic acid halide is reacted with Amine (7) mentioned above as one of the other methods (iv). A suitable amount of activating agent is typically at least 1 mole, and preferably 1 to 5 moles per mole of Compound (7). When WSC is used as an activating agent, addition of 1-hydroxybenzotriazol to the reaction system allows the reaction to proceed advantageously. The reaction is typically performed at about −20 to about 180° C., and preferably at about 0 to about 150° C., and is typically completed in about 5 minutes to about 90 hours. 
         [0628]    When the method in which a carboxylic acid halide is reacted with Amine (7), mentioned above as one of the other methods (iv), is employed, the reaction is performed in the presence of a basic compound in a suitable solvent. Examples of usable basic compounds include a wide variety of known basic compounds, such as those for use in the method (i) above. In addition to those usable in the mixed acid anhydride method, usable solvents include alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, and methylcellosolve; acetonitrile; pyridine; acetone; and water. The ratio of the carboxylic acid halide to Amine (7) is not limited and can be suitably selected from a wide range. It is typically suitable to use, for example, at least about 1 mole, and preferably about 1 to about 5 moles of the carboxylic acid halide per mole of Amine (7). The reaction is typically performed at about −20 to about 180° C., and preferably at about 0 to about 150° C., and typically completed in about 5 minutes to about 30 hours. 
         [0629]    The amide bond formation reaction shown in Reaction Formula 3 above can also be performed by reacting Carboxylic Acid (8) with Amine (7) in the presence of a phosphorus compound serving as a condensing agent, such as triphenylphosphine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric azide, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, or the like. 
         [0630]    The reaction is performed in the presence of a solvent and a basic compound usable for the method in which a carboxylic acid halide is reacted with Amine (7), typically at about −20 to about 150° C., and preferably at about 0 to about 100° C., and is typically completed in about 5 minutes to about 30 hours. It is suitable to use each of the condensing agent and Carboxylic Acid (8) in amounts of at least about 1 mole, and preferably about 1 to about 2 moles, per mole of Amine (7). 
         [0631]    The reaction converting the compound of Formula (9) to the compound of Formula (10) can be performed by, for example, [1] reducing the compound of Formula (9) in a suitable solvent using a catalytic hydrogenation reducing agent, or [2] reducing the compound of Formula (9) in a suitable inert solvent using as a reducing agent such as a mixture of an acid with a metal or metal salt, a mixture of a metal or metal salt with an alkali metal hydroxide, sulfide, or ammonium salt. 
         [0632]    When Method [1] in which a catalytic hydrogenation reducing agent is used, examples of usable solvents are water; acetic acid; alcohols such as methanol, ethanol and isopropanol; hydrocarbons such as n-hexane and cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether and diethylene glycol dimethyl ether; esters such as ethyl acetate and methyl acetate; aprotic polar solvents such as N,N-dimethylformamide; and mixtures thereof. Examples of usable catalytic hydrogenation reducing agents include palladium, palladium black, palladium carbon, platinum carbon, platinum, platinum black, platinum oxide, copper chromite, and Raney nickel. The reducing agent is typically used in an amount of about 0.02 times to about equal to the weight of the compound of Formula (9). The reaction temperature is typically about −20 to about 150° C., and preferably about 0 to about 100° C. The hydrogen pressure is typically about 1 to 10 atm. The reaction is typically completed in about 0.5 to about 100 hours. An acid such as hydrochloric acid may be added to the reaction. 
         [0633]    When Method [2] above is used, a mixture of iron, zinc, tin, or tin (II) chloride with a mineral acid such as hydrochloric acid or sulfuric acid; or a mixture of iron, iron (II) sulfate, zinc, or tin with an alkali metal hydroxide such as sodium hydroxide, a sulfide such as ammonium sulfide, aqueous ammonia solution, or an ammonium salt such as ammonium chloride or the like, can be used as a reducing agent. Examples of inert solvents are water; acetic acid; alcohols such as methanol and ethanol; ethers such as dioxane; and mixtures thereof. Conditions for the reduction reaction can be suitably selected according to the reducing agent to be used. For example, when a mixture of tin (II) chloride and hydrochloric acid is used as a reducing agent, the reaction is advantageously performed at about 0 to about 150° C. for about 0.5 to about 10 hours. A reducing agent is used in an amount of at least 1 mole, and preferably about 1 to 5 moles, per mole of the compound of Formula (9). 
         [0634]    The reaction converting the compound of Formula (10) to the compound of Formula (6b) is performed under the same reaction conditions as those for the reaction of the compound of Formula (7) with the compound of Formula (8). 
         [0635]    The reaction of the compound of Formula (6b) with the compound of Formula (11) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) and the compound of Formula (3) shown in Reaction Formula 1 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , and R 7  are the same as above. 
         [0636]    The reaction of the compound of Formula (12) with the compound of Formula (13) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (7) with the compound of Formula (8) shown in Reaction Formula 3 above. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein R 1 , R 2 , R 3 , R 4 , R 7 , A 1 , and X 2  are the same as above; and X 3  is a halogen atom. 
         [0637]    The reaction converting the compound of Formula (6) to the compound of Formula (2) can be performed in a suitable solvent in the presence of an acid. 
         [0638]    Examples of solvents include water; lower (C 1-6 ) alcohols such as methanol, ethanol, and isopropanol; ethers such as dioxane, tetrahydrofuran, and diethylether; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; polar solvents such as acetonitrile; and mixtures thereof. Examples of acids include mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; aliphatic acids such as formic acid and acetic acid; sulfonic acids such as p-toluenesulfonic acid; Lewis acids such as boron fluoride, aluminium chloride, and boron tribromide; iodides such as sodium iodide and potassium iodide; and 
         [0000]    mixtures of these iodides and Lewis acids. 
         [0639]    The reaction is performed typically at about 0 to about 200° C., and preferably at about 0 to about 150° C., and is typically completed in about 0.5 to about 25 hours. The amount of acid is typically about 1 to about 10 moles, and preferably about 1 to about 2 moles, per mole of the compound of Formula (6). 
         [0640]    Examples of halogen atoms represented by X 3  include chlorine, bromine, iodine, and like atoms. The halogen atom represented by X 3  is preferably one having an atomic number equal to or higher than that of the halogen atom represented by X 2 . 
         [0641]    The reaction of the compound of Formula (2) with the compound of Formula (14) can be performed under the same reaction conditions as those for the reaction of the compound of Formula (2) with the compound of Formula (3) shown in Reaction Formula 1 above, wherein X 1  is a halogen atom. 
         [0642]    The compound of Formula (1) according to the present invention and the starting materials thereof can be produced using a known or conventional synthetic method other than the production method described above. 
         [0643]    In addition, compounds in the form in which a solvate (for example, a hydrate, ethanolate, etc.) was added to the starting material compounds and object compounds shown in each of the reaction formulae are included in each of the formulae. 
         [0644]    The compound of Formula (1) according to the present invention includes stereoisomers and optical isomers. 
         [0645]    The starting material compounds and object compounds represented by each of the reaction formulae can be used in a suitable salt form. 
         [0646]    Each of the object compounds obtained according to the above reaction formulae can be isolated and purified from the reaction mixture by, for example, after cooling the reaction mixture, performing an isolation procedure such as filtration, concentration, extraction, etc., to separate a crude reaction product, and then subjecting the crude reaction product to a general purification procedure such as column chromatography, recrystallization, etc. 
         [0647]    Among the compounds of the present invention, those having a basic group or groups can easily form salts with common pharmaceutically acceptable acids. Examples of such acids include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and other inorganic acids, methansulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malic acid, lactic acid and other organic acids, etc. 
         [0648]    Among the compounds of the present invention, those having an acidic group or groups can easily form salts by reacting with pharmaceutically acceptable basic compounds. Examples of such basic compounds include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, etc. 
         [0649]    In the compound of the present invention, one or more atoms can be substituted with one or more isotopic atoms. Examples of the isotopic atoms include deuterium ( 2 H), tritium ( 3 H),  13 C,  14 N,  18 O, etc. 
         [0650]    The following is an explanation of pharmaceutical preparations comprising the compound of the present invention as an active ingredient. 
         [0651]    Such pharmaceutical preparations are obtained by formulating the compound of the present invention into general pharmaceutical preparations, using typically employed diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, etc. 
         [0652]    The form of such pharmaceutical preparations can be selected from various forms according to the purpose of therapy. Typical examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.) and the like. 
         [0653]    To form tablets, any of various known carriers can be used, including, for example, lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose and other excipients; water, ethanol, propanol, simple syrup, glucose solutions, starch solutions, gelatin solutions, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone and other binders; dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogencarbonate, calcium carbonate, aliphatic acid esters of polyoxyethylenesorbitan, sodium laurylsulfate, stearic acid monoglyceride, starch, lactose and other disintegrants; white sugar, stearin, cacao butter, hydrogenated oils and other disintegration inhibitors; quaternary ammonium base, sodium lauryl sulfate and other absorption promoters; glycerin, starch and other wetting agents; starch, lactose, kaolin, bentonite, colloidal silicic acid and other adsorbents; purified talc, stearates, boric acid powder, polyethylene glycol and other lubricants; etc. 
         [0654]    Such tablets may be coated with general coating materials as required, to prepare, for example, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double- or multi-layered tablets, etc. 
         [0655]    To form pills, any of various known carriers can be used, including, for example, glucose, lactose, starch, cacao butter, hydrogenated vegetable oils, kaolin, talc and other excipients; gum arabic powder, tragacanth powder, gelatin, ethanol and other binders; laminaran, agar and other disintegrants; etc. 
         [0656]    To form suppositories, any of various known carriers can be used, including, for example, polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semisynthetic glycerides, etc. 
         [0657]    To form an injection, a solution, emulsion or suspension is sterilized and preferably made isotonic with blood. Any of various known widely used diluents can be employed to prepare the solution, emulsion or suspension. Examples of such diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, aliphatic acid esters of polyoxyethylene sorbitan, etc. In this case, the pharmaceutical preparation may contain sodium chloride, glucose or glycerin in an amount sufficient to prepare an isotonic solution, and may contain general solubilizers, buffers, analgesic agents, etc., and further, if necessary, coloring agents, preservatives, flavors, sweetening agents, etc., and/or other medicines. 
         [0658]    The proportion of the compound of the present invention in the pharmaceutical preparation is not limited and can be suitably selected from a wide range. It is typically preferable that the pharmaceutical preparation contain the compound of the present invention in a proportion of 1 to 70 wt. %. 
         [0659]    The route of administration of the pharmaceutical preparation according to the present invention is not limited, and the preparation can be administered by a route suitable for the form of the preparation, the patient&#39;s age and sex, the conditions of the disease, and other conditions. 
         [0660]    For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. Injections are intravenously administered singly or as mixed with general injection transfusions such as glucose solutions, amino acid solutions or the like, or singly administered intramuscularly, intracutaneously, subcutaneously or intraperitoneally, as required. Suppositories are administered intrarectally. 
         [0661]    The dosage of the pharmaceutical preparation is suitably selected according to the method of use, the patient&#39;s age and sex, the severity of the disease, and other conditions, and is typically about 0.001 to about 100 mg/kg body weight/day, and preferably 0.001 to 50 mg/kg body weight/day, in single or divided doses. 
         [0662]    Since the dosage varies depending on various conditions, a dosage smaller than the above range may be sufficient, or a dosage larger than the above range may be required. 
         [0663]    When administered to the human body as a pharmaceutical, the compound of the present invention may be used concurrently with, or before or after, antithrombotics such as blood clotting inhibitors and antiplatelet agents (e.g., warfarin, aspirin, etc.). Further, the present compound may be used concurrently with, or before or after, drugs for treating chronic diseases, such as antihypertensive drugs (ACE inhibitors, beta blockers, angiotensin II receptor antagonists), heart failure drugs (cardiotonic agents, diuretics), and diabetes treatment agents. 
         [0664]    The compound of the present invention has potent blocking effects on human Kv1.5 and/or GIRK1/4 channels, and weak blocking effects on HERG channels. Thus, the compound of the invention has characteristics as an atrial-selective K +  channel-blocking agent. 
         [0665]    Therefore, the compound of the invention can be used as a pharmacologically active substance that is safer and provides a more potent effect on the prolongation of the atrial refractory period than conventional antiarrhythmic agents. The compound of the invention is preferably used as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (elimination of arrhythmia and/or prevention of the occurrence of arrhythmia). The compound of the invention is particularly preferably used as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). The compound of the invention can also be used as a prophylactic agent for thromboembolism such as cerebral infarction and as a therapeutic agent for heart failure. 
         [0666]    The compound having potent blocking effects on both human Kv1.5 and human GIRK1/4 channels has more potent atrial refractory period prolongation effects and is highly safe, compared to compounds inhibiting either one of the channels. Furthermore, this compound has greater therapeutic effects on atrial fibrillation (defibrillation and maintenance of sinus rhythm) than compounds inhibiting either one of the channels. Therefore, the compound having potent blocking effects on both the human Kv1.5 and human GIRK1/4 channels is particularly useful as a therapeutic agent for arrhythmia such as atrial fibrillation, atrial flutter, and atrial tachycardia (termination of arrhythmia and/or prevention of the occurrence of arrhythmia). This compound is particularly useful as a therapeutic agent for atrial fibrillation (defibrillation and maintenance of sinus rhythm). 
     
    
     DESCRIPTION OF EMBODIMENTS 
       [0667]    The following Examples are intended to illustrate the present invention in further detail. 
       1. First Invention 
     Reference Example 1 
     Synthesis of 8-methoxy-1-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0668]    Sodium ethoxide (204 mg) was added to an ethanol solution (15 ml) of N-(2-amino-5-methoxyphenyl)-N-methylmalonamic acid ethyl ester (266 mg). The mixture was stirred at 65° C. for 2.5 hours. The reaction liquid was cooled to room temperature, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=1:0→10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (176.3 mg) as a white powder. 
         [0669]      1 H-NMR (CDCl 3 ) δ ppm: 3.36 (2H, s), 3.43 (3H, s), 3.84 (3H, s), 6.79-6.83 (1H, m), 7.06-7.09 (1H, m), and 8.72 (1H, br-s). 
       Reference Example 2 
     Synthesis of 1-ethyl-7-methoxy-5-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0670]    Sodium hydride (60% in oil, 44 mg) was suspended in of DMF (8 ml), and was cooled to 0° C. in an ice water bath. 8-Methoxy-1-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (220 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for an hour. Ethyl iodide (187 mg) was added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1). The purified product was condensed to dryness to give the title compound (190.2 mg) as a yellow solid. 
         [0671]      1 H-NMR (CDCl 3 ) δ ppm: 1.11 (3H, t, J=7.1 Hz), 3.32 (2H, m), 3.59-3.68 (1H, m), 3.85 (3H, s), 4.18-4.30 (1H, m), 6.78 (1H, d, J=2.8 Hz), 6.84 (1H, dd, J=9.0 and 2.8 Hz), 7.26 (1H, d, J=9.0 Hz). 
       Reference Example 3 
     Synthesis of 1-ethyl-7-methoxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0672]    Sodium hydride (60% in oil, 76 mg) was suspended in of DMF (8 ml) 1-ethyl-7-methoxy-5-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (190 mg) was added thereto at 0° C. The mixture was stirred at the same temperaturefor an hour. Methyl iodide (0.19 ml) was added thereto, and the mixture was stirred at room temperature for three days. Water was added to the reaction mixture, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The purified product was condensed to dryness to give the title compound (169 mg) as yellow powder. 
         [0673]      1 H-NMR (CDCl 3 ) δ ppm: 0.86 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.40 (3H, s), 3.65-3.76 (1H, m), 3.85 (3H, s), 4.12-4.24 (1H, m), 6.73 (1H, d, J=2.8 Hz), 6.83 (1H, dd, J=9.0 and 2.8 Hz), and 7.22 (1H, d, J=9.0 Hz). 
       Reference Example 4 
     Synthesis of 7-methoxy-1,3,3,5-tetramethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0674]    Sodium hydride (60% in oil, 128 mg) was suspended in of DMF (10 ml). 8-methoxy-1-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (176 mg) was added thereto at 0° C. The mixture was stirred at the same temperature for an hour. Methyl iodide (0.25 mg) was added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and condensed under reduced pressure. The residue was recrystallized from hexane to give the title compound (161.6 mg) as a white powder. 
         [0675]      1 H-NMR (CDCl 3 ) δ ppm: 0.87 (3H, s), 1.54 (3H, s), 3.40 (3H, s), 3.42 (3H, s), 3.84 (3H, s), 6.73 (1H, s), 6.84 (1H, d, J=8.9 Hz), 7.14 (1H, d, J=8.9 Hz). 
       Reference Example 5 
     Synthesis of 1-ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0676]    1.0M-boron tribromide/dichloromethane solution (1.22 ml) was added to a dichloromethane solution (3 ml) of 1-ethyl-7-methoxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (169 mg) at 0° C. The mixture was stirred at room temperature overnight. Water and methanol were added to the reaction mixture, and extraction was performed using a dichloromethane/methanol mixture (dichloromethane:methanol=10:1). The organic layer was dried over anhydrous sodium sulfate, and condensed to dryness under reduced pressure to give the title compound (156.4 mg) as a white powder. 
         [0677]      1 H-NMR (CDCl 3 ) δ ppm: 0.90 (3H, s), 1.16 (3H, t, J=7.0 Hz), 1.55 (3H, s), 3.41 (3H, s), 3.66-3.78 (1H, m), 4.12-4.23 (1H, m), 6.79 (1H, d, J=2.7 Hz), 6.84 (1H, dd, J=8.8 and 2.7 Hz), 6.88 (1H, s), 7.18 (1H, d, J=8.8 Hz). 
       Reference Example 6 
     Synthesis of 7-hydroxy-1,3,3,5-tetramethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0678]    The synthesis of the title compound was performed in the same manner as in Reference Example 5 using appropriate starting materials.  1 H-NMR (CDCl 3 ) δ ppm: 0.90 (3H, s), 1.49 (3H, s), 3.39 (3H, s), 3.40 (3H, s), 6.73 (1H, d, J=2.7 Hz), 6.80 (1H, dd, J=8.9 and 2.7 Hz), 7.13 (1H, d, J=8.9 Hz). 
       Reference Example 7 
     Synthesis of trifluoromethanesulfonic acid 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl ester 
       [0679]    A dichloromethane solution (50 ml) of 1-ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (2.6 g) was cooled with ice. After adding of triethylamine (1.5 ml) to the solution, trifluoromethane sulfonic anhydride (1.9 ml) was added, and the mixture was stirred at room temperature for 4 hours. Triethylamine (0.75 ml) and trifluoromethane sulfonic anhydride (0.75 ml) were further added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1→5:5). The purified product was condensed to dryness under reduced pressure to give the title compound (3.4 g) as a white solid (yield=860). 
         [0680]      1 H-NMR (CDCl 3 ) δ ppm: 0.87 (3H, s), 1.23 (3H, t, J=7.2 Hz), 1.52 (3H, s), 3.42 (3H, s), 3.81-3.91 (1H, m), 4.04-4.14 (1H, m), 7.15-7.22 (2H, m), 7.40 (1H, d, J=8.9 Hz). 
       Reference Example 8 
     Synthesis of trifluoromethanesulfonic acid 1,5-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepi n-7-yl ester 
       [0681]    The synthesis of the title compound was performed in the same manner as in Reference Example 7 using appropriate starting materials.  1 H-NMR (CDCl 3 ) δ ppm: 3.29 (1H, d, J=12.7 Hz), 3.43 (6H, s), 3.48 (1H, d, J=12.7 Hz), 7.21-7.26 (2H, m), 7.38-7.41 (1H, m). 
       Reference Example 9 
     Synthesis of trifluoromethanesulfonic acid 1,3,3,5-tetramethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl ester 
       [0682]    The synthesis of the title compound was performed in the same manner as in Reference Example 7 using appropriate starting materials.  1 H-NMR (CDCl 3 ) δ ppm: 0.88 (3H, s), 1.56 (3H, s), 3.44 (3H, s), 3.45 (3H, s), 7.16-7.21 (2H, m), 7.33 (1H, d, J=8.9 Hz). 
       Reference Example 10 
     Synthesis of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0683]    Trifluoromethanesulfonic acid 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-yl ester (0.12 g), zinc cyanide (70 mg), tris (dibenzylideneacetone)dipalladium (7 mg), 1,1′-bis (diphenylphosphino) ferrocene (8 mg), and zinc powder (2 mg) were added to DMF (1 ml), and the mixture was heated for 20 minutes at 170° C. (microwave reactor). The reaction liquid was cooled to room temperature, and subjected to celite filtration. The filtrate was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50→0:100). The purified product was condensed under reduced pressure to give the title compound (77 mg) as a white solid. 
         [0684]      1 H-NMR (CDCl 3 ) δ ppm: 0.88 (3H, s), 1.25 (3H, t, J=7.1 Hz), 1.55 (3H, s), 3.44 (3H, s), 3.89-3.95 (1H, m), 4.05-4.11 (1H, m), 7.43 (1H, d, J=9.1 Hz), 7.53-7.56 (2H, m). 
       Reference Example 11 
     Synthesis of 1,5-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0685]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
         [0686]      1 H-NMR (CDCl 3 ) δ ppm: 3.25 (1H, d, J=12.7 Hz), 3.438 (3H, s), 3.444 (3H, s), 3.50 (1H, d, J=12.7 Hz), 7.42 (1H, J=8.4 Hz), 7.57-7.62 (2H, m). 
       Reference Example 12 
     Synthesis of 1,3,3,5-tetramethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0687]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
         [0688]      1 H-NMR (CDCl 3 ) δ ppm: 0.88 (3H, s), 1.56 (3H, s), 3.45 (3H, s), 3.46 (3H, s), 7.34-7.37 (1H, m), 7.53-7.57 (2H, m). 
       Reference Example 13 
     Synthesis of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0689]    1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile (1.0 g) and Raney nickel (3.0 g) were suspended in formic acid (10 ml), and the mixture was stirred at 100° C. for 2 hours. The reaction mixture was filtered to remove insoluble matter, and the filtrate was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:5020:80). The purified product was condensed under reduced pressure to give the title compound (0.92 g) as a yellowish-white solid (yield=92%). 
         [0690]      1 H-NMR (CDCl 3 ) δ ppm: 0.88 (3H, s), 1.26 (3H, t, J=7.1 Hz), 1.56 (3H, s), 3.48 (3H, s), 3.92-3.99 (1H, m), 4.07-4.15 (1H, m), 7.50 (1H, d, J=8.9 Hz), 7.77-7.80 (2H, m), 10.01 (1H, s). 
       Reference Example 14 
     Synthesis of 7-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)but-1-ynyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0691]    Trifluoromethane sulfonic acid 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-yl ester (0.59 g), 2-(but-3-ynyl)isoindol-1,3-dione (0.3 g), dichlorobis(triphenyl phosphine)palladium (II)(53 mg), copper(I) iodide (29 mg), and triethylamine (0.39 ml) were added to DMF (4 ml). The mixture was heated at 150° C. (microwave reactor) for 10 minutes. The reaction liquid was cooled to room temperature, and subjected to celite filtration. The filtrate was condensed under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=60:40→30:70). The purified product was condensed under reduced pressure to give the title compound (0.51 g) as a yellowish-white solid. 
         [0692]      1 H-NMR (CDCl 3 ) δ ppm: 0.84 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.84 (2H, t, J=6.3 Hz), 3.38 (3H, s), 3.68-3.80 (1H, m), 3.99 (2H, t, J=6.3 Hz), 4.00-4.15 (1H, m), 7.19-7.20 (3H, m), 7.73-7.76 (2H, m), 7.87-7.89 (2H, m). 
       Reference Example 15 
     Synthesis of 7-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-prop-1-ynyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0693]    The synthesis of the title compound was performed in the same manner as in Reference Example 14 using appropriate starting materials. 
         [0694]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 3.38 (3H, s), 3.71-3.89 (1H, m), 4.03-4.18 (1H, m) 4.70 (2H, s), 7.20-7.31 (3H, m), 7.75-7.78 (2H, m), 7.90-7.93 (2H, m). 
       Reference Example 16 
     Synthesis of (E)-3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)acrylic acid ethyl ester 
       [0695]    Trifluoromethane sulfonic acid 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl ester (0.40 g), ethyl acrylate (0.13 g), dichlorobis (triphenylphosphine) palladium (II) (35 mg), lithium chloride (64 mg), and triethylamine (0.19 ml) were added to DMF (4 ml). The mixture was heated at 180° C. (microwave reactor) for 20 minutes. The reaction liquid was cooled to room temperature, and subjected to celite filtration. The filtrate was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30→30:70). The purified product was condensed under reduced pressure to give the title compound (0.36 g) as a pale yellow solid. 
         [0696]      1 H-NMR (CDCl 3 ) δ ppm: 0.88 (3H, s), 1.22 (3H, t, J=7.2 Hz), 1.35 (3H, t, J=7.1 Hz), 1.55 (3H, s), 3.44 (3H, s), 3.81-3.90 (1H, m), 4.08-4.25 (1H, m), 4.13 (2H, q, J=7.1 Hz), 6.45 (1H, d, J=16.0 Hz), 7.25-7.27 (1H, m), 7.32-7.37 (2H, m), 7.65 (1H, d, J=16.0 Hz). 
       Reference Example 17 
     Synthesis of 3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl) propionic acid ethyl ester 
       [0697]    10% Palladium on carbon (0.1 g) was added to a methanol solution (10 ml) of (E)-3-(1-ethyl 3,3,5-trimethyl 2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)acrylic acid ethyl ether (0.36 g). The mixture was subjected to catalytic reduction at room temperature and under normal pressure. The catalyst was removed by celite filtration, followed by concentration under reduced pressure to give the title compound (0.29 g) as a brown solid. 
         [0698]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.2 Hz), 1.23 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.65 (2H, t, J=7.5 Hz), 2.98 (2H, t, J=7.5 Hz), 3.40 (3H, s), 3.77-3.90 (1H, m), 4.01-4.21 (3H, m), 7.07-7.11 (2H, m), 7.21-7.26 (1H, m). 
       Reference Example 18 
     Synthesis of 3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)propionic acid 
       [0699]    50% Sodium hydroxide aqueous solution (1 ml) was added to a methanol (20 ml) solution of 3-(1-ethyl 3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epin-7-yl) propionic acid ethyl ester (1.1 g). The mixture was stirred at room temperature overnight. Water was added to the reaction liquid, followed by washing with ether. A hydrochloric acid was added to the aqueous layer, followed by extraction using ethyl acetate and drying using magnesium sulfate. The dried product was condensed under reduced pressure to give the title compound (0.97 g) as a colorless oily matter. 
         [0700]      1 H-NMR(CDCl 3 ) δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.2 Hz), 1.52 (3H, s), 2.72 (2H, t, J=7.5 Hz), 3.00 (2H, t, J=7.5 Hz), 3.40 (3H, s), 3.72-3.88 (1H, m), 4.03-4.21 (1H, m), 7.09-7.13 (2H, m), 7.23-7.26 (1H, m). 
       Reference Example 19 
     Synthesis of 2-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)ethyl carbamic acid tert-butyl ester 
       [0701]    Diphenylphosphoryl azide (1.0 ml) and tert-butanol (10 ml) were added to a THF solution (10 ml) of 3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl) propionic acid (0.97 g) and triethylamine (0.67 ml). The mixture was stirred at 100° C. overnight. The reaction liquid was cooled to room temperature, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=80:20→50:50). The purified product was condensed under reduced pressure to give the title compound (0.38 g) as a colorless oily matter. 
         [0702]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.2 Hz), 1.43 (9H, s), 1.53 (3H, s), 2.83 (2H, t, J=7.1 Hz), 3.38 (2H, t, J=7.1 Hz), 3.41 (3H, s), 3.71-3.85 (1H, m), 4.03-4.19 (1H, m), 4.57 (1H, br), 7.06-7.11 (2H, m), 7.22-7.27 (1H, m). 
       Reference Example 20 
     Synthesis of 5-(2,2-dihydroxyethyl)-5H-furo[3,2-c]pyridin-4-one 
       [0703]    Sodium hydride (60% in oil, 0.36 g) was suspended in DMF (10 ml), and was cooled to 0° C. in an ice water bath. 5H-Furo[3,2-c]pyridin-4-one (1.0 g) was added thereto at the same temperature, and the mixture was stirred at 0° C. for an hour. Bromoacetaldehyde diethylacetal (2.6 ml) was added thereto, and the mixture was stirred at 80° C. for 5 hours. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. A 3N-hydrochrolic acid (5.8 ml) was added to an acetone solution (20 ml) of the residue, and the liquid was stirred at 60° C. for 5 hours. Water was added to the reaction liquid and stirred at room temperature. The precipitated insoluble matter was separated, washed with water, and dried to give the title compound (0.90 g) as a white solid. 
         [0704]      1 H-NMR (DMSO-d 6 ) δ ppm: 3.88 (d, J=5.4 Hz, 2H), 4.95-5.03 (m, 1H), 6.08 (d, J=6.4 Hz, 2H), 6.69 (dd, J=7.4, 0.8 Hz, 1H), 6.94 (dd, J=2.1 and 0.8 Hz, 1H), 7.50 (d, J=7.4 Hz, 1H), 7.86 (d, J=2.1 Hz, 1H). 
       Reference Example 21 
     Synthesis of 5-(2,2-dihydroxy-ethyl)-7-methyl-5H-furo[3,2-c]pyridin-4-one 
       [0705]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0706]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.28 (3H, d, J=1.0 Hz), 3.85 (2H, d, J=5.4 
         [0707]    Hz), 4.95-5.02 (1H, m), 6.06 (2H, d, J=6.3 Hz), 6.95 (1H, d, J=2.1 Hz), 7.33 (1H, d, J=1.0 Hz), 7.90 (1H, d, J=2.1 Hz). 
       Reference Example 22 
     Synthesis of 5-(2,2-dihydroxyethyl)-2-methyl-5H-furo[3,2-c]pyridin-4-one 
       [0708]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0709]      1 H-NMR (DMSO-d 6 ), δ ppm: 2.36 (s, 3H), 3.86 (d, J=5.4 Hz, 2H), 4.94-4.98 (m, 1H), 6.04 (d, J=6.4 Hz, 2H), 6.52 (s, 1H), 6.59 (d, J=7.4 Hz, 1H), 7.41 (d, J=7.4 H, 1H). 
       Reference Example 23 
     Synthesis of 5-(2,2-dihydroxyethyl)-2,3-dimethyl-5H-furo[3,2-c]pyridin-4-one 
       [0710]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0711]      1 H-NMR (DMSO-d 6 ), δ ppm: 2.18 (3H, s), 2.28 (3H, s), 3.84 (2H, d, J=5.4 Hz), 4.95-5.02 (1H, m), 6.04 (2H, d, J=6.2 Hz), 6.53 (1H, d, J=7.4 Hz), 7.38 (1H, d, J=7.4 Hz). 
       Reference Example 24 
     Synthesis of 5-(2,2-dihydroxyethyl)-2,7-dimethyl-5H-furo[3,2-c]pyridin-4-one 
       [0712]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0713]      1 H-NMR (DMSO-d 6 ), δ ppm: 2.14 (3H, s), 2.39 (3H, s), 3.82 (2H, d, J=5.4 Hz), 4.95-5.01 (1H, m), 6.10 (2H, d, J=6.2 Hz), 6.55 (1H, s), 7.24 (1H, s). 
       Reference Example 25 
     Synthesis of 6-(2,2-dihydroxyethyl)-4-methyl-6H-furo[2,3-c]pyridin-7-one 
       [0714]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0715]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.17 (3H, s), 3.86 (2H, d, J=5.4 Hz), 4.95-5.01 (1H, m), 6.06 (2H, d, J=6.2 Hz), 6.92 (1H, d, J=1.8 Hz), 7.17 (1H, s), 8.10 (1H, d, J=1.8 Hz). 
       Reference Example 26 
     Synthesis of 5-(2,2-dihydroxyethyl)-5H-thieno[3,2-c]pyridin-4-one 
       [0716]    The synthesis of the title compound was performed in the Same manner as in Reference Example 20 using appropriate starting materials. 
         [0717]      1 H-NMR (DMSO-d 6 ) δ ppm: 3.90 (d, J=6.3 Hz, 2H), 4.99-5.04 (m, 1H), 6.07 (d, J=6.3 Hz, 2H), 6.86 (d, J=7.2 Hz, 1H), 7.41-7.49 (m, 2H), 7.57-7.64 (m, 1H). 
       Reference Example 27 
     Synthesis of 6-(2,2-dihydroxyethyl)-6H-thieno[2,3-c]pyridin-7-one 
       [0718]    The synthesis of the title compound was performed in the same manner as in Reference Example 20 using appropriate starting materials. 
         [0719]      1 H-NMR (DMSO-d 6 ), δ ppm: 3.98 (d, J=5.3 Hz, 2H), 5.11-5.16 (m, 1H), 6.04 (d, J=6.4 Hz, 1H), 6.66 (d, J=7.1 Hz, 2H), 7.27 (d, J=5.2 Hz, 1H), 7.41 (d, J=7.1 Hz, 1H), 7.84 (d, J=5.2 H, 1H). 
       Reference Example 28 
     (1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-acetonitrile 
       [0720]    To a solution of 7-chloromethyl-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.11 g) in DMF (15 ml) was added sodium cyanide (0.59 g) at room temperature, the mixture was stirred overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with magnesium sulfate, and was condensed under reduced pressure to give the title compound (0.84 g) as a pale yellow oil. 
         [0721]      1 H NMR (CDCl 3 ), δ ppm: δ 0.85 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.54 (3H, s), 3.43 (3H, s), 3.77-3.86 (3H, m), 4.09-4.19 (1H, m), 7.21-7.24 (2H, m), 7.34 (1H, d, J=8.3 Hz). 
       Reference Example 29 
     2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-2-methyl-propionitrile 
       [0722]    (1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-acetonitrile (0.84 g) was dissolved in DMF (20 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 0.259 g) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (0.405 ml) was added thereto, and the mixture was stirred at room temperature overnight. Methanol was added to the reaction mixture, and the mixture was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1). The purified product was condensed to dryness under reduced pressure to give the title compound (0.9 g) as a white powder. 
         [0723]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.20 (3H, t, J=7.06 Hz), 1.54 (3H, s), 1.77 (6H, s), 3.45 (3H, s), 3.78-3.87 (1H, m), 4.09-4.18 (1H, m), 7.34 (3H, s). 
       Reference Example 30 
     1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carboxylic acid 
       [0724]    To a t-butanol (20 ml) H2O (5 ml) solution of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (2.25 g) and 2-methyl-2-butene (3.25 ml) were added sodium dihydrogenphosphate (0.92 g) and sodium chlorite (2.081 g), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure to give the title compound (0.98 g) as a white powder. 
       mp: 296-299° C. 
     Reference Example 31 
     7-Bromomethyl-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]di azepine-2,4-dione 
       [0725]    Lithium bromide (0.678 g) was added to an THF solution (2.3 ml) of 7-chloromethyl-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]d iazepine-2,4-dione (0.23 g), and the mixture was stirred at room temperature overnightr. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with magnesium sulfate, and was condensed under reduced pressure to give the title compound (0.24 g) as a white solid. 
         [0726]      1 H NMR (CDCl 3 ), δ ppm: 0.85 (3H, s), 1.20 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.43 (3H, s), 3.77-3.87 (1H, m), 4.08-4.17 (1H, m), 4.49 (2H, s), 7.28-7.29 (3H, m). 
       Reference Example 32 
     1-Ethyl-7-(3-hydroxy-propyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [0727]    3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)propionic acid (1.0 g) was dissolved in THF (20 ml) and was cooled to 0° C. in ice water bath. Triethylamine (0.525 ml) and ethyl chloroformate (0.325 ml) were added to this solution and stirred for 30 minutes at same temperature. Sodium borohydride (0.36 g) was added to the mixture under cooling in ice methanol bath. Methanol (0.64 ml) was added dropwise to the mixture and stirred for 1 hour at same temperature. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with magnesium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1). The purified product was condensed to dryness under reduced pressure to give the title compound (0.71 g) as a colorless oil. 
         [0728]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.88-1.95 (2H, m), 2.76 (2H, t, J=7.8 Hz), 3.41 (3H, s), 3.71 (2H, t, J=6.3 Hz), 3.74-3.83 (1H, m), 4.10-4.19 (1H, m), 7.07 (1H, d, J=1.8 Hz), 7.11 (1H, dd, J=8.3 and 1.8 Hz), 7.23 (1H, d, J=8.3 Hz) 
       Reference Example 33 
     1-(2-Methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0729]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 184-185° C. 
     Reference Example 34 
     1-Isobutyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0730]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 204-205° C. 
     Reference Example 35 
     1-(2-Methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0731]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 163-166° C. 
     Reference Example 36 
     1-Isobutyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0732]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 154-155° C. 
     Reference Example 37 
     1-Cyclopropyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0733]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
         [0734]      1 H NMR (CDCl 3 ), δ ppm: 0.43 (2H, br), 1.07 (2H, br), 1.66 (3H, br), 3.17-3.23 (1H, m), 7.35 (1H, br), 7.50-7.56 (2H, m), 8.67 (1H, br). 
       Reference Example 38 
     1-Cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0735]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
         [0736]      1 H NMR (CDCl 3 ), δ ppm: 0.22-0.23 (2H, m), 0.46-0.48 (2H, m), 0.98-1.07 (1H, m), 3.90 (1H, br-d), 7.38-7.54 (3H, m), 9.42 (1H, br). 
       Reference Example 39 
     1-Cyclopropyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0737]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0738]      1 H NMR (CDCl 3 ), δ ppm: 0.44 (2H, br), 1.08 (2H, br), 1.30 (6H, br), 3.20-3.25 (1H, m), 7.49 (1H, d, J=1.8 Hz), 7.58 (1H, d, J=8.4 Hz), 7.78 (1H, dd, J=8.4, 1.8 Hz), 9.98 (1H, s). 
       Reference Example 40 
     1-Cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0739]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 124-125° C. 
     Reference Example 41 
     1-Cyclopropyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0740]    1-(2-Methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile (1.0 g) was dissolved in DMF (10 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 0.167 g) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (0.261 ml) was added thereto, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and was cooled to 0° C. in ice water bath. The precipitated insoluble matter was separated and dried to give the title compound (0.61 g) as a white powder. 
         [0741]      1 H NMR (CDCl 3 ), δ ppm: 0.10-0.17 (1H, m), 0.66-0.73 (1H, m), 0.82-0.92 (1H, m), 0.89 (3H, s), 1.21-1.29 (1H, m), 1.55 (3H, s), 3.16-3.22 (1H, m), 3.41 (3H, s), 7.50-7.57 (3H, m). 
       Reference Example 42 
     1-Isobutyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0742]    The synthesis of the title compound was performed in the same manner as in Reference Example 41 using appropriate starting materials. 
         [0743]      1 H NMR (CDCl 3 ), δ ppm: 0.72 (3H, d, J=6.7 Hz), 0.75 (3H, d, J=6.7 Hz), 0.86 (3H, s), 1.55 (3H, s), 1.77-1.88 (1H, m), 3.35 (1H, dd, J=13.7, 6.6 Hz), 3.45 (3H, s), 4.40 (1H, dd, J=13.7, 8.4 Hz), 7.41 (1H, d, J=8.4 Hz), 7.53-7.57 (2H, m). 
       Reference Example 43 
     1-(2-Methoxy-ethyl)-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0744]    The synthesis of the title compound was performed in the same manner as in Reference Example 41 using appropriate starting materials. 
         [0745]      1 H NMR (CDCl 3 ), δ ppm: 0.89 (3H, s), 1.55 (3H, s), 3.32 (3H, s), 3.43 (3H, s), 3.59 (1H, ddd, J=10.4, 5.0, 3.7 Hz), 3.75 (1H, ddd, J=10.4, 7.8, 3.4 Hz), 3.94 (1H, ddd, J=14.4, 7.8, 3.7 Hz), 4.12 (1H, ddd, J=14.4, 5.0, 3.4 Hz), 7.52-7.55 (2H, m), 7.81-7.84 (1H, m). 
       Reference Example 44 
     5-Cyclopropyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0746]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 252-253° C. 
     Reference Example 45 
     5-Isobutyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0747]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 219-220° C. 
     Reference Example 46 
     5-Cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0748]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 234-236° C. 
     Reference Example 47 
     5-(2-Methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0749]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 247-248° C. 
     Reference Example 48 
     Methanesulfonic acid 3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-propyl ester 
       [0750]    The synthesis of the title compound was obtained from 1-ethyl-7-(3-hydroxypropyl)-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tet rahydro-1H-benzo[b][1,4]diazepine and methanesulfonyl chloride in a conventional matter. 
         [0751]      1 H NMR (CDCl 3 ), δ ppm: 0.86 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.05-2.16 (2H, m), 2.79 (2H, t, J=7.6 Hz), 3.03 (3H, s), 3.42 (3H, s), 3.74-3.83 (1H, m), 4.10-4.18 (1H, m), 4.26 (2H, t, J=6.2 Hz), 7.07 (1H, dd, J=8.3 and 2.0 Hz), 7.10 (1H, d, J=2.0 Hz), 7.25 (1H, d, J=8.3 Hz). 
       Reference Example 49 
     1-Cyclopropyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0752]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0753]      1 H NMR (CDCl 3 ), δ ppm: 0.10-0.20 (1H, m), 0.66-0.73 (1H, m), 0.73-0.94 (1H, m), 0.89 (3H, s), 1.21-1.28 (1H, m), 1.55 (3H, s), 3.91-3.45 (1H, m), 3.45 (3H, s), 7.57 (1H, d, 8.4 Hz), 7.74 (1H, d, J=1.8 Hz), 7.79 (1H, dd, J=8.4, 1.8 Hz), 10.01 (1H, s). 
       Reference Example 50 
     1-Isobutyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0754]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0755]      1 H NMR (CDCl 3 ), δ ppm: 0.71 (3H, d, J=6.7 Hz), 0.75 (3H, d, J=6.7 Hz), 0.86 (3H, s), 1.53 (3H, s), 1.76-1.90 (1H, m), 3.39 (1H, dd, J=13.6, 6.6 Hz), 3.49 (3H, s), 4.42 (1H, dd, J=13.6, 8.4 Hz), 7.47 (1H, d, J=9.0 Hz), 7.76-7.79 (2H, m), 10.01 (1H, s). 
       Reference Example 51 
     1-(2-Methoxy-ethyl)-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0756]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0757]      1 H NMR (CDCl 3 ), δ ppm: 0.88 (3H, s), 1.55 (3H, s), 3.31 (3H, s), 3.48 (3H, s), 3.60 (1H, ddd, J=10.4, 5.2, 4.1 Hz), 3.74 (1H, ddd, J=10.4, 7.1, 4.1 Hz), 4.01-4.15 (2H, m), 7.75-7.78 (2H, m), 7.80-7.83 (1H, m), 10.01 (1H, s). 
       Reference Example 52 
     5-Isobutyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0758]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 208-211° C. 
     Reference Example 53 
     5-Cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0759]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 183-188° C. 
     Reference Example 54 
     1,3,3-Trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epine-7-carbonitrile 
       [0760]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 289-294° C. 
     Reference Example 55 
     1-Ethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4 ]diazepine-7-carbonitrile 
       [0761]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 215-218° C. 
     Reference Example 56 
     3,3,5-Trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epine-7-carbonitrile 
       [0762]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 250-251° C. 
     Reference Example 57 
     5-Ethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4 ]diazepine-7-carbonitrile 
       [0763]    The synthesis of the title compound was performed in the same manner as in Reference Example 10 using appropriate starting materials. 
       mp: 241-247° C. 
     Reference Example 58 
     1,3,3-Trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epine-7-carbaldehyde 
       [0764]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 208-210° C. 
     Reference Example 59 
     1-Ethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4 ]diazepine-7-carbaldehyde 
       [0765]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0766]      1 H NMR (CDCl 3 ), δ ppm: 1.07 (3H, br), 1.29 (3H, t, J=7.1 Hz), 1.57 (3H, br), 4.57 (2H, q, J=7.1 Hz), 7.50 (1H, d, J=8.5 Hz), 7.57 (1H, br), 7.77 (1H, dd, J=8.5, 1.8 Hz), 8.42 (1H, br). 9.99 (1H, s). 
       Reference Example 60 
     3,3,5-Trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diaz epine-7-carbaldehyde 
       [0767]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 197-202° C. 
     Reference Example 61 
     5-Ethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4 ]diazepine-7-carbaldehyde 
       [0768]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
       mp: 188-191° C. 
     Reference Example 62 
     5-Cyclopropylmethyl-1-(2-methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0769]    The synthesis of the title compound was performed in the same manner as in Reference Example 41 using appropriate starting materials. 
         [0770]      1 H NMR (CDCl 3 ), δ ppm: 0.15-0.24 (2H, m), 0.38-0.51 (2H, m), 0.87 (3H, s), 0.93-1.01 (1H, m), 1.55 (3H, s), 3.32 (3H, s), 3.53-3.62 (1H, m), 3.73-3.79 (1H, m), 3.97-4.04 (1H, m), 4.06-4.13 (1H, m), 7.55 (1H, dd, J=8.5, 1.9 Hz), 7.66 (1H, d, J=1.9 Hz), 7.82 (1H, d, J=8.5 Hz). 
       Reference Example 63 
     1-Cyclopropylmethyl-5-(2-methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0771]    The synthesis of the title compound was performed in the same manner as in Reference Example 41 using appropriate starting materials. 
         [0772]      1 H NMR (CDCl 3 ), δ ppm: 0.14-0.22 (2H, m), 0.38-0.49 (2H, m), 0.87 (3H, s), 0.93-1.02 (1H, m), 1.55 (3H, s), 3.34 (3H, s), 3.53-3.65 (1H, m), 3.77-3.83 (1H, m), 3.91-3.98 (1H, m), 4.05-4.13 (1H, m), 7.45 (1H, d, J=8.5 Hz), 7.53 (1H, dd, J=8.5, 1.9 Hz), 8.10 (1H, d, J=1.9 Hz). 
       Reference Example 64 
     5-Cyclopropyl-1-cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile 
       [0773]    The synthesis of the title compound was performed in the same manner as in Reference Example 41 using appropriate starting materials. 
         [0774]      1 H NMR (CDCl 3 ), δ ppm: 0.03-0.19 (3H, m), 0.27-0.41 (2H, m), 0.61-0.68 (1H, m), 0.81-0.93 (1H, m), 0.88 (3H, s), 1.21-1.29 (2H, m), 1.54 (3H, s), 3.06-3.26 (1H, m), 3.42 (1H, dd, J=14.3, 6.8 Hz), 4.31 (1H, dd, J=14.3, 7.5 Hz), 7.38 (1H, d, J=8.5. Hz), 7.53 (1H, dd, J=8.5, 1.8 Hz), 7.72 (1H, d, J=1.8 Hz). 
       Reference Example 65 
     5-Cyclopropylmethyl-1-(2-methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0775]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0776]      1 H NMR (CDCl 3 ), δ ppm: 0.13-0.25 (2H, m), 0.37-0.48 (2H, m), 0.87 (3H, s), 0.96-1.03 (1H, m), 1.55 (3H, s), 3.32 (3H, s), 3.54-3.59 (1H, m), 3.66 (1H, dd, J=14.2, 6.4 Hz), 3.75 (1H, ddd, J=10.3, 7.2, 4.7 Hz), 4.04-4.19 (3H, m), 7.78 (1H, dd, J=8.4, 1.7 Hz), 7.82 (1H, d, J=8.4 Hz), 7.88 (1H, d, J=1.7 Hz), 10.0 (1H, s). 
       Reference Example 66 
     1-Cyclopropylmethyl-5-(2-methoxy-ethyl)-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0777]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0778]      1 H NMR (CDCl 3 ), δ ppm: 0.14-0.24 (2H, m), 0.38-0.50 (2H, m), 0.87 (3H, s), 0.97-1.07 (1H, m), 1.55 (3H, s), 3.33 (3H, s), 3.53-3.59 (1H, m), 3.65 (1H, dd, J=14.2, 6.4 Hz), 3.73-3.79 (1H, m), 4.03-4.16 (3H, m), 7.51 (1H, d, J=8.4 Hz), 7.79 (1H, dd, J=8.4, 1.9 Hz), 8.19 (1H, d, J=1.9 Hz), 10.0 (1H, s). 
       Reference Example 67 
     5-Cyclopropyl-1-cyclopropylmethyl-3,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde 
       [0779]    The synthesis of the title compound was performed in the same manner as in Reference Example 13 using appropriate starting materials. 
         [0780]      1 H NMR (CDCl 3 ), δ ppm: 0.09-0.07 (1H, m), 0.09-0.20 (2H, m), 0.27-0.40 (2H, m), 0.62-0.68 (1H, m), 0.83-0.92 (1H, m), 0.88 (3H, s), 1.20-1.28 (2H, m), 1.54 (3H, s), 3.27-3.33 (1H, m), 3.45 (1H, dd, J=14.3, 6.8 Hz), 4.34 (1H, dd, J=14.3, 7.5 Hz), 7.43 (1H, d, J=8.4 Hz), 7.77 (1H, dd, J=8.4, 1.9 Hz), 7.92 (1H, d, J=1.9 Hz), 10.0 (1H, s). 
       Example 1 
     Synthesis of 7-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl) butyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0781]    10% Palladium on carbon (0.52 g) was added to a methanol solution (50 ml) of 7-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl) but-1-ynyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (2.2 g). The mixture was subjected to catalytic reduction at room temperature under normal pressure. The catalyst was removed by celite filtration, followed by concentration under reduced pressure to give the title compound (1.93 g) as a brown solid. 
         [0782]      1 H-NMR (CDCl 3 ) δ ppm: 0.81 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.61-1.79 (4H, m), 2.68 (2H, t, J=7.0 Hz), 3.40 (3H, s), 3.71-3.81 (3H, m), 4.01-4.18 (1H, m), 7.02-7.08 (2H, m), 7.20 (1H, d, J=8.3 Hz), 7.70-7.74 (2H, m), 7.83-7.86 (2H, m). 
       Example 2 
     Synthesis of 7-(4-aminobutyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0783]    Hydrazine hydrate (0.5 ml) was added to a methanol solution (60 ml) of 7-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl) butyl]-1-ethyl-3,3,5-tri methyl-1,5-dihydrobenzo[b][1,4]diazepine 2,4-dione (1.93 g). The mixture was stirred for 5.5 hours while heated under reflux. After cooled to room temperature, a 1N-sodium hydroxide aqueous solution was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and condensed under reduced pressure to give the title compound (1.2 g) as a yellow solid. 
         [0784]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.47-1.58 (2H, m), 1.52 (3H, s), 1.62-1.73 (4H, m), 2.66 (2H, t, J=7.6 Hz), 2.76 (2H, t, J=7.0 Hz), 3.41 (3H, s), 3.71-3.84 (1H, m), 4.03-4.18 (1H, m), 7.02-7.09 (2H, m), 7.21 (1H, d, J=8.3 Hz). 
       Example 3 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{4-[(pyridin-4-ylmethyl)amino]butyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0785]    4-Pyridine carbaldehyde (0.15 ml) was added to a methanol solution (10 ml) of 7-(4-aminobutyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.51 g). The mixture was stirred for an hour at room temperature under nitrogen atmosphere. Sodium borohydride (0.2 g) was added to the mixture, and the mixture was stirred at room temperature overnight. The liquid was then condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→3:2). The purified product was condensed under reduced pressure to give the title compound (0.38 g) as a colorless oily matter. 
         [0786]      1 H-NMR (CDCl 3 ) δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.47-1.58 (2H, m), 1.53 (3H, s), 1.53-1.60 (2H, m), 1.62-1.71 (2H, m), 2.62-2.68 (4H, m), 3.40 (3H, s), 3.69-3.81 (3H, m), 4.03-4.19 (1H, m), 7.01 (1H, d, J=1.9 Hz), 7.06 (1H, dd, J=8.3, 1.9 Hz), 7.21 (1H, d, J=8.3 Hz), 7.25-7.28 (2H, m), 8.53-3.56 (2H, m). 
       Example 4 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(4-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}butyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0787]    (2-Methyl-4-oxo-4H-furo[3,2-c]pyridin 5-yl)acetaldehyde (0.18 g) and acetic acid (0.1 ml) were added to a 1,2-dichloroethane solution (5 ml) of 1-ethyl-3,3,5-trimethyl-7-{4-[(pyridin-4-ylmethyl)amino]butyl}-1,5-dihydrobenzo[b][1,4]diazepine 2,4-dione (0.38 g). The mixture was stirred for 30 minutes at room temperature. sodium triacetoxyborohydride (0.32 g) was added to the mixture, and the mixture was stirred at room temperature overnight. The reaction mixture was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→9:1). The purified product was condensed under reduced pressure. A 6N-hydrogen chloride ethyl acetate solution (1.0 ml) was added to an ethyl acetate solution (20 ml) of the residue, and the liquid was stirred at room temperature. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (0.43 g) as a white solid. 
         [0788]      1 H-NMR (DMSOd 6 ) δ ppm: 0.69 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.30 (3H, s), 1.56 (2H, br), 1.76 (2H, br), 2.38 (3H, s), 2.59 (2H, t, J=7.6 Hz), 3.13 (2H, br), 3.31 (3H, s), 3.22-3.38 (2H, m), 3.40-3.55 (1H, m), 3.99-4.08 (1H, m), 4.42 (2H, br), 4.64 (2H, br), 6.56 (1H, s), 6.75 (1H, d, J=7.4 Hz), 7.13 (1H, d, J=8.4 Hz), 7.25 (1H, s), 7.38 (1H, d, J=8.4 Hz), 7.63 (1H, br), 8.22 (2H, br), 8.92 (2H, br). 
       Example 5 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[4-[(2-methylpyridin-3-ylmethyl)amino] b  utyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0789]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0790]      1 H-NMR (CDCl 3 ) δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.52-1.61 (2H, m), 1.63-1.70 (2H, m), 2.56 (3H, s), 2.62-2.73 (4H, m), 3.40 (3H, s), 3.68-3.81 (3H, m), 4.02-4.19 (1H, m), 7.01-7.11 (3H, m), 7.20 (1H, d, J=8.3 Hz), 7.58-7.61 (1H, m), 8.38-8.40 (1H, m). 
       Example 6 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(4-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}butyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0791]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0792]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.31 (3H, s), 1.59 (2H, br), 1.74 (2H, br), 2.50 (3H, s), 2.61 (2H, t, J=7.6 Hz), 2.80 (2H, br), 3.10 (2H, br), 3.31 (3H, s), 3.55-3.70 (1H, m), 3.95-4.08 (1H, m), 4.37 (4H, br), 6.56 (1H, s), 6.82 (1H, br), 6.95 (1H, s), 7.13 (1H, d, J=8.4 Hz), 7.25 (1H, s), 7.39 (1H, d, J=8.4 Hz), 7.68 (1H, br), 7.81 (1H, br), 7.91 (1H, br), 8.71 (2H, br). 
       Example 7 
     Synthesis of 7-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [0793]    The synthesis of the title compound was performed in the same manner as in Example 1 using appropriate starting materials. 
         [0794]      1 H NMR (CDCl 3 ) δ ppm: 0.80 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.00-2.13 (2H, m), 2.72 (2H, t, J=7.7 Hz), 3.42 (3H, s), 3.68-3.73 (3H, m), 3.98-4.11 (1H, m), 7.07-7.10 (2H, m), 7.17-7.20 (1H, m), 7.70-7.75 (2H, m), 7.82-7.85 (2H, m). 
       Example 8 
     Synthesis of 7-(3-aminopropyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione 
       [0795]    The synthesis of the title compound was performed in the same manner as in Example 2 using appropriate starting materials. 
         [0796]      1 H NMR (CDCl 3 ) δ ppm: 0.84 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.54 (3H, s), 1.76 (2H, br), 1.74-1.91 (2H, m), 2.71 (2H, t, J=8.2 Hz), 2.84 (2H, t, J=7.0 Hz), 3.42 (3H, s), 3.81-3.95 (1H, m), 4.08-4.19 (1H, m), 7.09-7.14 (2H, m), 7.22-7.26 (1H, m). 
       Example 9 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{3-[(pyridin-4-ylmethyl)amino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0797]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0798]      1 H NMR (CDCl 3 ) δ ppm: 0.81 (3H, s), 1.20 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.78-1.91 (2H, m), 2.66-2.74 (4H, m), 3.39 (3H, s), 3.71-3.89 (3H, m), 4.05-4.16 (1H, m), 7.02-7.10 (3H, m), 7.19-7.26 (2H, m), 8.52-8.56 (2H, m). 
       Example 10 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(3-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0799]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0800]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.69 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.05 (2H, br), 2.38 (3H, s), 2.60 (2H, br), 3.04 (2H, br), 3.31 (3H, s), 3.25-3.50 (2H, m), 3.40-3.65 (1H, m), 3.91-4.08 (1H, m), 4.38 (2H, br), 4.58 (2H, br), 6.55 (1H, s), 6.75 (1H, d, J=7.4 Hz), 7.13 (1H, d, J=8.4 Hz), 7.25 (1H, s), 7.38 (1H, d, J=8.4 Hz), 7.63 (1H, d, J=7.4 Hz), 8.17 (2H, br), 8.88 (2H, br). 
       Example 11 
     Synthesis of 7-(2-aminoethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [0801]    A 4N-hydrogen chloride ethyl acetate solution (6 ml) was added to an ethyl acetate solution (20 ml) of [2-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-yl)ethyl]carbamic acid tert-butyl ester (0.38 g), and the mixture was stirred at room temperature overnight. The reaction mixture was condensed under reduced pressure to give the title compound (0.26 g) as a pale orange amorphous solid. 
         [0802]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.39 (3H, s), 2.91-3.00 (2H, m), 3.02-3.13 (2H, m), 3.38 (3H, s), 3.68-3.83 (1H, m), 3.95-4.11 (1H, m), 7.11-7.16 (1H, m), 7.23 (1H, br), 7.31-7.35 (1H, m), 8.06 (3H, br). 
       Example 12 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{2-[(pyridin-4-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0803]    Triethylamine (0.1 ml) and 4-pyridine carbaldehyde (0.094 ml) were added to a methanol solution (10 ml) of 7-(2-aminoethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine 2,4-dione hydrochloride (0.26 g). The mixture was stirred at room temperature for 1 hour. Sodium borohydride (0.11 g) was added, and the mixture was further stirred at room temperature overnight. The reaction liquid was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→3:2). The purified product was condensed under reduced pressure to give the title compound (0.21 g) as a colorless oily matter. 
         [0804]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.86 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.82-2.94 (4H, m), 3.40 (3H, s), 3.73-3.85 (1H, m), 3.84 (2H, s), 4.02-4.18 (1H, m), 7.05-7.11 (2H, m), 7.20-7.26 (3H, m), 8.52-8.55 (2H, m). 
       Example 13 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{2-[(2-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0805]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0806]      1 H-NMR (CDCl 3 ) δ ppm: 0.82 (3H, s), 1 18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.52 (3H, s), 2.82-2.88 (2H, m), 2.93-2.99 (2H, m), 3.40 (3H, s), 3.75-3.82 (1H, m), 3.81 (3H, s), 4.11-4.18 (1H, m), 7.06-7.12 (2H, m), 7.22-7.26 (2H, m), 7.53-7.57 (1H, m), 8.37-8.40 (1H, m). 
       Example 14 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{2-[(4-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0807]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0808]      1 H-NMR (CDCl 3 ) δ ppm: 0.82 (3H, s), 1 18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.33 (3H, s), 2.82-2.87 (2H, m), 2.93-2.99 (2H, m), 3.39 (3H, s), 3.75-3.84 (1H, m), 3.82 (3H, s), 4.10-4.20 (1H, m), 7.06-7.12 (3H, m), 7.21-7.26 (1H, m), 8.38 (1H, d, J=4.9 Hz), 8.41 (1H, s). 
       Example 15 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(2-{N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}ethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride. 
       [0809]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0810]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.69 (3H, s), 1.02 (3H, t, J=7.1 Hz), 1.31 (3H, s), 2.39 (3H, s), 3.08 (2H, br), 3.29 (3H, s), 3.11-3.42 (2H, m), 3.42-3.70 (3H, m), 3.91-4.10 (1H, m), 4.36 (2H, br), 4.57 (2H, br), 6.54 (1H, s), 6.71 (1H, d, J=7.2 Hz), 7.15-7.20 (1H, m), 7.30 (1H, s), 7.37-7.40 (1H, m), 7.60-7.63 (1H, m), 8.16 (2H, br), 8.86 (2H, br). 
       Example 16 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(2-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}ethyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0811]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0812]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.50 (3H, s), 2.84 (2H, br), 3.14 (2H, br), 3.34 (3H, s), 3.25-3.45 (2H, m), 3.50-3.70 (1H, m), 3.90-4.08 (1H, m), 4.38 (2H, br), 4.47 (2H, br), 6.76 (1H, d, J=7.1 Hz), 6.93 (1H, s), 7.23 (1H, d, J=8.2 Hz), 7.36 (1H, s), 7.40 (1H, d, J=8.2 Hz), 7.69 (1H, br), 7.82 (1H, br), 7.90 (1H, d, J=2.1 Hz), 8.71 (2H, br). 
       Example 17 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0813]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0814]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.72 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.33 (3H, s), 2.40 (3H, s), 2.51 (3H, s), 2.89 (4H, br), 3.31 (3H, s), 3.50 (2H, br), 3.72-3.77 (1H, m), 4.02-4.07 (1H, m), 4.42 (2H, br), 4.61 (2H, br), 6.54 (1H, s), 6.70 (1H, br), 7.23 (1H, br), 7.34 (1H, s), 7.40 (1H, br), 7.64 (1H, br), 7.86 (1H, br), 8.73 (2H, br). 
       Example 18 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0815]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0816]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.71 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.33 (3H, s), 2.39 (3H, s), 2.51 (3H, s), 2.74 (2H, br), 3.15 (2H, br), 3.33 (3H, s), 3.51 (2H, br), 3.72-3.77 (1H, m), 4.02-4.07 (1H, m), 4.42 (2H, br), 4.75 (2H, br), 6.53 (1H, s), 6.70 (1H, br), 7.23-7.26 (1H, m), 7.36 (1H, s), 7.42-7.44 (1H, m), 7.64 (1H, br), 7.86 (1H, br), 8.76 (1H, br), 9.20 (1H, br). 
       Example 19 
     Synthesis of 7-aminomethyl-1,5-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0817]    10% Palladium on carbon (0.1 g) was added to an acetic acid solution (20 ml) of 1,5-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile (0.3 g), and catalytic reduction was carried out at room temperature under 4 atm. The catalyst was removed by celite filtration, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→5:5). The purified product was condensed under reduced pressure to give the title compound (0.17 g) as a yellowish white solid. 
         [0818]      1 H NMR (CDCl 3 ) δ ppm: 3.28 (1H, d, J=12.4 Hz), 3.42 (3H, s), 3.44 (3H, s), 3.38-3.42 (1H, m), 3.94 (2H, s), 7.26-7.29 (3H, m). 
       Example 20 
     Synthesis of 7-aminomethyl-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]dia zepine-2,4-dione 
       [0819]    The synthesis of the title compound was performed in the same manner as in Example 19 using appropriate starting materials. 
         [0820]      1 H-NMR (CDCl 3 ) δ ppm: 0.84 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.43 (3H, s), 3.75-3.82 (1H, m), 3.93 (2H, s), 4.13-4.19 (1H, m), 7.20-7.23 (1H, m), 7.25-7.27 (2H, m). 
       Example 21 
     Synthesis of 7-aminomethyl-1,3,3,5-tetramethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [0821]    The synthesis of the title compound was performed in the same manner as in Example 19 using appropriate starting materials. 
         [0822]      1 H NMR (CDCl 3 ) δ ppm: 0.85 (3H, s), 1.54 (3H, s), 3.42 (3H, s), 3.44 (3H, s), 3.93 (2H, s), 7.18-7.26 (3H, m). 
       Example 22 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[(pyridin-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0823]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0824]      1 H-NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.69-3.82 (1H, m), 3.84 (2H, s), 3.87 (2H, s), 4.04-4.20 (1H, m), 7.23-7.26 (3H, m), 7.29-7.32 (2H, m), 8.56-8.58 (2H, m). 
       Example 23 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0825]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0826]      1 H-NMR (CDCl 3 ) δ ppm: 0.84 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.56 (3H, s), 3.42 (3H, s), 3.77-3.88 (1H, m), 3.84 (2H, s), 3.88 (2H, s), 4.09-4.18 (1H, m), 7.11-7.15 (1H, m), 7.24-7.29 (3H, m), 7.63-7.65 (1H, m), 8.41-8.43 (1H, m). 
       Example 24 
     Synthesis of 1,5-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0827]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0828]      1 H NMR (CDCl 3 ) δ ppm: 2.59 (3H, s), 3.27 (1H, d, J=12.4 Hz), 3.37-3.43 (7H, m), 3.82 (2H, s), 3.86 (2H, s), 7.10-7.14 (1H, m), 7.23-7.26 (3H, m), 7.61-7.65 (1H, m), 8.39-8.42 (1H, m). 
       Example 25 
     Synthesis of 1,3,3,5-tetramethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0829]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0830]      1 H NMR (CDCl 3 ) δ ppm: 0.85 (3H, s), 1.54 (3H, s), 2.56 (3H, s), 3.43 (3H, s), 3.44 (3H, s), 3.82 (2H, s), 3.88 (2H, s), 7.11-7.15 (1H, m), 7.20-7.26 (3H, m), 7.62-7.64 (1H, m), 8.41-8.43 (1H, m). 
       Example 26 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[[[2-(pyridin-3-yl)ethyl]amino]methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0831]    Trimethyl orthoformate (9 ml) was added to a methanol solution (50 ml) of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (2.2 g) and 3-(2-aminoethyl)pyridine (1.0 g). The mixture was stirred at room temperature for 2 hours. 
         [0832]    The reaction liquid was condensed under reduced pressure, and a methanol solution (50 ml) of the residue was cooled with ice. Sodium borohydride (0.34 g) was added thereto, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction liquid, followed by concentration under reduced pressure. The residue was extracted by ethyl acetate. The organic layer was dried by anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=9:1). The purified product was condensed under reduced pressure to give the title compound (2.5 g) as a colorless oily matter. 
         [0833]      1 H NMR (CDCl 3 ) δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.80-2.90 (2H, m), 2.90-2.99 (2H, m), 3.39 (3H, s), 3.72-3.90 (1H, m), 3.83 (2H, s), 4.06-4.22 (1H, m), 7.14-7.20 (2H, m), 7.20-7.28 (2H, m), 7.54 (1H, td, J=2.0, 7.8 Hz), 8.45-8.53 (2H, m). 
       Example 27 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyrid in-5-yl)ethylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0834]    Sodium borohydride (0.15 g) was added to a methanol solution (150 ml) of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (1.1 g) and 5-(2-aminoethyl)-2-methyl-5H-furo[3,2-c]pyridin-4-one (1.0 g), and the mixture was stirred at room temperature overnight. The reaction liquid was filtered to remove insoluble matter, and the filtrate was condensed under reduced pressure. 
         [0835]    The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→5:5). The purified product was condensed under reduced pressure to give the title compound (1.1 g) as a colorless amorphous solid. 
         [0836]      1 H NMR (CDCl 3 ) δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.15 (1H, br), 2.42 (3H, s), 3.02-3.10 (2H, m), 3.36 (3H, s), 3.75-3.81 (1H, m), 3.86 (2H, s), 4.09-4.20 (3H, m), 6.49 (1H, d, J=6.7 Hz), 6.53 (1H, d, J=1.9 Hz), 7.15-7.21 (4H, m). 
       Example 28 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethylamino]methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0837]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [0838]      1 H-NMR (CDCl 3 ) δ ppm: 0.80 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.95 (2H, br), 3.36 (3H, s), 3.74-3.82 (1H, m), 3.86 (2H, br), 4.02-4.14 (1H, m), 4.20 (2H, br), 6.57 (1H, d, J=7.3 Hz), 6.96 (1H, d, J=2.0 Hz), 7.14-7.26 (4H, m), 7.50 (1H, d, J=2.0 Hz). 
       Example 29 
     Synthesis of 7,7′-azanediylbis(methylene)bis(1-ethyl-3,3,5-trimethyl-1H-benzo[b][1,4]diazepine-2,4-dione) 
       [0839]    10% Palladium on carbon (0.3 g) was added to an acetic acid solution (20 ml) of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile (1.4 g), and catalytic reduction was carried out at room temperature under 4 atm. The catalyst was removed by celite filtration, followed by concentration under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→5:5). The purified product was condensed under reduced pressure to give the title compound (0.19 g) as a colorless oily matter. 
         [0840]      1 H-NMR (CDCl 3 ) δ ppm: 0.84 (6H, s), 1.19 (6H, t, J=7.1 Hz), 1.54 (6H, s), 3.43 (6H, s), 3.71-3.92 (2H, m), 3.87 (4H, s), 4.01-4.18 (2H, m), 7.24-7.27 (6H, m). 
       Example 30 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridin-4-ylmethyl)amino}methyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione 
       [0841]    5-(2,2-Dihydroxyethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.21 g) and acetic acid (0.1 ml) were added to a 1,2-dichloroethane solution (15 ml) of 1-ethyl-3,3,5-trimethyl-7-{[(pyridin-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.38 g), and the mixture was stirred for 30 minutes at room temperature. Sodium triacetoxy borohydride (0.42 g) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→4:1). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether to give the title compound (0.47 g) as a white powder. 
       mp: 143 to 145° C. 
     Example 31 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0842]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 153 to 154° C. 
     Example 32 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0843]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 172 to 173° C. 
     Example 33 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[3-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl) propyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0844]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0845]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.66 (3H, s), 1.04 (3H, br), 1.33 (3H, s), 2.29 (2H, br), 2.41 (3H, s), 2.80 (3H, br). 3.08 (2H, br), 3.33 (3H, s), 3.73-3.79 (1H, m), 3.93-4.01 (3H, m), 4.46 (2H, br), 4.57 (2H, br), 6.56 (1H, s), 6.67 (1H, d, J=6.2 Hz), 7.42-7.44 (1H, m), 7.48-7.59 (2H, m), 7.88 (2H, br), 8.76 (1H, br), 8.93 (1H, br). 
       Example 34 
     Synthesis of 7,7′-(pyridin-4-ylmethylazanediyl)bis(methylene)bis(1-ethyl-3,3,5-trimethyl-1H-benzo[b][1,4]diazepine-2,4-dione)dihydrochloride 
       [0846]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0847]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.69 (6H, s), 1.07 (6H, t, J=7.1 Hz), 1.32 (6H, s), 3.35 (6H, s), 3.74-3.81 (2H, m), 3.94-4.04 (2H, m), 4.52 (2H, br), 4.82 (4H, s), 7.45-7.47 (4H, m), 8.08 (2H, d, J=6.7 Hz), 8.05-8.40 (2H, m), 8.88 (2H, d, J=6.7 Hz). 
       Example 35 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0848]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0849]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.67 (3H, s), 1.01 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.41-2.59 (5H, m), 2.83 (2H, br), 3.25 (3H, s), 3.61-3.83 (3H, m), 3.92-3.97 (1H, m), 4.16 (2H, br), 6.58 (1H, br), 7.22 (2H, br), 7.40 (2H, br), 7.48-7.63 (2H, m), 7.67-7.68 (1H, m), 7.71-7.75 (1H, m), 8.10-8.12 (1H, m), 8.24 (1H, br), 8.44 (1H, br). 
       Example 36 
     Synthesis of 1,5-dimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0850]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0851]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.38 (3H, s), 2.51 (3H, s), 2.54 (2H, br), 2.75 (2H, br), 3.05 (1H, d, J=12.4 Hz), 3.26 (6H, s), 3.32 (1H, d, J=12.4 Hz), 3.75 (2H, br), 4.14 (2H, br), 6.45 (1H, br), 6.63 (1H, br), 7.24 (1H, br), 7.33 (1H, br), 7.50 (2H, br), 7.68 (1H, br), 8.25 (1H, br), 8.56 (1H, br). 
       Example 37 
     Synthesis of 1,3,3,5-tetramethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0852]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0853]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.34 (3H, s), 2.51 (3H, s), 2.55 (2H, br), 2.82 (2H, br), 3.30 (6H, s), 3.78 (2H, br), 4.19 (2H, br), 6.73 (1H, br), 6.88 (1H, br), 7.31 (3H, br), 7.60 (2H, br), 7.91 (1H, d, J=2.0 Hz), 8.26 (1H, br), 8.56 (1H, br). 
       Example 38 
     Synthesis of 1,3,3,5-tetramethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0854]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0855]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.34 (3H, s), 2.41 (3H, s), 2.51 (3H, s), 2.56 (2H, br), 2.79 (2H, br), 3.30 (6H, s), 3.77 (2H, br), 4.15 (2H, br), 6.46 (1H, br), 6.63 (1H, br), 7.31 (3H, br), 7.50 (1H, br), 7.68 (1H, br), 8.24 (1H, br), 8.56 (1H, br). 
       Example 39 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)-N-(pyridin-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0856]    1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (0.92 g) and acetic acid (0.1 ml) were added to a 1,2-dichloroethane solution (15 ml) of (2-pyridine 3-ylethyl)pyridin-4-ylmethylamine (0.81 g), and the mixture was stirred for 30 minutes at room temperature. Sodium triacetoxyborohydride (0.90 g) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=100:0→90:10). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (1.0 ml) was added to an ethyl acetate solution (20 ml) of the residue, and the liquid was stirred at room temperature. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (0.83 g) as a white solid  1 H-NMR (DMSO-d 6 ) δ ppm: 0.68 (3H, s), 1.06 (3H, t, J=7.1 Hz), 1.33 (3H, s), 3.00 (2H, br), 3.32 (3H, s), 3.10-3.45 (4H, m), 3.74-3.79 (1H, m), 3.94-4.00 (3H, m), 7.43 (2H, br), 7.98-8.02 (2H, m), 8.45 (1H, d, J=8.0 Hz), 8.82-8.88 (6H, m). 
       Example 40 
     Synthesis of N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)benzamide hydrochloride 
       [0857]    Benzoyl chloride (0.13 ml) was added to an acetonitrile solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-[(2-pyridin-3-ylethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.38 g) and triethylamine (0.17 ml) under ice cooling. The mixture was stirred at room temperature overnight. An aqueous sodium hydrogencarbonate solution was added to the reaction mixture, followed by extraction by ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=91:9). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride ethanol solution (0.87 ml) was added to an isopropyl alcohol solution (10 ml) of the residue, and the liquid was condensed under reduced pressure. The residue was recrystallized from the ethanol-ether mixture to give the title compound (0.26 g) as a pale brown white powder. 
         [0858]      1 H NMR (DMSO-d 6 ) δ ppm: 0.73 (3H, bs), 0.98-1.14 (3H, m), 1.34 (3H, s), 2.74-3.94 (8H, m), 3.94-4.11 (1H, m), 4.52 and 4.82 (2H, bs), 6.90-7.60 (8H, m), 7.60-9.10 (4H, m). 
       Example 41 
     Synthesis of N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-4-methyl-N-(2-pyridin-3-ylethyl)benzamide hydrochloride 
       [0859]    The synthesis of the title compound was performed in the same manner as in Example 40 using appropriate starting materials. 
         [0860]      1 H NMR (DMSO-d 6 ) δ ppm: 0.73 (3H, s), 1.09 (3H, t, J=7.0 Hz), 1.34 (3H, s), 2.31 (3H, s), 2.88-3.94 (8H, m), 3.94-4.11 (1H, m), 4.35-5.05 (2H, m), 6.88-7.63 (7H, m), 7.63-9.10 (4H, m). 
       Example 42 
     Synthesis of N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide 
       [0861]    Triethylamine (0.15 ml) was added to a acetonitrile solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-[(2-pyridin-3-yl-ethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.35 g). The mixture was cooled with ice. Benzenesulphonyl chloride (0.13 ml) was added, and the mixture was stirred at room temperature overnight. The reaction liquid was condensed under reduced pressure. Water was added to the residue, followed by extraction by ethyl acetate. 
         [0862]    The organic layer was dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=30:70). The purified product was condensed under reduced pressure, and the residue was recrystallized from the ethyl acetate-ether mixture to give the title compound (0.1 g) as a white powder. 
       mp: 143.2 to 146.4° C. 
     Example 43 
     Synthesis of 7-{[N-benzyl-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [0863]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0864]      1 H NMR (DMSO-d 6 ) δ ppm: 0.72 (3H, s), 1.05 (3H, t, J=7.0 Hz), 1.34 (3H, s), 2.59-3.72 (8H, m), 3.72-3.94 (1H, m), 3.94-4.11 (1H, m), 4.33-4.65 (3H, m), 6.85-8.18 (10H, m), 8.30-8.77 (2H, m), 11.17 (1H, bs). 
       Example 44 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(4-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0865]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 160 to 161° C. 
     Example 45 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0866]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 171 to 174° C. 
     Example 46 
     Synthesis of 7-({N-(2,6-dimethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl]ethyl]amino}methyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0867]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 148 to 149° C. 
     Example 47 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(6-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0868]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 123 to 125° C. 
     Example 48 
     Synthesis of N-[2-({[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-7-yl)methyl][2-(pyridin-3-yl)ethyl]amino}methyl) phenyl]methanesulfonamide dihydrochloride 
       [0869]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0870]      1 H NMR (DMSO-d 6 ) δ ppm: 0.71 and 0.73 (3H, s), 0.90-1.20 (3H, m), 1.33 (3H, s), 2.69-2.80 (1H, bs), 2.85 (2H, bs), 2.92-3.10 (4H, m), 3.20-3.70 (3H, m), 3.70-3.96 (3H, m), 3.96-4.10 (1H, m), 4.46-4.73 (2H, m), 7.00-7.70 (7H, m), 7.70-8.30 (2H, m), 8.52-8.80 (2H, m), 9.30-9.59 (1H, m), 10.90 (1H, bs). 
       Example 49 
     Synthesis of 7-{[N-(2,4-dimethylthiazol-5-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0871]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0872]      1 H NMR (DMSO-d 6 ) δ ppm: 0.73 (3H, s), 1.09 (3H, t, J=7.0 Hz), 1.34 (3H, s), 2.30 (3H, bs), 2.59 (3H, s), 2.65-5.20 (13H, m), 6.32-8.07 (4H, m), 8.16-8.40 (1H, m), 8.66-8.90 (2H, m), 11.91 (1H, bs). 
       Example 50 
     Synthesis of N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-methyl-N-(2-pyridin-3-ylethyl)benzamide hydrochloride 
       [0873]    The synthesis of the title compound was performed in the same manner as in Example 40 using appropriate starting materials. 
         [0874]      1 H NMR (DMSO-d 6 ) δ ppm: 0.71 and 0.75 (3H, s), 1.00-1.12 (3H, m), 1.32 and 1.34 (3H, s), 2.03 and 2.04 (3H, s), 2.85-5.50 (8H, m), 3.26 and 3.34 (3H, s), 6.86 (0.4H, d, J=7.8 Hz), 7.05-7.98 (8.3H, m), 8.39 (0.9H, bs), 8.63 (0.4H, bs), 8.74 (0.5H, bs), 8.87 (0.5H, bs). 
       Example 51 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0875]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0876]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.72 (3H, s), 1.06 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.68 (3H, br), 3.10 (2H, br), 3.34 (3H, s), 3.18-3.60 (4H, m), 3.74-3.90 (3H, m), 3.99-4.05, (1H, m), 7.49 (2H, br), 7.73 (1H, br), 7.87 (1H, br), 7.98-8.01 (1H, br), 8.45 (1H, br), 8.68-8.70 (2H, m), 8.81 (1H, d, J=5.5 Hz), 8.89 (1H, br). 
       Example 52 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[(N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(thiazol-2-ylmethyl)amino]methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0877]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 171 to 172° C. 
     Example 53 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(thiazol-2-ylmethyl)amino}methyl)-1,5-dihydro benzo[b][1,4]diazepine-2,4-dione 
       [0878]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 146 to 147° C. 
     Example 54 
     Synthesis of 7-{[N-(2,6-dimethylpyridin-3-ylmethyl)-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione trihydrochloride 
       [0879]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0880]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.68 (3H, s), 1.02 (3H, t, J=7.1 Hz), 1.32 (3H, s), 3.32 (9H, s), 3.32 (3H, s), 3.67 (2H, br), 3.60-3.82 (1H, m), 3.78 (2H, br), 3.82 (2H, br), 3.97-4.04 (1H, m), 7.28 (1H, br), 7.34 (1H, br), 7.39-7.41 (1H, m), 7.67 (1H, d, J=7.8 Hz), 7.82-7.85 (1H, m), 8.43 (1H, br), 8.56 (1H, br), 8.61 (1H, br). 
       Example 55 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(4-m ethylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0881]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0882]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.67 (3H, s), 1.01 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.48 (3H, s), 2.70 (3H, s), 3.31 (3H, s), 3.63-3.75 (3H, m), 3.87 (4H, br), 3.95-4.08 (1H, m), 7.25 (1H, m), 7.34 (1H, m), 7.38-7.40 (1H, m), 7.81-7.86 (2H, m), 8.55 (1H, br), 8.62 (1H, d, J=5.2 Hz), 8.69 (1H, d, J=5.9 Hz), 8.86 (1H, br). 
       Example 56 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(4-methylpyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0883]    The synthesis of the title compound was performed in the same manner as in Example 39 using appropriate starting materials. 
         [0000]    White powder 
         [0884]      1 H NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.03 (3H, br), 1.33 (3H, s), 2.33 (3H, br), 2.86 (2H, br), 3.10 (2H, br), 3.32 (3H, s), 3.31-3.41 (1H, m), 3.77 (4H, br), 4.00-4.06 (1H, m), 7.20 (1H, br), 7.43 (2H, br), 7.80 (1H, br), 7.97 (1H, br), 8.41 (1H, br), 8.70 (2H, br), 8.79-8.81 (2H, m). 
       Example 57 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(4-methylthiazol-5-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0885]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 161 to 162° C. 
     Example 58 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0886]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 188 to 189° C. 
     Example 59 
     Synthesis of 2-methyl-2H-pyrazole-3-sulfonic acid 
       [0887]    N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)amide 
         [0888]    The synthesis of the title compound was performed in the same manner as in Example 42 using appropriate starting materials. 
         [0000]    White powder (ethyl acetate) 
       mp: 123 to 124° C. 
     Example 60 
     Synthesis of 7-{[N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]di azepine-2,4-dione dihydrochloride 
       [0889]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 136 to 145° C. 
     Example 61 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(2-pyridin-4-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0890]    The synthesis of the title compound was performed in the same manner as in Example 39 using appropriate starting materials. 
         [0891]      1 H NMR (DMSO-d 6 ) δ ppm: 0.71 (3H, s), 1.07 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.71 (5H, br), 3.20-3.39 (3H, m), 3.37 (3H, s), 3.55 (2H, br), 3.77 (2H, br), 3.99-4.04 (1H, m), 7.31 (1H, br), 7.47 (2H, br), 7.85 (2H, br), 7.95 (2H, br), 8.68 (1H, br), 8.85 (2H, br). 
       Example 62 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl) ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0892]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 164 to 165° C. 
     Example 63 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0893]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 181 to 183° C. 
     Example 64 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0894]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 134 to 136° C. 
     Example 65 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[(thiazol-2-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0895]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0896]      1 H NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.43 (3H, s), 3.74-3.84 (1H, m), 3.92 (2H, s), 4.09-4.18 (3H, m), 7.25-7.27 (3H, m), 7.30 (1H, d, J=3.3 Hz), 7.75 (1H, d, J=3.3 Hz). 
       Example 66 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0897]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0898]      1 H NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.38 (3H, s), 3.42 (3H, s), 3.74-3.84 (1H, m), 3.83 (2H, s), 3.87 (2H, s), 4.09-4.18 (1H, m), 7.09 (1H, d, J=4.9 Hz), 7.24-7.27 (3H, m), 8.39 (1H, d, J=4.9 Hz), 8.46 (1H, s). 
       Example 67 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[(4-methylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0899]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [0900]      1 H NMR (CDCl 3 ) δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.40 (3H, s), 3.43 (3H, s), 3.75-3.84 (1H, m), 3.86 (2H, s), 3.97 (2H, s), 4.09-4.18 (1H, m), 7.22-7.28 (3H, m), 8.65 (1H, s). 
       Example 68 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(4-methyl-7-oxo-7H-furo[2,3-c]pyridin-6-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0901]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 164-165° C. 
     Example 69 
     Synthesis of 7-{[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0902]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 193-195° C. 
     Example 70 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(4-methyl-7-oxo-7H-furo[2,3-c]pyridin-6-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0903]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 203-204° C. 
     Example 71 
     Synthesis of 7-{[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0904]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 181-182° C. 
     Example 72 
     Synthesis of 7-(1N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(thiazol-2-ylmethyl)amino]methyl)-1-ethyl-3,3,5-trimethyl-1,5-dih ydrobenzo[b][1,4]diazepine-2,4-dione 
       [0905]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 157-159° C. 
     Example 73 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(4-m ethylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0906]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0907]      1 H NMR (DMSO-d 6 ), δ ppm: 0.68 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.30 (3H, s), 2.70 (3H, s), 3.32 (3H, s), 3.68 (2H, s), 3.67-3.76 (1H, m), 3.84 (4H, br), 3.97-4.06 (1H, m), 7.25-7.27 (1H, m), 7.34 (1H, s), 7.43 (1H, d, J=8.4 Hz), 7.84 (1H, dd, J=6.0, 7.7 Hz), 8.48-8.50 (1H, m), 8.62 (1H, d, J=5.5 Hz), 8.95-8.97 (1H, m). 
       Example 74 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{(N-[(1-methyl-1H-indazol-3-yl)methyl]-N-[2-(pyridin-3-yl)ethyl]amino)methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0908]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0909]      1 H NMR (D 2 O), δ ppm: 0.73 (3H, s), 1.11 (3H, t, J=7.0 Hz), 1.41 (3H, s), 3.15-3.29 (2H, m), 3.30 (3H, s), 3.38-3.58 (2H, m), 3.68-3.88 (1H, m), 4.00-4.20 (1H, m), 4.04 (3H, s), 4.37 (2H, bs), 4.44 (2H, bs), 7.08-7.21 (1H, m), 7.35 (1H, d, J=7.8 Hz), 7.39-7.60 (5H, m), 7.65 (1H, dd, J=6.0, 7.5 Hz), 8.10 (1H, d, J=7.8 Hz), 8.35-8.49 (2H, m). 
       Example 75 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methyloxazol-4-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0910]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0911]      1 H NMR (D 2 O), δ ppm: 0.79 (3H, s), 1.14 (3H, t, J=7.0 Hz), 1.43 (3H, s), 2.48 (3H, s), 3.21-3.33 (2H, m), 3.37-3.52 (2H, m), 3.40 (3H, s), 3.77-3.93 (1H, m), 4.07-4.21 (1H, m), 4.36 (2H, s), 4.47 (2H, dd, J=13.6, 22.0 Hz), 7.50 (1H, dd, J=1.4, 8.4 Hz), 7.54-7.60 (1H, m), 7.63 (1H, d, J=8.4 Hz), 7.73 (1H, dd, J=5.6, 7.9 Hz), 7.95 (1H, bs), 8.09 (1H, d, J=7.9 Hz), 8.54 (1H, bs), 8.58 (1H, d, J=5.6 Hz). 
       Example 76 
     Synthesis of 7-{[N-[2-(2,3-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0912]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0913]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.33 (3H, s), 2.12 (3H, s), 2.31 (3H, s), 2.45 (3H, br), 2.77 (2H, br), 3.28 (3H, s), 3.71-3.83 (3H, m), 3.94-4.07 (3H, m), 4.08 (2H, br), 6.54 (1H, br), 7.24 (1H, br), 7.35 (2H, br), 7.42 (1H, br), 7.67 (1H, br), 8.26 (1H, br), 8.52 (1H, br). 
       Example 77 
     Synthesis of 7-{[N-[2-(2,3-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0914]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0915]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.33 (3H, s), 2.11 (3H, s), 2.24 (3H, br), 2.31 (3H, s), 2.80 (2H, br), 3.28 (3H, s), 3.71-3.84 (3H, m), 3.94-4.11 (5H, m), 6.50 (1H, br), 7.24 (1H, br), 7.36 (2H, br), 7.40 (1H, br), 7.59 (1H, br), 8.59 (1H, br), 8.64 (1H, br). 
       Example 78 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methylpyridin-3-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0916]    The synthesis of the title compound was performed in the same manner as in Example 39 using appropriate starting materials. 
         [0917]      1 H NMR (DMSO-d 6 ), δ ppm: 0.72 (3H, s), 1.05 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.70 (8H, br), 3.34 (3H, br), 3.78 (3H, br), 4.01-4.20 (5H, m), 7.47 (1H, br), 7.52 (1H, br), 7.85 (2H, br), 8.35 (2H, br), 8.65 (2H, br), 9.00 (1H, br). 
       Example 79 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(4-methylpyridin-3-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0918]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials.  1 H NMR (DMSO-d 6 ), δ ppm: 0.73 (3H, s), 1.06 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.43 (3H, s), 2.46 (3H, s), 3.36 (5H, br), 3.45 (2H, br), 3.77-3.88 (1H, m), 4.00-4.12 (1H, m), 4.45 (2H, br), 4.65 (2H, br), 7.52-7.54 (1H, m), 7.60 (1H, br), 7.88 (1H, d, J=6.0 Hz), 7.90 (1H, br), 7.71 (1H, d, J=6.0 Hz), 8.77 (1H, s), 9.15 (1H, s). 
       Example 80 
     Synthesis of 7-({N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(4-methylpyridin-3-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0919]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0920]      1 H NMR (DMSO-d 6 ), δ ppm: 0.73 (3H, s), 1.07 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.11 (3H, s), 2.45 (3H, s), 3.36 (5H, br), 3.50 (2H, br), 3.50-3.82 (4H, m), 3.95-4.08 (1H, m), 4.45 (2H, br), 4.53 (2H, br), 6.51 (1H, br), 7.56 (1H, br), 7.61 (1H, br), 7.87-7.89 (1H, m), 8.02 (1H, m), 8.71 (1H, d, J=5.8 Hz), 8.78 (1H, s). 
       Example 81 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methylpyridin-3-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0921]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials.  1 H NMR (DMSO-d 6 ), δ ppm: 0.74 (3H, s), 1.06 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.41 (3H, s), 2.65 (3H, s), 3.36 (7H, br), 3.70-3.79 (1H, m), 3.95-4.08 (1H, m), 4.47 (2H, br), 4.73 (2H, br), 7.54 (1H, br), 7.60 (1H, br), 7.87 (1H, dd, J=7.8, 5.7 Hz), 7.92 (1H, br), 8.33 (1H, d, J=7.8 Hz), 8.66 (1H, d, J=5.7 Hz), 9.12 (1H, s). 
       Example 82 
     Synthesis of 7-({N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(2-methylpyridin-3-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0922]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0923]      1 H NMR (DMSO-d 6 ), δ ppm: 0.75 (3H, s), 1.07 (3H, t, J=7.1 Hz), 1.35 (3H, s), 2.12 (3H, s), 2.67 (3H, s), 3.36 (5H, br), 3.43 (2H, br), 3.70-3.90 (4H, m), 4.00-4.08 (1H, m), 4.45 (2H, br), 4.50 (2H, br), 6.50 (1H, br), 7.55-7.57 (1H, m), 7.61 (1H, br), 7.85-7.88 (1H, m), 7.94 (1H, br), 8.36 (1H, br), 8.67 (1H, d, J=5.6 Hz). 
       Example 83 
     Synthesis of 7-({N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4 H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0924]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 152-153° C. 
     Example 84 
     Synthesis of 1-ethyl-7-({N-(4-methoxypyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0925]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0926]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.14 (3H, t, J=7.1 Hz), 1.50 (3H, s), 2.43 (3H, s), 2.77-2.87 (2H, m), 3.29 (3H, s), 3.61 (1H, d, J=14.3 Hz), 3.68-3.74 (2H, m), 3.78 (1H, d, J=14.3 Hz), 3.86 (3H, s), 3.97-4.08 (1H, m), 4.09-4.19 (3H, m), 6.43-6.46 (2H, m), 6.78 (1H, d, J=5.8 Hz), 7.00 (2H, br), 7.05 (1H, s), 7.10 (1H, d, J=7.3 Hz), 8.39-8.40 (2H, m). 
       Example 85 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]py ridin-5-yl)ethyl]-N-(4-trifluoromethylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0927]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 162-164° C. 
     Example 86 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(4-methylthiazol-5-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0928]    1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (0.423 g) and acetic acid (0.14 g) were added to a 1,2-dichloroethane solution (10 ml) of N-(4-methylthiazol-5-ylmethyl)-N-(2-pyridin-3-ylethyl)amine (0.36 g). The mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.48 g) was added, and the mixture was stirred at room temperature overnight. The reaction liquid was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=100:0→50:50). The purified product was condensed under reduced pressure. The residue was washed with diethyl ether, and dried to give the title compound (0.37 g) as a white powder. 
       mp: 118-120° C. 
     Example 87 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(5-trifluoromethylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0929]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 138-140° C. 
     Example 88 
     Synthesis of 1-ethyl-7-({N-(5-fluoropyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4 H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0930]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 144-146° C. 
     Example 89 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-methylpyridin-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0931]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 153-154° C. 
     Example 90 
     Synthesis of 1-Ethyl-7-({N-(3-fluoropyridin-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4 H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0932]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diethyl ether) 
       mp: 149-151° C. 
     Example 91 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-methyl-2H-pyrazol-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [0933]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0934]      1 H NMR (D 2 O), δ ppm: 0.79 (3H, s), 1.11 (3H, t, J=7.0 Hz), 1.43 (3H, s), 3.09-3.70 (5H, m), 3.39 (3H, s), 3.45 (2H, s), 3.70-3.94 (1H, m), 3.94-4.59 (5H, m), 6.3-6.57 (1H, m), 7.30-7.65 (4H, m), 7.82-8.06 (1H, m), 8.15-8.47 (1H, m), 8.51 (1H, bs), 8.54-8.74 (1H, m). 
       Example 92 
     Synthesis of 1-ethyl-7-{[N-(1H-indol-7-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0935]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    White powder (ethanol) 
       mp: 155-167.8° C. 
     Example 93 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[2-(4-methylpyridin-3-yl)ethylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0936]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [0937]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.32 (3H, s), 2.94-2.96 (2H, m), 3.00 (2H, br), 3.42 (3H, s), 3.74-3.74 (1H, m), 3.96 (2H, br), 4.04-4.11 (1H, m), 7.07 (1H, d, J=4.9 Hz), 7.26-7.28 (2H, m), 7.34 (1H, br), 8.33 (1H, d, J=4.9 Hz), 8.38 (1H, s). 
       Example 94 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[2-(2-methylpyridin-3-yl)ethylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0938]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [0939]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.55 (3H, s), 2.85-2.93 (4H, m), 3.41 (3H, s), 3.75-3.83 (1H, m), 3.86 (2H, s), 4.11-4.17 (1H, m), 7.08 (1H, dd, J=7.6, 4.8 Hz), 7.19-7.21 (2H, m), 7.24-7.26 (1H, m), 7.44 (1H, dd, J=7.6, 1.6 Hz), 8.37 (1H, dd, 4.8, 1.6 Hz). 
       Example 95 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(2-methyloxazol-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0940]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0941]      1 H NMR (DMSO-d 6 ), δ ppm: 0.69 (3H, s), 1.06 (3H, t, J=7.1 Hz), 1.33 (3H, s), 2.395 (3H, s), 2.404 (3H, s), 3.32 (3H, s), 3.47 (2H, br), 3.74-3.81 (1H, m), 3.95-4.06 (1H, m), 4.23 (2H, br), 4.37 (4H, br), 6.55 (1H, s), 6.76 (1H, d, J=7.4 Hz), 7.48 (2H, br), 7.57 (1H, d, J=7.4 Hz), 7.67 (1H, br), 8.14 (1H, br). 
       Example 96 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(oxazol-5-ylmethyl)amino}methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0942]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0943]      1 H NMR (DMSO-d 6 ), δ ppm: 0.66 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.39 (3H, s), 3.21 (3H, s), 3.28-3.49 (2H, m), 3.74 (1H, br), 3.91-3.97 (1H, m), 4.20 (6H, br), 6.69 (1H, s), 6.69-6.71 (1H, m), 7.11-7.31 (4H, m), 7.54 (1H, d, J=7.5 Hz), 8.33 (1H, br). 
       Example 97 
     Synthesis of 7-({N-(2,4-dimethylthiazol-5-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0944]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    Pale yellow powder 
       mp: 187-188° C. 
     Example 98 
     Synthesis of 7-{[N-(2-chloropyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0945]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
       mp: 183-187° C. 
     Example 99 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)-N-(quinolin-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0946]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
       mp: 136-141° C. 
     Example 100 
     Synthesis of 7-{[N-[2-(2,6-dimethylpyridin-3-yl)ethyl]-N-(4-methylthiazol-5-yl methyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0947]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 136-137° C. 
     Example 101 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0948]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 139-140° C. 
     Example 102 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(4-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0949]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 145-147° C. 
     Example 103 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(4-methylpyridin-3-ylmethyl)-N-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}methyl)-1,5-dihydr obenzo[b][1,4]diazepine-2,4-dione 
       [0950]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 138-142° C. 
     Example 104 
     Synthesis of 7-{[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0951]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 144-145° C. 
     Example 105 
     Synthesis of 7-{[N-[2-(2,3-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0952]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 148-150° C. 
     Example 106 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0953]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 125-127° C. 
     Example 107 
     Synthesis of 7-({N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4 H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0954]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 193-195° C. 
     Example 108 
     Synthesis of 7-({N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-[2-(2,6-dimethylpyridin-3-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0955]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
         [0956]      1 H NMR (DMSO-d 6 ), δ ppm: 0.75 (3H, s), 1.07 (3H, t, J=7.1 Hz), 1.35 (3H, s), 2.11 (3H, s), 2.65 (3H, br), 2.71 (3H, br), 3.36 (5H, br), 3.50 (3H, s), 3.60-3.82 (3H, m), 4.00-4.10 (1H, m), 4.44 (2H, br), 4.53 (2H, br), 6.50 (1H, br), 7.57-7.67 (2H, m), 7.69 (1H, d, J=7.9 Hz), 8.00 (1H, br), 8.23 (1H, br). 
         [0957]    The following compounds shown in Examples 109 to 308 can be prepared by the same manner as mentioned above or a conventional manner using appropriate starting materials. 
       Example 109 
     1-Ethyl-3,3,5-trimethyl-7-{[oxazol-5-ylmethyl-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 110 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-thiazol-2-ylmethyl-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 111 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-thiazol-5-ylmethyl-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 112 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-thiazol-4-ylmethyl-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 113 
     1-Ethyl-3,3,5-trimethyl-7-{[(4-methyl-thiazol-2-ylmethyl)-(2-pyri din-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 114 
     7-{[(4,5-Dimethyl-thiazol-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 115 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-methyl-pyridin-4-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 116 
     1-Ethyl-7-{[(3-fluoro-pyridin-4-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 117 
     1-Ethyl-3,3,5-trimethyl-7-{[(3-methyl-pyridin-4-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 118 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-methyl-pyridin-3-ylmethyl)-(2-pyri din-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 119 
     7-{[[2-(2,6-Dimethyl-pyridin-3-yl)-ethyl]-(2-methyl-pyridin-3-ylm ethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 120 
     1-Ethyl-3,3,5-trimethyl-7-{[(3-methyl-pyridin-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 121 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-(4-trifluoromethyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 122 
     1-Ethyl-7-{[(2-methoxy-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 123 
     7-{[(2,6-Dimethyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 124 
     1-Ethyl-7-{[(3-hydroxy-benzyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 125 
     1-Ethyl-7-{[furan-2-ylmethyl-(2-pyridin-3-yl-ethyl)-amino]-methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 126 
     1-Ethyl-7-{[furan-3-ylmethyl-(2-pyridin-3-yl-ethyl)-amino]-methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 127 
     1-Ethyl-3,3,5-trimethyl-7-{[(5-methyl-furan-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 128 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-methyl-furan-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 129 
     7-{[(4,5-Dimethyl-furan-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 130 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-(5-trifluoromethyl-furan-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 131 
     1-Ethyl-3,3,5-trimethyl-7-{[(3-methyl-thiophen-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 132 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-pyridin-3-yl-ethyl)-thiophen-2-ylmethyl-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 133 
     7-{[(4,5-Dimethyl-thiophen-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-ami no]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diaz epine-2,4-dione 
     Example 134 
     1-Ethyl-3,3,5-trimethyl-7-{2-[(4-methyl-thiazol-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 135 
     1-Ethyl-3,3,5-trimethyl-7-{2-[(4-methyl-thiazol-5-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 136 
     1-Ethyl-3,3,5-trimethyl-7-[(2-[(2-methyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 137 
     1-Ethyl-3,3,5-trimethyl-7-[2-[(4-methyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 138 
     1-Ethyl-3,3,5-trimethyl-7-[(2-[(3-methyl-pyridin-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 139 
     7-{2-[(2,6-Dimethyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diaz epine-2,4-dione 
     Example 140 
     N-(2-{[[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-ethyl]-(2-pyridin-3-yl-ethyl)-amino]-methyl}-phenyl)-methanesulfonamide 
     Example 141 
     7-{2-[(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 142 
     1-Ethyl-3,3,5-trimethyl-7-{3-[(4-methyl-thiazol-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 143 
     1-Ethyl-3,3,5-trimethyl-7-[3-[(4-methyl-thiazol-5-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 144 
     1-Ethyl-3,3,5-trimethyl-7-{3-[(2-methyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 145 
     1-Ethyl-3,3,5-trimethyl-7-{3-[(4-methyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 146 
     1-Ethyl-3,3,5-trimethyl-7-{3-[(3-methyl-pyridin-2-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 147 
     N-(2-{[[3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-propyl]-(2-pyridin-3-yl-ethyl)-amino]-methyl}-phenyl)-methanesulfonamide 
     Example 148 
     7-{3-[(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 149 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-pyridin-3-ylmethyl)-[2-(7-oxo-7H-furo[2,3-c]pyridin-6-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 150 
     1-Ethyl-3,3,5-trimethyl-7-({oxazol-5-ylmethyl-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4 ]diazepine-2,4-dione 
     Example 151 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiazol-2-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 152 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiazol-4-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 153 
     1-Ethyl-3,3,5-trimethyl-7-({(4-methyl-thiazol-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 154 
     7-({(4,5-Dimethyl-thiazol-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 155 
     7-({(2,4-Dimethyl-thiazol-5-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 156 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-pyridin-4-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 157 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-pyridin-4-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 158 
     1-Ethyl-7-({(3-fluoro-pyridin-4-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 159 
     1-Ethyl-3,3,5-trimethyl-7-({(3-methyl-pyridin-4-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 160 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-pyridin-3-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 161 
     1-Ethyl-3,3,5-trimethyl-7-({(3-methyl-pyridin-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 162 
     1-Ethyl-3,3,5-trimethyl-7-{[[ 2 -(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-trifluoromethyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 163 
     1-Ethyl-7-({(2-methoxy-pyridin-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 164 
     7-({(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 165 
     N-[2-({(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 166 
     1-Ethyl-7-({(3-hydroxy-benzyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 167 
     1-Ethyl-7-({furan-2-ylmethyl-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 168 
     1-Ethyl-7-({furan-3-ylmethyl-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 169 
     1-Ethyl-3,3,5-trimethyl-7-({(5-methyl-furan-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 170 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-furan-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 171 
     7-({(4,5-Dimethyl-furan-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 172 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(5-trifluoromethyl-furan-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 173 
     7-({(4,5-Dimethyl-thiophen-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 174 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiophen-2-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 175 
     1-Ethyl-3,3,5-trimethyl-7-({(3-methyl-thiophen-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 176 
     7-({(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 177 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyri din-5-yl)-ethyl]-oxazol-4-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 178 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiazol-5-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 179 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiazol-4-ylmethyl-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 180 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyri din-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 181 
     7-({(4,5-Dimethyl-thiazol-2-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 182 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyri din-5-yl)-ethyl]-(2-methyl-pyridin-4-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 183 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-pyridin-3-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 184 
     1-Ethyl-3,3,5-trimethyl-7-{[[ 2 -(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 185 
     1-Ethyl-7-({(2-methoxy-pyridin-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 186 
     N-[2-({(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 187 
     1-Ethyl-7-({(3-hydroxy-benzyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 188 
     1-Ethyl-7-({furan-2-ylmethyl-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 189 
     1-Ethyl-7-({furan-3-ylmethyl-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 190 
     1-Ethyl-3,3,5-trimethyl-7-({(5-methyl-furan-2-ylmethyl)-[2-(2-met hyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 191 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-furan-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 192 
     7-({(4,5-Dimethyl-furan-2-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 193 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(5-trifluoromethyl-furan-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 194 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-thiophen-2-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 195 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-thiophen-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 196 
     7-({(4,5-Dimethyl-thiophen-2-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 197 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 198 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 199 
     N-[2-({(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 200 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(3-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 201 
     7-{[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 202 
     7-{[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 203 
     7-{[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 204 
     N-(2-{[[ 2 -(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-amino]-methyl}-phenyl)-methanesulfonamide 
     Example 205 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(4-methyl-thiazol-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 206 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(4-methyl-thiazol-5-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 207 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(4-methyl-pyridin-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 208 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(3-methyl-pyridin-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 209 
     N-[2-({[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-ethyl]-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 210 
     7-(2-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 211 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 212 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 213 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 214 
     7-(2-{(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 215 
     N-[2-({[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-ethyl]-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 216 
     7-(2-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 217 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 218 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 219 
     1-Ethyl-3,3,5-trimethyl-7-{2-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 220 
     1-Ethyl-3,3,5-trimethyl-7-{(2-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 221 
     1-Ethyl-3,3,5-trimethyl-7-[(2-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-ethyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 222 
     N-[2-({[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-ethyl]-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 223 
     7-(2-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 224 
     7-{2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 225 
     7-{2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 226 
     7-{2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 227 
     7-[2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-ethyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 228 
     7-{2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 229 
     N-[2-({[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-[2-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 230 
     7-{2-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-amino]-ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 231 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(4-methyl-thiazol-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 232 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(4-methyl-thiazol-5-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 233 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(2-methyl-pyridin-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 234 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(4-methyl-pyridin-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 235 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(3-methyl-pyridin-2-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 236 
     N-[2-({[3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-propyl]-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 237 
     7-(3-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 238 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 239 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 240 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 241 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 242 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 243 
     7-{3-[(2,6-Dimethyl-pyridin-3-ylmethyl)-(2-pyridin-3-yl-ethyl)-amino}-propyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 244 
     7-(3-{(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 245 
     N-[2-({[3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-propyl]-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 246 
     7-(3-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trim ethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 247 
     1-Ethyl-3,3,5-trimethyl-7-[3-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 248 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 249 
     1-Ethyl-3,3,5-trimethyl-7-[3-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 250 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 251 
     1-Ethyl-3,3,5-trimethyl-7-{3-[[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-propyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 252 
     N-[2-({[3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-yl)-propyl]-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 253 
     7-(3-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trim ethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 254 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-2-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 255 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-thiazol-5-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 256 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 257 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 258 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(3-methyl-pyridin-2-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 259 
     N-[2-({[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)-propyl]-amino}-methyl)-phenyl]-methane sulfonamide 
     Example 260 
     7-{3-[[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-amino]-propyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 261 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(2-methyl-pyridin-3-ylmethyl)-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 262 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(4-methyl-7-oxo-7H-thieno[2,3-c]pyridin-6-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 263 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(4-methyl-7-oxo-7H-thieno[2,3-c]pyridin-6-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 264 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(2-methyl-pyridin-3-ylmethyl)-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 265 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(7-methyl-4-oxo-4H-thieno[3,2-c]pyridin-5-yl)-ethyl]-(2-methyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 266 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(7-methyl-4-oxo-4H-thieno[3,2-c]pyridin-5-yl)-ethyl]-(4-methyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 267 
     1-Ethyl-3,3,5-trimethyl-7-({oxazol-5-ylmethyl-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 268 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-thiazol-2-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 269 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-thiazol-5-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 270 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-thiazol-4-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 271 
     1-Ethyl-3,3,5-trimethyl-7-({(4-methyl-thiazol-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 272 
     1-Ethyl-3,3,5-trimethyl-7-({(4-methyl-thiazol-5-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 273 
     7-({(4,5-Dimethyl-thiazol-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 274 
     7-({(2,4-Dimethyl-thiazol-5-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 275 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-pyridin-4-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 276 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-pyridin-4-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 277 
     1-Ethyl-7-({(3-fluoro-pyridin-4-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 278 
     1-Ethyl-3,3,5-trimethyl-7-({(3-methyl-pyridin-4-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 279 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-pyridin-3-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 280 
     1-Ethyl-3,3,5-trimethyl-7-({(4-methyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b ][1,4]diazepine-2,4-dione 
     Example 281 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-(4-trifluoromethyl-pyridin-3-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 282 
     1-Ethyl-7-({(2-methoxy-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinol in-2-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 283 
     7-({(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 284 
     N-[2-({(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-b enzo[b][1,4]diazepin-7-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-phenyl]-methanesulfonamide 
     Example 285 
     1-Ethyl-7-({(3-hydroxybenzyl)-[2-(1-oxo-2H-isoquinolin-2-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 286 
     1-Ethyl-7-({furan-2-ylmethyl-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 287 
     1-Ethyl-7-({furan-3-ylmethyl-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 288 
     1-Ethyl-3,3,5-trimethyl-7-({(5-methyl-furan-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 289 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-furan-3-ylmethyl)-[2-(2-oxo-3,4-divinyl-2H-pyridin-1-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 290 
     7-({(4,5-Dimethyl-furan-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo [b][1,4]diazepine-2,4-dione 
     Example 291 
     1-Ethyl-3,3,5-trimethyl-7-{[[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-(5-trifluoromethyl-furan-2-ylmethyl)-amino]-methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 292 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-thiophen-2-ylmethyl-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diaz epine-2,4-dione 
     Example 293 
     1-Ethyl-3,3,5-trimethyl-7-({(3-methyl-thiophen-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 294 
     7-({(4,5-Dimethyl-thiophen-2-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 295 
     7-({(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 296 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(4-methyl-thiazol-5-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 297 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(4-methyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 298 
     1-Ethyl-3,3,5-trimethyl-7-(2-{(2-methyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-ethyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 299 
     7-(2-{(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 300 
     7-(2-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(1-oxo-2H-isoquinol in-2-yl)-ethyl]-amino}-ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 301 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(4-methyl-thiazol-5-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 302 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(4-methyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 303 
     1-Ethyl-3,3,5-trimethyl-7-(3-{(2-methyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 304 
     7-(3-{(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(1-oxo-2H-isoquinolin-2-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 305 
     7-(3-{(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-[2-(1-oxo-2H-isoquinol in-2-yl)-ethyl]-amino}-propyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 306 
     1-Ethyl-3,3,5-trimethyl-7-({(2-methyl-pyridin-3-ylmethyl)-[2-(2-oxo-2H-quinolin-1-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 307 
     1-Ethyl-3,3,5-trimethyl-7-({(4-methyl-pyridin-3-ylmethyl)-[2-(2-oxo-2H-quinolin-1-yl)-ethyl]-amino}-methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 308 
     7-({(2,6-Dimethyl-pyridin-3-ylmethyl)-[2-(2-oxo-2H-quinolin-1-yl)-ethyl]-amino}-methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 309 
     7-{[N-(4-Chloropyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]m ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [0958]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
       mp: 200-205° C. (dec.) 
     Example 310 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0959]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 161-165° C. 
     Example 311 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0960]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 144-146° C. 
     Example 312 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0961]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 127-128° C. 
     Example 313 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4 H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-tri methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0962]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 197-199° C. 
     Example 314 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(4-methyl-7-oxo-7 H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-tri methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0963]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 190-193° C. 
     Example 315 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(4-methylthiazol-2-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0964]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white amorphous 
         [0965]      1 H NMR (D 2 O), δ ppm: 0.75 (3H, s), 1.10 (3H, t, J=7.2 Hz), 1.42 (3H, s), 2.39 (3H, s), 3.25-3.36 (4H, m), 3.37 (3H, s), 3.73-3.87 (1H, m), 4.07-4.22 (3H, m), 4.41 (2H, s), 7.18 (1H, d, J=1.0 Hz), 7.32-7.38 (1H, m), 7.38-7.43 (1H, m), 7.49 (1H, d, J=8.3 Hz), 7.99 (1H, dd, J=6.0, 8.0 Hz), 8.44 (1H, d, J=8.3 Hz), 8.66-8.73 (2H, m) 
       Example 316 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0966]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 123-125° C. 
     Example 317 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0967]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 127-129° C. 
     Example 318 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0968]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 104-111° C. 
     Example 319 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0969]    4 M HCl/AcOEt (90 μl) was added to an ethyl acetate solution (1 ml) of 1-ethyl-7-({(2-methoxymethylpyridin-3-ylmethyl)-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (26 mg) and stirred for 5 minutes at room temperature. The resulting precipitate was collected and washed with ether to give the title compound as a white powder (14 mg). 
         [0970]      1 H NMR (DMSO-d 6 ), δ ppm: 0.75 (3H, s), 1.05 (3H, t, J=7.1 Hz), 1.35 (3H, s), 2.16 (3H, s), 3.27-3.33 (8H, m), 3.70-4.40 (6H, m), 4.52 (2H, br), 4.65 (2H, br), 6.93 (1H, s), 7.28-7.48 (4H, m), 7.72-7.84 (1H, m), 7.97 (1H, s), 8.35 (1H, br), 8.53-8.65 (1H, m). 
       Example 320 
     1-Ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-2-trifluoromethyl-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0971]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 132-134° C. 
     Example 321 
     1-Ethyl-3,3,5-trimethyl-7-({N-(3-methyl-3H-imidazol-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0972]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 106-108° C. 
     Example 322 
     1-Ethyl-3,3,5-trimethyl-7-({N-(3-methyl-3H-imidazol-4-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0973]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 100-105° C. 
     Example 323 
     1-Ethyl-7-({N-[2-(2-methoxymethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0974]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 123-126° C. 
     Example 324 
     1-Ethyl-7-({N-[2-(2-methoxymethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0975]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    pale yellow powder 
         [0976]      1 H NMR (DMSO-d 6 ), δ ppm: 0.69 (3H, s), 1.01 (3H, t, J=7.1 HZ), 1.33 (3H, s), 2.22 (3H, s), 2.80 (2H, s), 3.27 (3H, s), 3.30 (3H, s), 3.61-4.05 (6H, m), 4.12 (2H, br), 4.48 (2H, s), 6.63 (1H, d, J=7.4 Hz), 6.78 (1H, s), 7.22 (1H, br), 7.32-7.33 (2H, m), 7.54 (1H, d, J=7.0 Hz), 7.61 (1H, d, J=5.7 Hz), 8.61 (1H, d, J=5.7 Hz), 8.63 (1H, s). 
       Example 325 
     7-({N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(2-methoxymethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [0977]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    ivory powder 
         [0978]      1 H NMR (DMSO-d 6 ), δ ppm: 0.69 (3H, s), 1.03 (3H, t, J=7.1 Hz), 1.32 (3H, s), 2.04 (3H, s), 2.71 (2H, br), 3.27 (3H, s), 3.30 (3H, br), 3.45-4.00 (6H, m), 3.85 (3H, s), 4.39-4.63 (4H, m), 6.44 (1H, br), 6.61-7.02 (2H, m), 7.05-7.95 (4H, m). 
       Example 326 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-phenyl-N-(2-pyridin-3-ylethyl)acetamide hydrochloride 
       [0979]    The synthesis of the title compound was performed in the same manner as in Example 40 using appropriate starting materials. 
         [0000]    white amorphous 
         [0980]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 and 0.73 (3H, s), 0.95-1.13 (3H, m), 1.32 and 1.33 (3H, s), 2.91-3.03 (2H, m), 3.22 and 3.25 (3H, s), 3.50-3.82 (5H, m), 3.96-4.09 (1H, m), 4.56-4.74 (2H, m), 7.04-7.34 (7H, m), 7.42-7.52 (1H, m), 7.78 (1H, bs), 8.19 (1H, bs), 8.65-8.77 (2H, m) 
       Example 327 
     N-[2-({N′-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-ylmethyl)-N′-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)phenyl]methanesulfonamide 
       [0981]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 161-163° C. 
     Example 328 
     7-({N-(2-Chloropyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0982]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 158.7-160.8° C. 
     Example 329 
     3-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbonitrile 
       [0983]    2-Chloro-3-({(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-[2-(2-methyl-4-oxo-4-H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine (0.3 g), zinc cyanide (120 mg), tris(dibenzylideneacetone)dipalladium (24 mg), 1,1′-bis(diphenylphosphino)ferrocene (14 mg), and zinc powder (3.4 mg) were added to DMF (3 ml), and the mixture was heated at 95° C. for 3 hours. The reaction liquid was cooled to room temperature. Water was added to the reaction mixture and subjected to celite filtration. Extraction with ethyl acetate was performed. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=93:7). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether to give the title compound (1.35 g) as a white powder. 
       mp: 113.5-117.5° C. 
     Example 330 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-(2-pyrid in-3-ylethyl)acetamide hydrochloride 
       [0984]    To a solution of 1-ethyl-3,3,5-trimethyl-7-[(2-pyridine 3-ylethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.5 g), 1-methyl-3-indoleacetic acid (0.27 g), and 1-hydroxybenzotriazole (HOBT) (0.24 g) in acetonitrile (10 ml), N-(3-dimethylaminopropyl)-NT-ethylcarbodiimide hydrochloride (WSC) (0.30 g) was added and stirred at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure. Ethyl acetate and water were added to the residue and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=1:3→0:1). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (1.1 ml) was added to a 2-propanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.26 g) as a pale orange white amorphous. 
         [0985]      1 H NMR (DMSO-d 6 ), δ ppm: 0.65 and 0.69 (3H, s), 0.95-1.13 (3H, m), 1.31 and 1.32 (3H, s), 2.90-3.05 (2H, m), 3.06 and 3.14 (3H, s), 3.20-3.90 (5H, m), 3.70 and 3.73 (3H, s), 3.90-4.08 (1H, m), 4.55-4.79 (2H, m), 6.96 (1H, t, J=7.4 Hz), 7.05-7.24 (4H, m), 7.32-7.42 (2H, m), 7.43-7.55 (1H, m), 7.63-7.79 (1H, m), 8.13 (1H, bs), 8.57-8.72 (2H, m) 
       Example 331 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(1-pyridin-3-ylethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0986]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 128-132° C. 
     Example 332 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-phenyl-N-(2-pyridin-3-ylethyl)isobutyramide hydrochloride 
       [0987]    To a solution of 1-ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.5 g), 2-Phenylisobutyric acid (0.24 g), and diisopropylethylamine (0.23 ml) in DMF (10 ml), 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (0.50 g) was added and stirred at 40° C. for 10 hours. Water was added to the reaction mixture, and stirred for 1 hour, and, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=1:1). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution was added to a 2-propanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.35 g) as a white amorphous. 
         [0988]      1 H NMR (DMSO-d 6 ), δ ppm: 0.67 and 0.72 (3H, s), 0.90-1.20 (3H, m), 1.20-1.40 (3H, m), 1.43 and 1.48 (6H, s), 2.30-2.50 (1H, m), 2.83-3.40 (5H, m), 3.40-4.30 (4H, m), 4.57-4.79 (1H, m), 6.76-7.03 (1H, m), 7.03-7.56 (8H, m), 7.56-8.80 (3H, m) 
       Example 333 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-3-phenyl-N-(2-pyridin-3-ylethyl)propionamide hydrochloride 
       [0989]    The synthesis of the title compound was performed in the same manner as in Example 40 using appropriate starting materials. 
         [0000]    white amorphous 
         [0990]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 and 0.72 (3H, s), 0.95-1.12 (3H, m), 1.33 (3H, s), 2.53-2.69 (2H, m), 2.69-2.86 (2H, m), 2.90-3.03 (2H, m), 3.25 and 3.28 (3H, s), 3.45-3.68 (2H, m), 3.69-3.81 (1H, m), 3.96-4.10 (1H, m), 4.53-4.69 (2H, m), 7.04-7.29 (7H, m), 7.43 and 7.45 (1H, d, J=4.9 Hz), 7.78-7.86 (1H, m), 8.10-8.27 (1H, m), 8.57-8.77 (2H, m) 
       Example 334 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)-2-quinolin-6-ylacetamide dihydrochloride 
       [0991]    The synthesis of the title compound was performed in the same manner as in Example 332 using appropriate starting materials. 
         [0000]    white amorphous 
         [0992]      1 H NMR (DMSO-d 6 ), δ ppm: 0.68 and 0.70 (3H, s), 1.00-1.08 (3H, m), 1.31 and 1.32 (3H, s), 3.03 (1H, t, J=7.0 Hz), 3.10-3.18 (1H, m), 3.23 and 3.26 (3H, s), 3.40-3.90 (2H, m), 3.95-4.13 (4H, m), 4.60-4.88 (2H, m), 7.18-7.29 (2H, m), 7.42-7.52 (1H, m), 7.66-8.04 (4H, m), 8.07-8.21 (1H, m), 8.28-8.45 (1H, m), 8.65-8.93 (3H, m), 9.06-9.16 (1H, m) 
       Example 335 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride 
       [0993]    The synthesis of the title compound was performed in the same manner as in Example 332 using appropriate starting materials. 
         [0000]    white powder 
         [0994]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 and 0.76 (3H, s), 1.00-1.13 (3H, m), 1.33 and 1.34 (3H, s), 2.98 (1H, t, J=7.2 Hz), 3.10-3.17 (1H, m), 3.29 and 3.33 (3H, s), 3.50-3.68 (1H, m), 3.68-3.84 (2H, m), 3.97-4.13 (1H, m), 4.55-4.72 (2H, m), 4.76-4.87 (2H, m), 6.63-7.05 (4H, m), 7.15-7.38 (2H, m) 7.41-7.60 (1H, m), 7.75-7.88 (1H, m), 8.17-8.38 (1H, m), 8.56-8.86 (2H, m), 10.84 and 10.89 (1H, s) 
       Example 336 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]N-(pyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [0995]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 124-127° C. 
     Example 337 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(3-methyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride 
       [0996]    N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-oxo-2,3-dihydrobenzoimidazol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride (0.26 g), cesium carbonate (0.43 g), and methyl iodide (0.04 ml) were added to DMF (5 ml), and the mixture was stirred at room temperature for 1 days. Water was added to the reaction mixture, and stirred for 1 hour, followed by extraction with ethyl acetate. The organic layer was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethylacetate:methanol=85:15). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (0.44 ml) was added to a 2-propanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.20 g) as a white powder. 
         [0997]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 and 0.76 (3H, s), 1.00-1.13 (3H, m), 1.33 and 1.34 (3H, s), 2.92-3.03 (1H, m), 3.10-3.25 (1H, m), 3.30 and 3.30 (3H, s), 3.30-3.50 (3H, m), 3.50-3.81 (3H, m), 3.97-4.14 (1H, m), 4.57-4.91 (4H, m), 6.74-7.11 (3H, m), 7.11-7.40 (3H, m), 7.46 and 7.57 (1H, d, J=8.3 Hz), 7.72-7.85 (1H, m), 8.15-8.37 (1H, m), 8.63-8.86 (2H, m) 
       Example 338 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]benzamide 
       [0998]    The synthesis of the title compound was performed in the same manner as in Example 42 using appropriate starting materials. 
         [0000]    white powder 
         [0999]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, bs), 1.15-1.24 (3H, m), 1.52 and 1.54 (3H, s), 2.43 (3H, d, J=0.4 Hz), 3.33-3.42 (3H, m), 3.45-3.83 (3H, m), 3.83-5.04 (5H, m), 6.27-6.77 (2H, m), 6.80-7.14 (2H, m), 7.17-7.44 (7H, m) 
       Example 339 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(4-methylindol-1-yl)-N-(2-pyridin-3-ylethyl)acetamide hydrochloride 
       [1000]    The synthesis of the title compound was performed in the same manner as in Example 332 using appropriate starting materials. 
         [0000]    white powder 
         [1001]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 and 0.77 (3H, s), 0.90-1.15 (3H, m), 1.33 and 1.35 (3H, s), 2.44 and 2.46 (3H, s), 2.89-3.13 (2H, m), 3.29 and 3.30 (3H, s), 3.58-3.65 (1H, m), 3.66-3.86 (2H, m), 3.96-4.14 (1H, m), 4.56-4.89 (2H, m), 5.10 and 5.20 (2H, s), 6.38-6.50 (1H, m), 6.77-7.03 (3H, m), 7.15-7.36 (3H, m), 7.46 and 7.57 (1H, d, J=8.3 Hz), 7.66-7.78 (1H, m), 8.09-8.23 (1H, m), 8.60-8.79 (2H, m) 
       Example 340 
     7-({N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methoxymethylpyridin-3-ylmethyl)amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1002]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder (Ether) 
       mp: 103-104° C. 
     Example 341 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1003]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 119-122° C. 
     Example 342 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(5-methylthiazol-4-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1004]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 144-145° C. 
     Example 343 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]acetamide 
       [1005]    The synthesis of the title compound was performed in the same manner as in Example 330 using appropriate starting materials. 
         [0000]    white amorphous 
         [1006]      1 H NMR (CDCl 3 ), δ ppm: 0.74 and 0.78 (3H, s), 1.15-1.24 (3H, m), 1.49 and 1.51 (3H, s), 2.41 (3H, d, J=0.6 Hz), 3.11 and 3.24 (3H, s), 3.60-3.94 (9H, m), 3.94-4.26 (2H, m), 4.33-4.78 (2H, m), 6.09-6.59 (2H, m), 6.77-6.90 (1H, m), 6.90-6.98 (1H, m), 7.03-7.37 (5H, m), 7.57 (1H, d, J=8.0 Hz), 7.66 (1H, d, J=8.0 Hz) 
       Example 344 
     7-({N-(1,5-Dimethyl-1H-pyrazol-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4 H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1007]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 138-139° C. 
     Example 345 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)-2-quinolin-3-ylacetamide dihydrochloride 
       [1008]    The synthesis of the title compound was performed in the same manner as in Example 332 using appropriate starting materials. 
         [0000]    white powder 
       mp: 189-194° C. 
     Example 346 
     1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carboxylic acid-N-benzyl-N-(2-pyridin-3-yl-ethyl)amide 
       [1009]    The synthesis of the title compound was performed in the same manner as in Example 330 using appropriate starting materials. 
         [0000]    white powder 
       mp: 181-182° C. 
     Example 347 
     1-Ethyl-3,3,5-trimethyl-7-({N-(5-methyloxazol-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1010]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 129.0-130.5° C. 
     Example 348 
     1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carboxylic acid-N-(4-methoxybenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amide 
       [1011]    The synthesis of the title compound was performed in the same manner as in Example 330 using appropriate starting materials. 
         [0000]    white powder (Et 2 O-EtOH) 
       mp: 151.1-155.1° C. 
     Example 349 
     7-({N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(1,5-dimethyl-1H-pyrazol-3-ylmethyl)amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1012]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 113-116° C. 
     Example 350 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-methylbenzoimidazol-1-yl)-N-(2-pyridin-3-yl-ethyl)acetamide 
       [1013]    The synthesis of the title compound was performed in the same manner as in Example 330 using appropriate starting materials. 
         [0000]    white amorphous 
         [1014]      1 H NMR (CDCl 3 ), δ ppm: 0.82 and 0.87 (3H, s), 1.15-1.30 (3H, m), 1.53 and 1.55 (3H, s), 2.41 and 2.47 (3H, s), 2.87-3.01 (2H, m), 3.33 and 3.39 (3H, s), 3.60-3.94 (3H, m), 4.05-4.26 (1H, m), 4.50-4.87 (4H, m), 6.89 (1H, t, J=8.0 Hz), 6.98-7.60 (7H, m), 7.68 (1H, t, J=9.1 Hz), 8.44 (1H, s), 8.52 and 8.61 (1H, d, J=3.5 Hz) 
       Example 351 
     1-Ethyl-3,3,5-trimethyl-7-({[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-(3-methylpyridin-2-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1015]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder (AcOEt-Et 2 O) 
       mp: 139-143° C. 
     Example 352 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1016]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1017]      1 H NMR (DMSO-d 6 ), δ ppm: 0.69 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.31 (3H, s), 2.80-3.20 (2H, m), 3.29 (3H, s), 3.30 (3H, s), 3.39-3.45 (2H, m), 3.70-3.77 (1H, m), 3.92-4.04 (3H, m), 4.36 (2H, br), 4.74 (2H, br), 6.76 (1H, d, J=6.9 Hz), 7.30-7.40 (3H, m), 7.59 (1H, br), 7.83 (2H, br), 8.07 (1H, d, J=5.2 Hz), 8.65 (2H, br). 
       Example 353 
     7-({N-(1,5-Dimethyl-1H-pyrazol-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1018]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
         [1019]      1 H NMR (DMSO-d 6 ), δ ppm: 0.72 (3H, s), 1.08 (3H, t, J=7.1 Hz), 1.34 (3H, s), 2.24 (3H, s), 3.30-3.43 (5H, m), 3.73 (3H, s), 3.66-3.86 (3H, m), 3.97-4.06 (1H, m), 4.27 (2H, br), 4.43 (2H, br), 6.32-6.35 (1H, m), 6.85 (1H, d, J=7.4 Hz), 6.97 (1H, s), 7.54-7.57 (1H, m), 7.61-7.72 (2H, m), 7.87 (1H, br), 7.94-7.95 (1H, m). 
       Example 354 
     1-Ethyl-7-({N-(6-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1020]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
         [1021]      1 H NMR (DMSO-d 6 ), δ ppm: 0.67 (3H, s), 1.04 (3H, t, J=7.0 Hz), 1.33 (3H, s), 2.40 (3H, s), 2.70-3.10 (2H, m), 3.27 (5H, br), 3.41 (3H, s), 3.65-4.10 (6H, m), 4.63 (2H, br), 6.51 (1H, br), 6.70 (1H, br), 7.57 (1H, d, J=7.2 Hz), 7.00-7.70 (4H, m), 8.23 (1H, br), 8.74 (1H, m). 
       Example 355 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(2-oxo-2,3-dihydrobenzimidazol-1-yl]-N-(2-pyridin-3-ylethyl)isobutyramide 
       [1022]    The synthesis of the title compound was performed in the same manner as in Example 332 using appropriate starting materials. 
         [0000]    pale brown white amorphous 
         [1023]      1 H NMR (CDCl 3 ), δ ppm: 0.74 and 0.80 (3H, s), 1.08-1.23 (3H, m), 1.50 and 1.52 (3H, s), 1.95-2.07 (6H, m), 2.15-2.35 (1H, m), 2.87 (1H, t, J=7.5 Hz), 3.16 and 3.37 (3H, s), 3.42-3.63 (2H, m), 3.63-3.88 (1H, m), 3.95-4.18 (1H, m), 4.43-4.82 (2H, m), 6.52-6.62 (1H, m), 6.80-7.32 (7H, m), 7.48 (1H, d, J=7.8 Hz), 7.99 and 8.10 (1H, s), 8.30-8.63 (2H, m) 
       Example 356 
     1-Ethyl-3,3,5-trimethyl-7-({N-[1-(2-methylpyridin-3-yl)ethyl]-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1024]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder (Ether) 
       mp: 164-167° C. 
     Example 357 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-[1-(2-methylpyridin-3-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1025]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 163-164° C. 
     Example 358 
     7-(1N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-[1-(2-methylpyridin-3-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1026]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 169-170° C. 
     Example 359 
     7-({N-(2-Ethoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1027]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 104-106° C. 
     Example 360 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)-N-(quinolin-5-yl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1028]    1-Ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.45 g), 5-bromoquinoline (0.25 g), tris(dibenzylideneacetone)dipalladium (5.4 mg), xantphos (10 mg), and cesium carbonate (0.46 g) were added to toluene (9 ml), and the mixture was heated at 130° C. for 3 days. The reaction liquid was cooled to room temperature. Water was added to the reaction mixture, and stirred for 1 hour, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The filtrate was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=85:15). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (1 ml) was added to a ethanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.20 g) as a yellow amorphous. 
         [1029]      1 H NMR (DMSO-d 6 ), δ ppm: 0.55 (3H, s), 0.99 (3H, t, J=7.0 Hz), 1.29 (3H, s), 3.03 (2H, t, J=7.1 Hz), 3.14 (3H, s), 3.30-3.80 (3H, m), 3.90-4.03 (1H, m), 4.49 (2H, s), 7.06-7.20 (2H, m), 7.33 (1H, d, J=8.1 Hz), 7.49 (1H, d, J=5.4 Hz), 7.73 (1H, dd, J=4.8 Hz, 8.8 Hz), 7.78-7.90 (3H, m), 8.23 (1H, d, J=8.1 Hz), 8.64 (1H, s), 8.69 (1H, d, J=4.8 Hz), 8.73 (1H, d, J=8.8 Hz), 9.07 (1H, d, J=3.6 Hz), 
       Example 361 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1H-indazol-3-yl)-N-(2-pyridin-3-yl ethyl)acetamide 
       [1030]    The synthesis of the title compound was performed in the same manner as in Example 330 using appropriate starting materials. 
         [0000]    yellow amorphous 
         [1031]      1 H NMR (CDCl 3 ), δ ppm: 0.70 and 0.79 (3H, s), 1.08-1.23 (3H, m), 1.49 and 1.52 (3H, s), 2.77 (1H, t, J=7.7 Hz), 2.85 (1H, t, J=7.3 Hz), 3.06 and 3.21 (3H, s), 3.52-3.82 (3H, m), 4.01-4.16 (3H, m), 4.50-4.70 (2H, m), 6.75-7.32 (5H, m), 7.32-7.50 (3H, m), 7.82-7.92 (1H, m), 8.27-8.55 (2H, m), 10.1 and 10.1 (1H, bs) 
       Example 362 
     7-({N-(4-Chloropyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1032]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 114-118° C. 
     Example 363 
     N-[3-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridin-2-ylmethyl]formamide 
       [1033]    3-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbonitrile (0.40 g) and Raney nickel (1.2 g) were suspended in formic acid (8 ml), and the mixture was stirred at 60° C. for 3 hours. The reaction mixture was filtered to remove insoluble matter, and the filtrate was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=75:25→80:20). The purified product was condensed under reduced pressure. Acetone and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (33 mg) as a pale brown white amorphous. 
         [1034]      1 H NMR (CDCl 3 ), δ ppm: 0.77 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.43 (3H, d, J=0.9 Hz), 2.85 (2H, t, J=5.8 Hz), 3.35 (3H, s), 3.58-3.84 (5H, m), 4.00-4.18 (3H, m), 4.54 (2H, d, J=4.4 Hz), 6.41 (1H, dd, J=0.4 Hz, 7.3 Hz), 6.47 (1H, t, J=0.8 Hz), 6.96 (1H, d, J=7.3 Hz), 7.06 (1H, dd, J=4.9, 7.7 Hz), 7.12-7.20 (3H, m), 7.38 (1H, bs), 7.55 (1H, dd, J=1.2, 7.7 Hz), 8.32 (1H, d, J=1.2 Hz), 8.36 (1H, dd, J=1.5, 4.9 Hz) 
       Example 364 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]N-(quinolin-5-yl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1035]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 166-168° C. 
     Example 365 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indazol-3-yl)-N-(2-pyridin-3-ylethyl)propionamide 
       [1036]    Sodium hydride (55% in oil)(52 mg) was suspended in DMF (7 ml), and cooled to 0° C. in an ice water bath. N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1H-indazol-3-yl)-N-(2-pyridin-3-yl ethyl)acetamide (210 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 30 minutes followed at room temperature for 30 minutes. Methyl iodide (0.03 ml) was added thereto, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=90:10). The purified product was condensed to dryness to give the title compound (20 mg) as a pale yellow white amorphous. 
         [1037]      1 H NMR (CDCl 3 ), δ ppm: 0.75 and 0.86 (3H, s), 1.17 and 1.21 (3H, t, J=7.1 Hz), 1.51 (3H, s), 1.54 (3H, s), 2.94 (1H, t, J=7.7 Hz), 3.06 (1H, t, J=7.2 Hz), 3.40 and 3.48 (3H, s), 3.44-3.54 (2H, m), 3.68 (1H, t, J=6.7 Hz), 3.72-3.90 (1H, m), 3.95-4.22 (2H, m), 4.18 and 4.25 (3H, s), 4.70-4.84 (1H, m), 7.03-7.75 (8H, m), 8.27-8.35 (1H, m), 8.35-8.44 (1H, m), 8.51-8.64 (1H, m) 
       Example 366 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-pyridin-3-ylethyl)formamide 
       [1038]    Sodium hydride (55% in oil) (52 mg) was suspended in DMF (7 ml), and cooled to 0° C. in an ice water bath. N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1H-indazol-3-yl)-N-(2-pyridin-3-yl ethyl)acetamide (210 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 30 minutes followed at room temperature for 30 minutes. Methyl iodide (0.03 ml) was added thereto, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=85:15). The purified product was condensed to dryness to give the title compound (17 mg) as a pale yellow white amorphous. 
         [1039]    pale yellow white amorphous 
         [1040]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.19 and 1.20 (3H, t, J=7.1 Hz), 1.53 (3H, bs), 2.85 (2H, t, J=7.7 Hz), 3.39 and 3.39 (3H, s), 3.44-3.54 (2H, m), 3.75-3.88 (1H, m), 4.06-4.20 (1H, m), 4.27-4.65 (2H, m), 6.98-7.10 (1H, m), 7.10-7.18 (1H, m), 7.21-7.35 (2H, m), 7.41 and 7.53 (1H, dt, J=7.9, 2.0 Hz), 8.05 and 8.30 (1H, s), 8.39 and 8.41 (1H, d, J=1.8 Hz), 8.50 and 8.62 (1H, dd, J=1.8, 4.8 Hz) 
       Example 367 
     1-Ethyl-7-(1N-[1-(2-methoxymethylpyridin-3-yl)ethyl]-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1041]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    white powder 
         [1042]      1 H NMR (DMSO-d 6 ), δ ppm: 0.75 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.34 (3H, s), 1.41 (3H, s), 2.09 (3H, s), 2.57-2.84 (2H, m), 3.16 (2H, br), 3.35 (3H, s), 3.40 (3H, s), 3.62-3.70 (2H, m), 4.00-4.13 (1H, m), 4.18 (2H, br), 6.83 (1H, br), 7.09 (1H, br), 7.43-7.63 (3H, m), 7.83 (1H, br), 7.91-7.92 (1H, m), 8.40 (1H, br), 8.46 (1H, br). 
       Example 368 
     1-Ethyl-7-({N-(2-hydroxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1043]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 187-190° C. 
     Example 369 
     7-({N,N-Bis-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diaz epine-2,4-dione 
       [1044]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 160-165° C. 
     Example 370 
     1-Ethyl-7-({N-(5-methoxymethyl-2-methyl-2H-pyrazol-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1045]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 169-170° C. 
     Example 371 
     1-Ethyl-7-({N-(5-methoxymethyl-2-methyl-2H-pyrazol-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1046]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 113-115° C. 
     Example 372 
     1-Isobutyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1047]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 184-186° C. 
     Example 373 
     1-Isobutyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1048]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 207-210° C. 
     Example 374 
     1-Isobutyl-3,3-dimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1049]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 180-182° C. 
     Example 375 
     1-Isobutyl-3,3-dimethyl-7-({N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1050]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 229-231° C. 
     Example 376 
     1-(2-Methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1051]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 182-185° C. 
     Example 377 
     1-(2-Methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1052]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 188-189° C. 
     Example 378 
     1-Isobutyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1053]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 149-151° C. 
     Example 379 
     1-(2-Methoxyethyl)-3,3-dimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1054]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 179-181° C. 
     Example 380 
     1-(2-Methoxyethyl)-3,3-dimethyl-7-({N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1055]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 205-206° C. 
     Example 381 
     1-Cyclopropylmethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1056]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1057]    ivory powder 
       mp: 189-191° C. 
     Example 382 
     1-Cyclopropylmethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1058]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 192-194° C. 
     Example 383 
     1-Cyclopropylmethyl-3,3-dimethyl-7-(1N-β-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1059]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 138-143° C. 
     Example 384 
     1-Cyclopropylmethyl-3,3-dimethyl-7-(1N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1060]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 220-221° C. 
     Example 385 
     1-Ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(2-oxo-3,4-dihydro-2H-quinolin-1-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1061]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 130-131° C. 
     Example 386 
     1-Cyclopropyl-7-({N-(2-methoxymethyl-pyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1062]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 213-214° C. 
     Example 387 
     1-Cyclopropyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1063]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 182-184° C. 
     Example 388 
     1-Cyclopropyl-3,3-dimethyl-7-({[2-N-(2-methyl-4-oxo-4H-furo[3,2-c ]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1064]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 172-173° C. 
     Example 389 
     1-Cyclopropyl-3,3-dimethyl-7-({N-[2-(7-methyl-4-oxo-4H-furo[3,2-c ]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1065]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 191-193° C. 
     Example 390 
     1-Ethyl-3,3,5-trimethyl-7-({N-(2-methylpyridin-3-ylmethyl)-N-[2-(2-oxo-2H-quinolin-1-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1066]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 149-150° C. 
     Examples 391 to 582 
       [1067]    The following compounds were obtained in the same manner as in Examples above using appropriate starting materials. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
                   
               
             
          
           
               
                   
                 391 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 461 
               
               
                   
                   
               
               
                   
                 392 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 472 
               
               
                   
                   
               
               
                   
                 393 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 472 
               
               
                   
                   
               
               
                   
                 394 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
                   
               
               
                   
                 395 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 477 
               
               
                   
                   
               
               
                   
                 396 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 491 
               
               
                   
                   
               
               
                   
                 397 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 478 
               
               
                   
                   
               
               
                   
                 398 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
                   
               
               
                   
                 399 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
                   
               
               
                   
                 400 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 461 
               
               
                   
                   
               
               
                   
                 401 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 564 
               
               
                   
                   
               
               
                   
                 402 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 540 
               
               
                   
                   
               
               
                   
                 403 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
                   
               
               
                   
                 404 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 492 
               
               
                   
                   
               
               
                   
                 405 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 529 
               
               
                   
                   
               
               
                   
                 406 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 506 
               
               
                   
                   
               
               
                   
                 407 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 492 
               
               
                   
                   
               
               
                   
                 408 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
                   
               
               
                   
                 409 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 492 
               
               
                   
                   
               
               
                   
                 410 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 411 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 412 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 413 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 414 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 415 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
                   
               
               
                   
                 416 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
                   
               
               
                   
                 417 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 506 
               
               
                   
                   
               
               
                   
                 418 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
                   
               
               
                   
                 419 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
                   
               
               
                   
                 420 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 421 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
                   
               
               
                   
                 422 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 540 
               
               
                   
                   
               
               
                   
                 423 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 502 
               
               
                   
                   
               
               
                   
                 424 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 478 
               
               
                   
                   
               
               
                   
                 425 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 478 
               
               
                   
                   
               
               
                   
                 426 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
                   
               
               
                   
                 427 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 462 
               
               
                   
                   
               
               
                   
                 428 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
                   
               
               
                   
                 429 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 430 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 502 
               
               
                   
                   
               
               
                   
                 431 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 476 
               
               
                   
                   
               
               
                   
                 432 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
                   
               
               
                   
                 433 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 462 
               
               
                   
                   
               
               
                   
                 434 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 462 
               
               
                   
                   
               
               
                   
                 435 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 476 
               
               
                   
                   
               
               
                   
                 436 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 
               
               
                   
                   
               
               
                   
                 437 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
                   
               
               
                   
                 438 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 500 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 439 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 440 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 441 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 442 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 443 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 533 
               
               
                   
               
               
                 444 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 547 
               
               
                   
               
               
                 445 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 446 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 447 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 448 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 449 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 620 
               
               
                   
               
               
                 450 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 451 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 452 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 453 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 585 
               
               
                   
               
               
                 454 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 455 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 456 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 561 
               
               
                   
               
               
                 457 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 458 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 459 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 460 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 461 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 462 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 463 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 464 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 465 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 466 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 467 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 468 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 469 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 470 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 471 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 472 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 473 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 474 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 529 
               
               
                   
               
               
                 475 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 476 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 529 
               
               
                   
               
               
                 477 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 478 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 479 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 532 
               
               
                   
               
               
                 480 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 481 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 482 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 483 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 532 
               
               
                   
               
               
                 484 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 616 
               
               
                   
               
               
                 485 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 486 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 487 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 527 
               
               
                   
               
               
                 488 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 538 
               
               
                   
               
               
                 489 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 538 
               
               
                   
               
               
                 490 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 541 
               
               
                   
               
               
                 491 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 492 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 493 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 544 
               
               
                   
               
               
                 494 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 495 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 553 
               
               
                   
               
               
                 496 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 527 
               
               
                   
               
               
                 497 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 630 
               
               
                   
               
               
                 498 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 606 
               
               
                   
               
               
                 499 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 500 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 501 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 595 
               
               
                   
               
               
                 502 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
               
               
                 503 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 504 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 505 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 506 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 507 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 508 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 509 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 510 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 511 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 512 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 541 
               
               
                   
               
               
                 513 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
               
               
                 514 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 515 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 541 
               
               
                   
               
               
                 516 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 517 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 518 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 606 
               
               
                   
               
               
                 519 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 568 
               
               
                   
               
               
                 520 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 544 
               
               
                   
               
               
                 521 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 544 
               
               
                   
               
               
                 522 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 539 
               
               
                   
               
               
                 523 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 524 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 539 
               
               
                   
               
               
                 525 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 526 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 568 
               
               
                   
               
               
                 527 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 528 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 552 
               
               
                   
               
               
                 529 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 530 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 531 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 532 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 626 
               
               
                   
               
               
                 533 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 553 
               
               
                   
               
               
                 534 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 566 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 535 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 536 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 537 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
               
                 538 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 539 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 533 
               
               
                   
               
               
                 540 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 547 
               
               
                   
               
               
                 541 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 542 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 543 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 544 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 545 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 620 
               
               
                   
               
               
                 546 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 547 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 548 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 549 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 585 
               
               
                   
               
               
                 550 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 551 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 552 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 561 
               
               
                   
               
               
                 553 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 548 
               
               
                   
               
               
                 554 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 555 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 556 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 557 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 558 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 559 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 560 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 561 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 562 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 563 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 531 
               
               
                   
               
               
                 564 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 565 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 566 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 567 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 568 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 569 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 570 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 529 
               
               
                   
               
               
                 571 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 572 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 529 
               
               
                   
               
               
                 573 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 574 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 558 
               
               
                   
               
               
                 575 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 532 
               
               
                   
               
               
                 576 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 542 
               
               
                   
               
               
                 577 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 578 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 579 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 532 
               
               
                   
               
               
                 580 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 616 
               
               
                   
               
               
                 581 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 543 
               
               
                   
               
               
                 582 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
             
          
         
       
     
       Example 583 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyrimidin-5-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1068]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 146.2-148.2° C. 
     Example 584 
     1-Ethyl-3,3,5-trimethyl-7-[4-(2-oxo-3,4-dihydro-2H-quinolin-1-yl)piperidin-1-ylmethyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1069]    1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (0.203 g) and acetic acid (0.063 ml) were added to a 1,2-dichloroethane solution (5 ml) of 1-(piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (0.170 g), and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (0.235 g) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=100:0-90:10). The purified product was condensed to dryness to give the title compound (0.205 g) as pale yellow amorphous. 
         [1070]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.20 (3H, t, J=7.1 Hz), 1.54 (3H, s), 1.68-1.75 (2H, m), 2.13-2.21 (2H, m), 2.55-2.60 (2H, m), 2.64-2.76 (2H, m), 2.80-2.85 (2H, m), 2.95-3.03 (2H, m), 3.44 (3H, s), 3.57 (2H, s), 3.77-3.85 (1H, m), 4.10-4.19 (1H, m), 4.25-4.33 (1H, m), 7.01 (1H, dt, J=1.9, 7.4 Hz), 7.14-7.28 (6H, m) 
       Example 585 
     1-Ethyl-3,3,5-trimethyl-7-[4-(2-oxo-2H-quinolin-1-yl)-piperidin-1-ylmethyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1071]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1072]      1 H NMR (CDCl 3 ), δ ppm: 0.85 (3H, s), 1.21 (3H, t, J=7.0 Hz), 1.54 (3H, s), 1.70-1.77 (2H, m), 2.28-2.34 (2H, m), 2.94 (2H, br), 3.05-3.13 (2H, m), 3.46 (3H, s), 3.64 (2H, s), 3.78-3.87 (1H, m), 4.11-4.19 (1H, m), 5.33 (1H, bs), 6.67 (1H, d, J=9.4 Hz), 7.21 (1H, t, J=8.0 Hz), 7.27-7.32 (3H, m), 7.50-7.57 (2H, m), 7.62 (1H, d, J=9.4 Hz), 7.78 (1H, br) 
       Example 586 
     N-[1-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)piperidin-4-yl]-N-phenylbenzamide 
       [1073]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1074]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.55-1.63 (2H, m), 1.88-1.95 (2H, m), 2.16-2.26 (2H, m), 2.88-2.94 (2H, m), 3.38 (3H, s), 3.45-3.53 (2H, m), 3.73-3.82 (1H, m), 4.10-4.16 (1H, m), 4.70-4.82 (1H, m), 6.98-7.02 (2H, m), 7.07-7.24 (11H, m) 
       Example 587 
     1-Ethyl-3,3,5-trimethyl-7-[3-(2-oxo-3,4-dihydro-2H-quinolin-1-yl)-pyrrolidin-1-ylmethyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1075]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1076]      1 H NMR (CDCl 3 ), δ ppm: 0.73-0.82 (3H, m), 1.16-1.20 (3H, m), 1.51-1.53 (3H, m), 2.10-2.35 (2H, m), 2.55-3.20 (8H, m), 3.40-3.44 (3H, m), 3.61-4.16 (4H, m), 5.30-5.45 (1H, m), 6.98-7.04 (1H, m), 7.14-7.30 (5H, m), 7.65-7.68 (1H, m) 
       Example 588 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(2-oxo-1,2,3,4-tetrahydroquinolin-6-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1077]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1078]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.18 (3H, t, J=7.0 Hz), 1.52 (3H, s), 2.48 (3H, s), 2.62-2.65 (2H, m), 2.94-2.98 (2H, m), 3.39 (3H, s), 3.46-3.59 (6H, m), 3.76-3.82 (1H, m), 4.09-4.13 (1H, m), 6.71 (1H, d, J=8.0 Hz), 7.09-7.17 (4H, m), 7.21-7.24 (2H, m), 7.68 (1H, dd, J=1.6, 7.7 Hz), 7.91 (1H, br), 8.38 (1H, dd, J=1.7, 4.9 Hz) 
       Example 589 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(2-methylpyridin-3-ylmethyl)-N-(2-oxo-1,2,3,4-tetrahydroquinolin-7-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1079]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1080]      1 H NMR (CDCl 3 ), 6 ppm: 0.80 (3H, s), 1.18 (3H, t, J=7.0 Hz), 1.52 (3H, s), 2.50 (3H, s), 2.62-2.65 (2H, m), 2.94-2.97 (2H, m), 3.39 (3H, s), 3.49-3.61 (6H, m), 3.76-3.84 (1H, m), 4.09-4.13 (1H, m), 6.74 (1H, d, J=1.1 Hz), 6.97 (1H, dd, J=1.4, 7.7 Hz), 7.10-7.13 (2H, m), 7.16 (1H, d, J=1.1 Hz), 7.22-7.28 (2H, m), 7.70 (1H, dd, J=1.6, 7.7 Hz), 8.17 (1H, br), 8.38 (1H, dd, J=1.6, 4.9 Hz) 
       Example 590 
     7-{[N-(1-Benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1081]    1-Benzyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-carbaldehyde (0.205 g) was added to a methanol solution (10 ml) of 7-(aminomethyl)-1-ethyl-3,3,5-trimethyl-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione (0.213 g). The mixture was stirred at room temperature overnight. Sodium borohydride (0.022 g) was added to the mixture, and the mixture was stirred at room temperature overnight. The liquid was then condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1). The purified product was condensed under reduced pressure to give the title compound (0.400 g) as a white amorphous.  1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.77-2.81 (2H, m), 2.96-3.00 (2H, m), 3.40 (3H, s), 3.73 (2H, s), 3.74-3.83 (1H, m), 3.81 (2H, s), 4.12-4.17 (1H, m), 5.17 (2H, s), 6.83 (1H, d, J=8.3 Hz), 7.05 (1H, dd, J=1.9, 8.3 Hz), 7.16 (1H, d, J=1.6 Hz), 7.19-7.25 (6H, m), 7.27-7.33 (2H, m) 
       Example 591 
     7-{[N-(1-Benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1082]    The synthesis of the title compound was performed in the same manner as in Example 590 using appropriate starting materials. 
         [1083]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.18 (3H, t, J=7.0 Hz), 1.53 (3H, s), 2.77-2.80 (2H, m), 2.96-3.00 (2H, m), 3.38 (3H, s), 3.67 (2H, s), 3.68 (2H, s), 3.76-3.81 (1H, m), 4.12-4.18 (1H, m), 5.20 (2H, s), 6.90-6.95 (2H, m), 7.09 (1H, dd, J=1.8, 8.4 Hz), 7.12-7.14 (2H, m), 7.17-7.24 (4H, m), 7.25-7.30 (2H, m) 
       Example 592 
     1-Cyclopropyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1084]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    ivory powder 
       mp: 146-148° C. 
     Example 593 
     1-(2-Methoxyethyl)-3,3,5-trimethyl-7-({N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1085]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    white powder 
       mp: 127-130° C. 
     Example 594 
     1-Ethyl-3,3,5-trimethyl-7-(2-phenylpiperidin-1-ylmethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1086]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1087]      1 HNMR (CDCl 3 ), δ ppm: 0.78 and 0.81 (3H, s), 1.15-1.20 (3H, m), 1.33-1.47 (1H, m), 1.51-1.53 (3H, m), 1.55-1.84 (5H, m), 1.95-2.05 (1H, m), 2.83-2.97 (2H, m), 3.12-3.17 (1H, m), 3.38 and 3.41 (3H, s), 3.70-3.85 (2H, m), 4.07-4.18 (1H, m), 7.07-7.26 (4H, m), 7.30-7.36 (2H, m), 7.40-7.45 (2H, m) 
       Example 595 
     1-Cyclopropyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-m ethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1088]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    White powder 
         [1089]      1 H NMR (DMSO-d 6 ), δ ppm: −0.27-0.01 (1H, m), 0.43-0.46 (1H, m), 0.74 (3H, s), 0.73-0.79 (1H, m), 1.05-1.34 (1H, m), 1.34 (3H, s), 2.16 (3H, s), 2.81 (2H, br), 3.21-3.28 (1H, m), 3.28 (3H, s), 3.28 (3H, s), 3.84 (4H, br), 4.15 (2H, br), 4.55 (2H, br), 6.93 (1H, s), 7.36 (2H, br), 7.43 (2H, br), 7.77 (1H, br), 7.97 (1H, d, J=2.1 Hz), 8.38 (1H, s), 8.60 (1H, br). 
       Example 596 
     1-(2-Methoxyethyl)-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1090]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [0000]    White powder 
         [1091]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 (3H, s), 1.35 (3H, s), 2.43 (3H, s), 2.51 (3H, s), 2.80 (2H, br), 3.12 (3H, s), 3.29 (3H, s), 3.41 (2H, t, J=5.2 Hz), 3.83 (2H, br), 3.85-3.88 (2H, m), 4.00-4.60 (4H, m), 6.46 (1H, s), 6.23 (1H, s), 7.10-7.49 (4H, m), 7.71 (1H, br), 8.28 (1H, br), 8.56 (1H, br). 
       Example 597 
     7-{N-(Benzo[1,3]dioxol-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]aminomethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1092]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 135.9-137.5° C. 
     Example 598 
     1-Ethyl-3,3,5-trimethyl-7-{N-[3-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)benzylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1093]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. White amorphous 
         [1094]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.77-2.83 (2H, m), 2.97-3.02 (2H, m), 3.41 (3H, s), 3.76-3.83 (5H, m), 4.10-4.18 (1H, m), 5.17 (2H, s), 6.86 (1H, d, J=8.2 Hz), 6.97 (1H, dt, J=1.0 and 7.4 Hz), 7.07-7.14 (2H, m), 7.17-7.29 (7H, m) 
       Example 599 
     1-Ethyl-7-({N-(1H-indol-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1095]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
         [1096]      1 H NMR (CDCl 3 ), δ ppm: 0.65 (3H, s), 1.08 (3H, t, J=7.1 Hz), 1.47 (3H, s), 2.48 (3H, d, J=1.0 Hz), 2.86 (2H, t, J=5.1 Hz), 3.13 (3H, s), 3.41 (2H, s), 3.61-3.72 (1H, m), 3.91-4.17 (3H, m), 4.22-4.35 (1H, m), 4.35-4.43 (1H, m), 6.24 (1H, dd, J=0.62, 7.4 Hz), 6.47 (1H, dd, J=2.0, 3.0 Hz), 6.67 (1H, d, J=0.84 Hz), 6.73-6.84 (3H, m), 6.89 (1H, d, J=1.4 Hz), 6.95-7.03 (2H, m), 7.17 (1H, t, J=2.8 Hz), 7.52-7.59 (1H, m), 10.51 (1H, s). 
       Example 600 
     7-{N-(Benzo[1,3]dioxol-5-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]aminomethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1097]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 179.7-181.8° C. 
     Example 601 
     1-Ethyl-7-({N-(1H-indol-6-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1098]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. White amorphous 
         [1099]      1 H NMR (CDCl 3 ), δ ppm: 0.76 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.50 (3H, s), 2.44 (3H, d, J=1.0 Hz), 2.86 (2H, dt, J=2.4, 5.9 Hz), 3.31 (3H, s), 3.62-3.83 (5H, m), 3.98-4.18 (3H, m), 6.40 (1H, dd, J=0.70, 7.3 Hz), 6.48 (1H, t, J=0.88 Hz), 6.50-6.54 (1H, m), 6.95-7.11 (4H, m), 7.15 (1H, bs), 7.19 (1H, dd, J=2.5, 3.1 Hz), 7.53 (1H, d, J=8.1 Hz), 8.10 (1H, bs). 
       Example 602 
     7-({N-(1H-Benzoimidazol-5-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1100]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. White amorphous 
         [1101]      1 H NMR (CDCl 3 ), δ ppm: 0.76 (3H, s), 1.16 (3H, t, J=7.0 Hz), 1.51 (3H, s), 2.43 (3H, d, J=0.68 Hz), 2.80-2.92 (2H, m), 3.33 (3H, s), 3.62-3.88 (5.H, m), 3.92-4.25 (3H, m), 6.40 (1H, d, J=7.4 Hz), 6.47 (1H, s), 6.82-7.25 (5H, m), 7.26-7.92 (2H, m), 8.02 (1H, s), 9.38 (1H, bs). 
       Example 603 
     1-Isobutyl-3,3-dimethyl-8-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1102]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ethyl acetate-hexane-diisopropyl ether) 
       mp: 128-130° C. 
     Example 604 
     1-Isobutyl-3,3-dimethyl-8-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1103]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 206-208° C. 
     Example 605 
     1-Isobutyl-8-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1104]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    Pale pink powder (ethyl acetate-hexane-diisopropyl ether) 
       mp: 155-159° C. 
     Example 606 
     1-Ethyl-3,3,5-trimethyl-7-({N-(3-methylimidazo[1,5-a]pyridin-1-yl methyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1105]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 104.1-109.4° C. 
     Example 607 
     1-Cyclopropylmethyl-3,3-dimethyl-8-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1106]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Ivory powder (ethyl acetate-hexane-diisopropyl ether) 
       mp: 153-155° C. 
     Example 608 
     1-Cyclopropylmethyl-3,3-dimethyl-8-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-N-(2-methylpyridin-3-ylmethyl)amino] m  ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1107]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Ivory powder (Ether) 
       mp: 207-210° C. 
     Example 609 
     1-Cyclopropylmethyl-8-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1108]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 139-141° C. 
     Example 610 
     1-Isobutyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1109]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Ivory powder (Ether) 
       mp: 151-152° C. 
     Example 611 
     1-Ethyl-3,3,5-trimethyl-7-({N-[(1-methyl-1H-benzoimidazol-2-yl)methyl]-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1110]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 126.9-132.6° C. 
     Example 612 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-pyrazol-1-ylbenzyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1111]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. White amorphous 
         [1112]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.44 (3H, d, J=1.0 Hz), 2.86 (2H, dt, J=1.8, 5.8 Hz), 3.30 (3H, s), 363-3.84 (5H, m), 3.98-4.23 (3H, m), 6.37 (1H, dd, J=0.68, 7.3 Hz), 6.49 (1H, t, J=0.88 Hz), 6.95 (1H, d, J=7.4 Hz), 7.03-7.15 (3H, m), 7.16-7.26 (4H, m), 7.32 (1H, d, J=7.7 Hz), 7.32-7.37 (1H, m), 7.83 (1H, t, J=1.1 Hz). 
       Example 613 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-pyrazol-1-yl-benzyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1113]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    Pale yellow white powder 
       mp: 123-130° C. 
     Example 614 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]pyrazin-2-ylmethylamino}methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1114]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 128.7-130.7° C. 
     Example 615 
     1-Ethyl-7-({N-(imidazo[1,2-a]pyridin-2-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1115]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials.  1 H NMR (CDCl 3 ), δ ppm: 0.76 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.50 (3H, s), 2.43 (3H, d, J=0.72 Hz), 2.91 (2H, t, J=5.5 Hz), 3.32 (3H, s), 3.69-3.85 (3H, m), 3.85-3.95 (2H, m), 3.95-4.22 (3H, m), 6.43 (1H, dd, J=0.68, 7.3 Hz), 6.48 (1H, s), 6.76 (1H, dt, J=1.1, 6.8 Hz), 7.02-7.11 (2H, m), 7.12-7.23 (3H, m), 7.32 (1H, s), 7.53 (1H, q, J=3.2 Hz), 7.95 (1H, td, J=1.1, 6.8 Hz). 
       Example 616 
     7-{[N-(1-Benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-ylmethyl)-N-methylamino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione 
       [1116]    7-{[N-(1-Benzyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-ylmethyl) amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]di azepine-2,4-dione (247 mg) was dissolved in DMF (2 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 13.56 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (73.5 mg) was added thereto, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (169 mg) as a white amorphous. 
         [1117]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.04 (3H, s), 2.75-2.8 (2H, m), 2.95-3.00 (2H, m), 3.38 (3H, s), 3.40-3.44 (4H, m), 3.75-3.85 (1H, m), 4.07-4.19 (1H, m), 5.20 (2H, s), 6.92-6.96 (2H, m), 7.07-7.14 (3H, m), 7.17-7.31 (6H, m) 
       Example 617 
     1-Ethyl-7-({N-(2-hydroxybenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1118]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 166-170° C. 
     Example 618 
     1-Isobutyl-8-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1119]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ethyl acetate-hexanes) 
       mp: 96-100° C. 
     Example 619 
     1-Cyclopropylmethyl-8-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1120]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ethyl acetate-hexane) 
       mp: 95-99° C. 
     Example 620 
     2-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzonitrile 
       [1121]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 156.7-158.6° C. 
     Example 621 
     4-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde 
       [1122]    A 2N-hydrochloric acid (5 ml) was added to an THF solution (5 ml) of 7-({N-(4-diethoxymethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c ]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dih ydro-benzo[b][1,4]diazepine-2,4-dione (0.52 g), and the mixture was stirred at room temperature for 1 hour. 2N-Sodium hydroxide solution (5 ml) was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The purified product was condensed under reduced pressure. The residue was recrystallized from ethyl acetate and ether, and dried to give the title compound (0.35 g) as a white powder. 
       mp: 153-155° C. 
     Example 622 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-oxo-2H-quinolin-1-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1123]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 152-153° C. 
     Example 623 
     1-Ethyl-7-({N-(6-methoxy-2-methylpyridin-3-ylmethyl)-N-[2-(2-oxo-2H-quinolin-1-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1124]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 143-144° C. 
     Example 624 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-oxo-3,4-dihydro-2H-quinolin-1-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1125]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 112-114° C. 
     Example 625 
     1,3,3-Trimethyl-8-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methyl-pyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1126]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Ivory powder (Ether) 
       mp: 117-122° C. 
     Example 626 
     1,3,3-Trimethyl-8-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1127]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 154-157° C. 
     Example 627 
     1-Ethyl-3,3-dimethyl-8-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyrid in-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1128]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 108-114° C. 
     Example 628 
     1-Ethyl-3,3-dimethyl-8-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyrid in-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1129]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 177-179° C. 
     Example 629 
     1-Ethyl-7-({N-(6-methoxy-2-methylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1130]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 155-156° C. 
     Example 630 
     1,3,3-Trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methyl-pyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1131]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 176-178° C. 
     Example 631 
     1,3,3-Trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1132]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Pale pink powder (Ether) 
       mp: 142-144° C. 
     Example 632 
     1-Ethyl-3,3-dimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyrid in-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1133]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 213-215° C. 
     Example 633 
     1-Ethyl-3,3-dimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1134]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 197-199° C. 
     Example 634 
     1-Ethyl-3,3,5-trimethyl-7-({N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(pyridazin-4-ylmethyl)amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1135]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 137-141° C. 
     Example 635 
     1-Ethyl-3,3,5-trimethyl-7-({[N-(1-methyl-1H-indazol-3-yl)methyl]-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1136]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 96-102° C. 
     Example 636 
     1-Ethyl-3,3,5-trimethyl-7-({N-(7-methyl-1H-indazol-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1137]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 111-118° C. 
     Example 637 
     1-Ethyl-3,3,5-trimethyl-7-(3-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]amino}propyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1138]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1139]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 (3H, s), 1.04 (3H, t, J=7.0 Hz), 1.32 (3H, s), 2.62-4.68 (20H, m), 6.69-8.75 (12H, m), 
       Example 638 
     1-Ethyl-3,3,5-trimethyl-7-(3-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1140]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 150.9-154.7° C. 
     Example 639 
     1-Ethyl-3,3,5-trimethyl-7-{3-[N-(2-methylpyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1141]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1142]      1 H NMR (DMSO-d 6 ), δ ppm: 0.72 (3H, s), 1.04 (3H, t, J=7.0 Hz), 1.33 (3H, s), 2.09-3.79 (18H, m), 4.65 (2H, br-s), 7.22 (1H, d, J=8.0 Hz), 7.33 (1H, s), 7.43 (1H, d, J=8.4 Hz), 7.83 (1H, t, J=6.6 Hz) 7.93-7.97 (1H, m), 8.44 (1H, d, J=7.5 Hz), 8.76-8.80 (3H, m), 8.90 (1H, s) 
       Example 640 
     1-Ethyl-3,3,5-trimethyl-7-(3-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(7-oxo-7H-furo[2,3-c]pyridin-6-yl)ethyl]amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1143]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 106.4-114.6° C. 
     Example 641 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1144]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 128.2-130.9° C. 
     Example 642 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1145]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 171-173° C. 
     Example 643 
     1-Ethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1146]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 168-170° C. 
     Example 644 
     8-({N-(2-Methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,3,3-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1147]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 179-182° C. 
     Example 645 
     8-({N-(2-Methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,3,3-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1148]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 123-134° C. 
     Example 646 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-3,3-dimethyl-7-{[N-[2-(7-m ethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1149]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 159-160° C. 
     Example 647 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1150]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 131-135° C. 
     Example 648 
     7-[2-(4-Chlorophenyl)pyrrolidin-1-ylmethyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1151]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1152]      1 H NMR (CDCl 3 ), δ ppm: 0.79 and 0.80 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.65-1.98 (3H, m), 2.15-2.30 (2H, m), 3.05-3.17 (2H, m), 3.35-3.45 (4H, m), 3.70-3.83 (2H, m), 4.08-4.18 (1H, m), 7.06-7.23 (3H, m), 7.27-7.32 (2H, m), 7.34-7.38 (2H, m) 
       Example 649 
     7-(3-Benzylpiperidin-1-ylmethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1153]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1154]      1 H NMR (CDCl 3 ), δ ppm: 0.77 and 0.79 (3H, s), 0.97-2.10 (5H, m), 1.18 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.45-2.55 (2H, m), 2.80-2.90 (2H, m), 3.35 and 3.40 (3H, s), 3.41-3.60 (4H, m), 3.75-3.85 (1H, m), 4.10-4.20 (1H, m), 7.08-7.26 (8H, m) 
       Example 650 
     1-Ethyl-3,3,5-trimethyl-7-(2-phenylazetidin-1-ylmethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1155]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1156]      1 H NMR (CDCl 3 ), δ ppm: 0.70 and 0.71 (3H, s), 1.10-1.15 (3H, m), 1.50 (3H, s), 2.10-2.20 (1H, m), 2.32-2.40 (1H, m), 2.90-3.01 (1H, m), 3.26 and 3.32 (3H, s), 3.41-3.46 (1H, m), 3.58-3.78 (3H, m), 4.07-4.17 (2H, m), 7.07-7.21 (4H, m), 7.22-7.28 (2H, m), 7.33-7.38 (2H, m) 
       Example 651 
     1-Ethyl-3,3,5-trimethyl-7-(6-methyl-3′,4′,5′,6′-tetrahydro-2′H-[2,3′]bipyridinyl-1′-ylmethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1157]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1158]      1 H NMR (CDCl 3 ), δ ppm: 0.81 and 0.82 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.54-1.83 (3H, m), 1.95-2.02 (1H, m), 2.03-2.14 (1H, m), 2.18-2.26 (1H, m), 2.51 (3H, s), 2.81-2.90 (1H, m), 2.95-3.10 (2H, m), 3.41 and 3.42 (3H, s), 3.50-3.60 (2H, m), 3.75-3.85 (1H, m), 4.08-4.17 (1H, m), 6.95-6.98 (2H, m), 7.21-7.24 (3H, m), 7.45-7.50 (1H, m) 
       Example 652 
     7-(2-Benzylpyrrolidin-1-ylmethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1159]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1160]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.53-1.83 (4H, m), 2.15-2.25 (1H, m), 2.53-2.63 (1H, m), 2.68-2.76 (1H, m), 2.88-3.06 (2H, m), 3.26-3.35 (1H, m), 3.42 and 3.43 (3H, s), 3.75-3.85 (1H, m), 4.03-4.20 (2H, m), 7.17-7.30 (8H, m) 
       Example 653 
     1-Ethyl-3,3,5-trimethyl-7-[(2-phenoxypyridin-3-ylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1161]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. White amorphous 
         [1162]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.20 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.39 (3H, s), 3.75-3.85 (1H, m), 4.09-4.19 (1H, m), 4.45 (2H, d, J=5.8 Hz), 4.89 (1H, t, J=5.8 Hz), 6.80 (1H, dd, J=1.7 and 7.8 Hz), 6.85 (1H, dd, J=4.8 and 7.8 Hz), 7.13-7.23 (3H, m), 7.24-7.34 (3H, m), 7.38-7.43 (2H, m), 7.51 (1H, dd, J=1.7 and 4.8 Hz) 
       Example 654 
     7-[(1-Benzyl-1H-pyrazol-4-ylamino)methyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1163]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. Pale brown amorphous 
         [1164]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.0 Hz), 1.51 (3H, s), 3.36 (3H, s), 3.75-3.82 (1H, m), 4.08-4.15 (1H, m), 4.17 (2H, s), 5.18 (2H, s), 6.85 (1H, d, J=0.8 Hz), 7.15-7.20 (3H, m), 7.21-7.35 (6H, m) 
       Example 655 
     7-[(3-Benzyloxypyrazin-2-ylamino)methyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1165]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [0000]    Pale yellow amorphous 
         [1166]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 3.37 (3H, s), 3.75-3.83 (1H, m), 4.07-4.15 (1H, m), 4.68 (2H, d, J=6.1 Hz), 5.41 (2H, s), 5.46 (1H, t, J=6.1 Hz), 7.20-7.25 (3H, m), 7.35-7.43 (4H, m), 7.44-7.47 (2H, m), 7.61 (1H, d, J=3.2 Hz) 
       Example 656 
     1-Ethyl-3,3,5-trimethyl-7-(3-phenethylpiperidin-1-ylmethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1167]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1168]      1 H NMR (CDCl 3 ), δ ppm: 0.82 and 0.83 (3H, s), 0.90-1.00 (1H, m), 1.19 (3H, t, J=7.1 Hz), 1.50-1.75 (6H, m), 1.53 (3H, s), 1.80-1.88 (1H, m), 1.90-2.00 (1H, m), 2.50-2.60 (2H, m), 2.71-2.84 (2H, m), 3.40 and 3.41 (3H, s), 3.45-3.52 (2H, m), 3.75-3.85 (1H, m), 4.10-4.20 (1H, m), 7.10-7.30 (8H, m) 
       Example 657 
     1-Ethyl-3,3,5-trimethyl-7-[(4-phenoxymethylthiazol-2-ylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1169]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. White amorphous 
         [1170]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.39 (3H, s), 3.76-3.85 (1H, m), 4.09-4.19 (1H, m), 4.53 (2H, d, J=5.0 Hz), 5.04 (2H, s), 5.69 (1H, brs), 6.54 (1H, s), 6.95-7.00 (3H, m), 7.23-7.32 (5H, m) 
       Example 658 
     1-Ethyl-3,3,5-trimethyl-7-[2-(4-trifluoromethylphenyl)pyrrolidin-1-ylmethyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1171]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1172]      1 H NMR (CDCl 3 ), δ ppm: 0.79 and 0.80 (3H, s), 1.16 (3H, t, J=7.0 Hz). 1.52 (3H, s), 1.68-2.00 (3H, m), 2.20-2.32 (2H, m), 3.10-3.23 (2H, m), 3.39 (3H, s), 3.47-3.51 (1H, m), 3.70-3.82 (2H, m), 4.09-4.16 (1H, m), 7.07-7.23 (3H, m), 7.53-7.62 (4H, m) 
       Example 659 
     7-[2-(2-Chlorophenyl)pyrrolidin-1-ylmethyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1173]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1174]      1 H NMR (CDCl 3 ), δ ppm: 0.79 and 0.80 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.55-1.70 (1H, m), 1.75-1.95 (2H, m), 2.28-2.45 (2H, m), 3.12-3.18 (1H, m), 3.25-3.30 (1H, m), 3.39 and 3.40 (3H, s), 3.71-3.85 (2H, m), 3.92-4.00 (1H, m), 4.09-4.20 (1H, m), 7.11-7.22 (4H, m), 7.24-7.34 (2H, m), 7.73-7.78 (1H, m) 
       Example 660 
     7-[2-(3-Chlorophenyl)pyrrolidin-1-ylmethyl]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1175]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1176]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.14-1.19 (3H, m), 1.52 (3H, s), 1.65-2.00 (3H, m), 2.17-2.31 (2H, m), 3.06-3.22 (2H, m), 3.35-3.44 (4H, m), 3.73-3.81 (2H, m), 4.08-4.16 (1H, m), 7.06-7.30 (6H, m), 7.43-7.47 (1H, m) 
       Example 661 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-3,3-dimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1177]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (diisopropyl ether) 
       mp: 127-128° C. 
     Example 662 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-3,3-dimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1178]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 131° C. 
     Example 663 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-3,3-dimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1179]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (Ether) 
       mp: 146-148° C. 
     Example 664 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1180]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ether) 
       mp: 128-129° C. 
     Example 665 
     Acetic acid 3-({N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridin-2-ylmethyl ester 
       [1181]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1182]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.09 (3H, s), 2.43 (1H, d, J=0.96 Hz), 2.84 (2H, t, J=6.4 Hz), 3.35 (3H, s), 3.66-3.80 (5H m), 4.02-4.15 (3H, m), 5.16 (2H, s), 6.40 (1H, d, J=7.3 Hz), 6.50 (1H, br), 6.88 (1H, d, J=7.3 Hz), 7.07-7.19 (4H, m), 7.58 (1H, dd, J=7.8, 1.6 Hz), 8.46 (1H, dd, J=4.8, 1.6 Hz). 
       Example 666 
     1-Ethyl-7-({N-(2-hydroxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1183]    Potassium carbonate (2.0 g) was added to a methanol solution (30 mL) of (3-((((1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)methyl) (2-(2-methyl-4-oxofuro[3,2-c]pyridin-5(4H)-yl)ethyl)amino)methyl)pyridin-2-yl)methyl acetate (3.0 g) and the mixture was stirred overnight at room temperature. The resulting mixture was filtered and evaporated. The residue was purified by column-chromatography (methanol:ethyl acetate=0:100→1:9) to give the titled compound as ivory powder (1.95 g). 
       mp: 186-188° C. 
     Example 667 
     5-Cyclopropyl-1-cyclopropylmethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1184]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder (ethyl acetate-hexane) 
       mp: 121-122° C. 
     Example 668 
     1-Ethyl-3,3,5-trimethyl-7-{3-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1185]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 134.7-134.8° C. 
     Example 669 
     3-(1N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbaldehyde 
       [1186]    2-iodoxybenzoic acid (IBX, 0.235 g) was added to the dimethyl sulfoxide suspension (10 mL) of 1-ethyl-7-((N-((2-(hydroxymethyl)pyridin-3-yl)methyl)-N-(2-(2-methyl-4-oxofuro[3,2-c]pyridin-5(4H)-yl)ethyl)amino)methyl)-3,3,5-trimethyl-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione (0.48 g) and the mixture was stirred overnight at room temperature. Water was added to the resulting mixture and then the mixture was extracted with ethyl acetate twice. The combined organic layer was concentrated under reduced pressure, and then the residue was purified by column-chromatography (ethyl acetate:hexanes=50:50→100:0). The purified product was recrystallized from ether to afford the titled compound as ivory powder (0.29 g). 
       mp: 147-149° C. 
     Example 670 
     1-Ethyl-3,3,5-trimethyl-7-{[(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1187]    Trifluoroacetic acid (43.2 mg) was added to a dichloromethane solution (5 ml) of N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)carbamic acid tert-butyl ester (208 mg), and the mixture was stirred at room temperature overnight. A saturated sodium bicarbonate solution was added to the reaction mixture, followed by extraction using dichloromethane, and condensed under reduced pressure to give the title compound (148 mg) as a white amorphous. 
         [1188]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.62-2.67 (2H, m), 2.86-2.93 (2H, m), 3.37 (3H, s), 3.42 (3H, s), 3.75-3.86 (5H, m), 4.10-4.17 (1H, m), 6.97-7.02 (2H, m), 7.12-7.15 (1H, m), 7.22-7.29 (3H, m) 
       Example 671 
     1-Ethyl-3,3,5-trimethyl-7-{[(2-oxo-1-pyridin-4-ylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1189]    The synthesis of the title compound was performed in the same manner as in Example 670 using appropriate starting materials. 
         [1190]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.75-2.81 (2H, m), 2.95-3.02 (2H, m), 3.38 (3H, s), 3.69-3.73 (4H, m), 3.75-3.83 (1H, m), 4.09-4.16 (1H, m), 5.20 (2H, s), 6.78 (1H, brs), 6.96 (1H, dd, J=1.2 and 7.6 Hz), 7.08 (1H, dd, J=1.9 and 8.4 Hz), 7.11-7.18 (4H, m), 7.23 (1H, d, J=8.4 Hz), 8.50-8.53 (2H, m) 
       Example 672 
     7-({N-(3-Aminopyridin-2-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1191]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. Ivory powder 
       mp: 217-218° C. 
     Example 673 
     7-({N-(3-Aminopyridin-2-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1192]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 188-192° C. 
     Example 674 
     7-({N-(2-Diethoxymethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c ]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1193]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
       mp: 138-139° C. 
     Example 675 
     2-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde 
       [1194]    The synthesis of the title compound was performed in the same manner as in Example 621 using appropriate starting materials. 
       mp: 157-158° C. 
     Example 676 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1195]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1196]      1 H NMR (DMSO-d 6 ), δ ppm: 0.00 (2H, br), 0.21-0.23 (2H, m), 0.61 (3H, s), 0.75 (1H, br), 1.26 (3H, s), 2.35 (3H, s), 2.68 (2H, br), 3.24 (3H, s), 3.12-3.80 (6H, m), 3.90-4.20 (6H, m), 4.50 (2H, s), 6.41 (1H, s), 6.55 (1H, br), 7.20 (1H, br), 7.25-7.50 (3H, m), 7.60 (1H, br), 8.20 (1H, br), 8.48 (1H, s). 
       Example 677 
     5-Cyclopropyl-1-cyclopropylmethyl-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1197]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1198]      1 H NMR (DMSO-d 6 ), δ ppm: −0.09-0.05 (3H, m), 0.12-0.23 (2H, m), 0.35-0.46 (1H, m), 0.63-0.80 (2H, m), 0.72 (3H, s), 1.06-1.13 (1H, m), 1.33 (3H, s), 2.43 (3H, s), 2.81 (2H, br), 3.20 (1H, br), 3.34 (3H, s), 3.37-3.45 (2H, m), 3.80 (2H, br), 4.15-4.20 (3H, m), 4.67 (3H, br), 6.49 (1H, br), 6.66 (1H, br), 7.13-7.60 (4H, m), 7.77-7.80 (1H, m), 8.42 (1H, br), 8.63 (1H, br). 
       Example 678 
     7-({N-(3-Diethoxymethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c ]Pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1199]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
       mp: 112-114° C. 
     Example 679 
     3-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde 
       [1200]    The synthesis of the title compound was performed in the same manner as in Example 621 using appropriate starting materials. 
       mp: 79-84° C. 
     Example 680 
     1-Ethyl-7-({N-(2-hydroxymethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1201]    Sodium borohydride (47 mg) were added to a methanol solution (10 ml) of 2-({N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde (0.59 g) was stirred for 3 hours at 0° C. Water was added to the reaction mixture, followed by extraction by ethyl acetate. The organic layer was dried by anhydrous sodium sulfate, and condensed under reduced pressure. The residue was recrystallized from ethyl acetate-ether mixture to give the title compound (0.42 g) as a pale brown white powder. 
       mp: 159-161° C. 
     Example 681 
     1-Ethyl-3,3,5-trimethyl-7-{[4-(2-oxo-3,4-dihydro-2H-quinolin-1-yl methyl)benzylamino]-methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1202]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1203]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.76-2.81 (2H, m), 2.95-3.02 (2H, m), 3.41 (3H, s), 3.74-3.83 (5H, m), 4.10-4.18 (1H, m), 5.17 (2H, s), 6.85-6.90 (1H, m), 6.96-7.00 (1H, m), 7.07-7.13 (1H, m), 7.15-7.35 (8H, m) 
       Example 682 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-7-({N-(2-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1204]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1205]      1 H NMR (DMSO-d 6 ), δ ppm: 0.03-0.10 (2H, m), 0.25-0.29 (2H, m), 0.66 (3H, s), 0.77-0.85 (1H, m), 1.30 (3H, s), 2.38 (3H, s), 2.95-3.15 (2H, m), 3.07 (3H, s), 3.10-3.42 (4H, m), 3.30 (3H, s), 3.50-3.57 (1H, m), 3.87 (2H, br), 3.97-4.09 (1H, m), 4.33 (4H, br), 4.77 (2H, br), 6.48 (1H, s), 6.64 (1H, d, J=7.3 Hz), 7.47 (2H, br), 7.57-7.60 (1H, m), 7.79-7.82 (2H, m), 8.66-8.67 (2H, m). 
       Example 683 
     5-Cyclopropyl-1-cyclopropylmethyl-3,3-dimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1206]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1207]      1 H NMR (DMSO-d 6 ), δ ppm: −0.09-0.03 (3H, m), 0.15-0.27 (2H, m), 0.37-0.44 (1H, m), 0.72 (3H, s), 0.65-0.76 (2H, m), 1.06-1.10 (1H, m), 1.33 (3H, s), 2.43 (3H, br), 2.49 (3H, br), 2.79 (2H, br), 3.17-3.22 (1H, m), 3.38-3.49 (1H, m), 3.77 (2H, br), 3.81 (2H, br), 4.14 (2H, br), 4.16-4.22 (1H, m), 6.45 (1H, s), 6.62 (1H, d, J=7.0 Hz), 7.26 (1H, br), 7.36 (1H, br), 7.45-7.48 (2H, m), 7.68-7.72 (1H, m), 8.29 (1H, br), 8.56 (1H, br). 
       Example 684 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-morpholin-4-ylmethylbenzyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1208]    Morpholine (0.06 ml) and acetic acid (0.1 ml) were added to a 1,2-dichloroethane solution (7 ml) of 2-({N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)benzaldehyde (0.35 g), and the mixture was stirred for 30 minutes at room temperature. Sodium triacetoxy borohydride (0.20 g) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction liquid, followed by extraction by dichloromethane. The organic layer was dried by anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:hexane=3:2). The purified product was condensed under reduced pressure to give the title compound (0.30 g) as a white amorphous solid. 
         [1209]      1 H NMR (CDCl 3 ), d ppm: 0.78 (3H, s), 1.16 (3H, t, J=7.0 Hz), 1.51 (3H, s), 2.28-2.38 (4H, m), 2.43 (3H, d, J=1.0 Hz), 2.83 (2H, t, J=6.1 Hz), 3.32 (3H, s), 3.43 (2H, s), 3.56-3.88 (9H, m), 3.96-4.07 (2H, m), 4.07-4.18 (1H, m), 6.40 (1H, dd, J=0.64, 7.4 Hz), 6.48 (1H, d, J=0.88 Hz), 6.89 (1H, d, J=7.3 Hz), 7.08 (2H, d, J=0.96 Hz), 7.12-7.20 (3H, m), 7.21-7.26 (1H, m), 7.37 (1H, dd, J=2.1, 7.0 Hz). 
       Example 685 
     1-Ethyl-7-({N-(3-hydroxymethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1210]    The synthesis of the title compound was performed in the same manner as in Example 680 using appropriate starting materials. 
       mp: 170-172° C. 
     Example 686 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-morpholin-4-ylmethylbenzyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1211]      1 H NMR (CDCl 3 ) 0.77 (3H, s), 1.16 (3H, t, J=7.0 Hz), 1.51 (3H, s), 2.37-2.46 (4H, m), 2.43 (3H, d, J=0.96 Hz), 2.82 (2H, dt, J=2.3, 5.8 Hz), 3.31 (3H, s), 3.41 (2H, s), 3.59-3.82 (9H, m), 3.96-4.19 (3.H, m), 6.44 (1H, dd, J=0.70 7.4 Hz), 6.48 (1H, t, J=0.9 Hz), 6.97-7.09 (3H, m), 7.11-7.26 (5H, m). 
       Example 687 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(2-oxo-1-pyridin-2-ylmethyl-1,2,3,4-tetrahydro-quinolin-7-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1212]    The synthesis of the title compound was performed in the same manner as in Example 670 using appropriate starting materials. 
         [1213]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.75-2.81 (2H, m), 2.95-3.01 (2H, m), 3.39 (3H, s), 3.70-3.73 (4H, m), 3.74-3.84 (1H, m), 4.08-4.14 (1H, m), 5.30 (2H, s), 6.95 (1H, dd, J=1.3 and 7.6 Hz), 7.05 (1H, brs), 7.11-7.25 (6H, m), 7.60 (1H, dt, J=1.8 and 7.7 Hz), 8.50-8.55 (1H, m) 
       Example 688 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(2-oxo-1-pyridin-3-ylmethyl-1,2,3,4-tetrahydroquinolin-7-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1214]    The synthesis of the title compound was performed in the same manner as in Example 670 using appropriate starting materials. 
         [1215]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.75-2.80 (2H, m), 2.94-2.99 (2H, m), 3.39 (3H, s), 3.70-3.73 (4H, m), 3.75-3.84 (1H, m), 4.08-4.18 (1H, m), 5.22 (2H, s), 6.91 (1H, brs), 6.96 (1H, dd, J=1.2 and 7.6 Hz), 7.10-7.18 (3H, m), 7.20-7.24 (2H, m), 7.55 (1H, dt, J=2.2 and 7.8 Hz), 8.47 (1H, dd, J=1.6 and 4.8 Hz), 8.56 (1H, d, J=1.8 Hz) 
       Example 689 
     1-Ethyl-3,3,5-trimethyl-7-([N-methyl-N-[3-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)benzyl]amino]methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1216]    The synthesis of the title compound was performed in the same manner as in Example 616 using appropriate starting materials. 
         [1217]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.15-1.21 (3H, m), 1.53 (3H, s), 2.16 (3H, s), 2.76-2.81 (2H, m), 2.95-3.01 (2H, m), 3.40 (3H, s), 3.47-3.54 (4H, m), 3.75-3.82 (1H, m), 4.08-4.16 (1H, m), 5.18 (2H, s), 6.86 (1H, dd, J=0.8 and 8.1 Hz), 6.95 (1H, dt, J=1.0 and 7.4 Hz), 7.04-7.12 (2H, m), 7.15-7.30 (7H, m) 
       Example 690 
     1-Ethyl-3,3,5-trimethyl-7-({N-methyl-N-[4-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)-benzyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1218]    The synthesis of the title compound was performed in the same manner as in Example 616 using appropriate starting materials. 
         [1219]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.18 (3H, s), 2.76-2.81 (2H, m), 2.95-3.01 (2H, m), 3.41 (3H, s), 3.48-3.52 (4H, m), 3.75-3.82 (1H, m), 4.08-4.17 (1H, m), 5.17 (2H, s), 6.85-6.90 (1H, m), 6.95-7.00 (1H, m), 7.06-7.13 (1H, m), 7.15-7.33 (8H, m) 
       Example 691 
     7-({N-(2-Dimethylaminomethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1220]    To the 1,2-dichloroethan suspension (5 ml) of 3-((N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)methyl)-N-(2-(2-methyl-4-oxofuro[3,2-c]pyridin-5(4H)-yl)ethyl)amino)methyl)picolinaldehyde (205 mg), dimethylammonium chloride (59 mg) and triehylamine (0.10 ml) was added sodium triacetoxyborohydride (114 mg) at room temperature, and the mixture was stirred overnight. The mixture was concentrated under reduced pressure, and then the residue was purified by column-chromatography (methanol:ethyl acetate=1:9→50:50). The purified product was dissolved in ethyl acetate (ca. 5 mL) and then 4 M HCl/ethyl acetate was added to the mixture. The precipitate was collected and dried in vacuo to give the titled compound as light brown powder (114 mg). 
         [1221]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 (3H, s), 1.06 (3H, t, J=7.0 Hz), 1.34 (3H, s), 2.40 (3H, br), 2.89 (6H, s), 3.15-3.44 (2H, m), 3.34 (3H, s), 3.70-4.05 (10H, m), 6.55 (1H, s), 6.73 (1H, d, J=7.4 Hz), 7.20-8.00 (5H, m), 8.26 (1H, br), 8.64 (1H, br). 
       Example 692 
     1-Ethyl-3,3,5-trimethyl-7-({N-(2-methylaminomethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1222]    To a methanol solution (5 ml) of 3-({N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridine-2-carbaldehyde (243 mg) was added 9.8 M THF solution of methylamine (87 □l) and the mixture was stirred overnight at room temperature. NaBH 4  (16 mg) was added to the mixture, and then the mixture was stirred overnight. The resulting mixture was evaporated and the residue was purified by column chromatography (methanol:ethyl acetate=1:9-50:50). The purified product was dissolved in ethyl acetate (ca. 5 ml) and then 4 M HCl/ethyl acetate was added to the mixture. The precipitate was collected and dried in vacuo to give the titled compound as light brown powder (18 mg). 
         [1223]      1 H NMR (DMSO-d 6 ) δ ppm: 0.70 (3H, s), 1.06 (3H, t, J=7.0 Hz), 1.34 (3H, s), 2.40 (3H, br), 2.66 (3H, s), 3.05-3.45 (2H, m), 3.34 (3H, s), 3.70-4.05 (10H, m), 6.56 (1H, s), 6.74 (1H, d, J=7.4 Hz), 7.48 (3H, br), 7.64 (1H, d, J=6.5 Hz), 7.77 (1H, br), 8.23 (1H, br), 8.62 (1H, br), 9.32 (2H, br). 
       Example 693 
     7-({N-(2-Cyclopropylaminomethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1224]    The synthesis of the title compound was performed in the same manner as in Example 692 using appropriate starting materials. 
         [1225]      1 H NMR (DMSO-d 6 ), δ ppm: 0.72 (3H, s), 0.70-0.74 (2H, m), 0.98 (2H, br), 1.08 (3H, t, J=7.0 Hz), 1.35 (3H, s), 2.41 (3H, br), 2.75 (2H, br), 3.33 (3H, s), 3.60-3.90 (5H, m), 3.91-4.05 (1H, m), 4.20-4.70 (5H, m), 6.55 (1H, s), 6.73 (1H, d, J=7.3 Hz), 7.45 (3H, br), 7.59-7.61 (2H, m), 8.15 (1H, br), 8.59 (1H, br), 9.54 (2H, br). 
       Example 694 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-pyrrolidin-1-ylmethylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1226]    The synthesis of the title compound was performed in the same manner as in Example 691 using appropriate starting materials. 
         [1227]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 (3H, s), 1.06 (3H, t, J=7.0 Hz), 1.35 (3H, s), 2.00 (4H, br), 2.43 (3H, br), 2.76 (2H, br), 3.28 (7H, br), 3.75 (4H, br), 3.90-4.30 (2H, m), 4.55 (4H, br), 6.52 (1H, br), 6.70 (1H, br), 7.25 (2H, br), 7.32 (1H, br), 7.52 (2H, br), 7.69 (1H, br), 8.47 (1H, br), 10.3 (1H, br). 
       Example 695 
     1-Ethyl-7-({N-[2-(3-hydroxypyrrolidin-1-ylmethyl)pyridin-3-ylmethyl]-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione trihydrochloride 
       [1228]    The synthesis of the title compound was performed in the same manner as in Example 691 using appropriate starting materials. 
         [1229]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 (3H, s), 1.07 (3H, t, J=6.9 Hz), 1.35 (3H, s), 1.95 (1H, br), 2.19 (1H, br), 2.42 (3H, br), 2.75 (2H, br), 3.10-3.60 (9H, m), 3.75 (4H, br), 3.90-4.25 (3H, m), 4.47 (2H, br), 6.52 (1H, br), 6.70 (1H, br), 7.27 (3H, br), 7.53 (2H, br), 7.69 (1H, br), 8.49 (1H, br), 10.4 (1H, br). 
       Example 696 
     1-Ethyl-3,3,5-trimethyl-7-{[2-(2-oxo-3,4-dihydro-2H-quinolin-1-yl methyl)benzylamino]-methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1230]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1231]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.78-2.83 (2H, m), 2.99-3.04 (2H, m), 3.32 (3H, s), 3.74-3.81 (1H, m), 3.90-3.93 (4H, m), 4.08-4.14 (1H, m), 5.30-5.34 (2H, m), 6.82 (1H, dd, J=1.0 and 7.9 Hz), 6.91-7.03 (3H, m), 7.13-7.35 (7H, m) 
       Example 697 
     1-Ethyl-3,3,5-trimethyl-7-({N-(4-methylpyridin-3-ylmethyl)-N-[2-(2-oxo-2H-quinolin-1-yl)ethyl]amino}methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1232]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 120-121° C. 
     Example 698 
     7-({N-(2,6-Dimethylpyridin-3-ylmethyl)-N-[2-(2-oxo-2H-quinolin-1-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1233]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 159-160° C. 
     Example 699 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1234]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 174-175° C. 
     Example 700 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(4-methyl-7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1235]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 163-165° C. 
     Example 701 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyrimidin-5-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1236]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 166-167° C. 
     Example 702 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(4-methyl-7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1237]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 174-177° C. 
     Example 703 
     1-Ethyl-3,3,5-trimethyl-7-({N-methyl-N-[2-(2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)benzyl]amino}methyl)-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1238]    The synthesis of the title compound was performed in the same manner as in Example 616 using appropriate starting materials. 
         [0000]    White powder 
       mp: 125-127° C. 
     Example 704 
     1-Ethyl-7-({N-(6-hydroxymethylpyridin-3-ylmethyl)-N-[2-(1-oxo-1H-isoquinolin-2-yl)-ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1239]    The synthesis of the title&#39;compound was performed in the same manner as in Example 30 using 6-((tert-butyldimethylsilyloxy)methyl)nicotinaldehyde and 1-ethyl-3,3,5-trimethyl-7-((2-(1-oxoisoquinolin-2(1H)-yl)ethylamino)methyl)-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione, followed by deprotection of TBDMS group with tetrabutylammonium fluoride. 
         [1240]      1 H NMR (CDCl 3 ), δ ppm: 0.75 (3H, s), 1.13 (3H, t, J=7.1 Hz), 1.50 (3H, s), 2.85-2.88 (2H, m), 3.27 (3H, s), 3.62-3.75 (5H, m), 3.96-4.02 (1H, m), 4.13 (2H, t, J=7.2 Hz), 4.65 (2H, s), 6.46 (1H, d, J=7.3 Hz), 6.93 (1H, d, J=7.3 Hz), 6.96-6.99 (2H, m), 7.05 (1H, dd, J=1.8, 8.4 Hz), 7.13 (1H, d, J=1.6 Hz), 7.48-7.57 (3H, m), 7.66-7.71 (1H, m), 8.33 (1H, dd, J=0.6, 8.1 Hz), 8.41 (1H, d, J=1.5 Hz). 
       Example 705 
     1-Ethyl-3,3,5-trimethyl-7-(3-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(7-oxo-7H-thieno[2,3-c]pyridin-6-yl)ethyl]amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1241]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1242]      1 H NMR (DMSO-d 6 ), δ ppm: 0.71 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.33 (3H, s), 1.65-2.34 (2H, m), 2.52-2.92 (6H, m), 3.25-4.82 (12H, m), 6.60-6.92 (1H, m), 7.03-7.19 (1H, m), 7.19-7.31 (1H, m), 7.31-7.41 (2H, m), 7.41-7.90 (2H, m), 8.00-8.11 (1H, m), 8.12-8.60 (2H, m). 
       Example 706 
     1-Ethyl-3,3,5-trimethyl-7-(3-{N-(2-methylpyridin-3-ylmethyl)-N-[2-(4-oxo-4H-thieno[3,2-c]pyridin-5-yl)ethyl]amino}propyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1243]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1244]      1 H NMR (DMSO-d 6 , δ ppm: 0.71 (3H, s), 1.04 (3H, t, J=7.1 Hz), 1.32 (3H, s), 1.66-2.29 (2H, m), 2.55-2.71 (2H, m), 2.71-2.92 (4H, m), 2.96-4.81 (12H, m), 6.81-7.02 (2H, m), 7.02-7.41 (4H, m), 7.41-7.69 (1H, m), 7.41-7.90 (2H, m), 8.42-8.93 (1H, m). 
       Example 707 
     7-{[2-(2,6-Dimethylpyridin-3-yl)ethylamino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1245]    The synthesis of the title compound was performed in the same manner as in Example 590 using appropriate starting materials. 
         [1246]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.49 (3H, s), 2.51 (3H, s), 2.78-2.83 (2H, m), 2.85-2.89 (2H, m), 3.40 (3H, s), 3.74-3.84 (1H, m), 3.84 (2H, s), 4.09-4.19 (1H, m), 6.93 (1H, d, J=7.7 Hz), 7.17-7.19 (2H, m), 7.24 (1H, s), 7.32 (1H, d, J=7.7 Hz). 
       Example 708 
     7-{[N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1247]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1248]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.23 (3H, s), 3.42 (3H, s), 3.75-3.83 (8H, m), 4.09-4.20 (1H, m), 5.94 (1H, s), 7.20-7.28 (3H, m). 
       Example 709 
     1-Ethyl-7-{[N-(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1249]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1250]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.41 (3H, s), 3.42 (3H, s), 3.74-3.85 (1H, s), 3.85 (2H, s), 3.91 (2H, s), 4.10-4.67 (1H, m), 4.67 (2H, s), 7.22-7.28 (4H, m), 7.72-7.74 (1H, m), 8.49-8.51 (1H, m). 
       Example 710 
     1-Ethyl-3,3,5-trimethyl-7-{[N-(3-methyl-3H-imidazol-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1251]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1252]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.69 (3H, s), 3.75-3.84 (1H, m), 3.80 (2H, s), 3.83 (2H, s), 4.11-4.18 (1H, m), 6.92 (1H, s), 7.20-7.23 (2H, m), 7.25-7.28 (1H, m), 7.42 (1H, s). 
       Example 711 
     1-Ethyl-3,3,5-trimethyl-7-[(1-pyridin-3-ylethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1253]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1254]      1 H NMR (CDCl 3 ), δ ppm: 0.81-0.82 (3H, m), 1.17 (3H, t, J=7.1 Hz), 1.42-1.44 (3H, m), 1.53 (3H, s), 3.40-3.41 (3H, m), 3.62-3.70 (2H, m), 3.73-3.83 (1H, m), 3.85-3.91 (1H, m), 4.09-4.19 (1H, m), 7.14-7.19 (2H, m), 7.22-7.31 (2H, m), 7.70-7.74 (1H, m), 8.51-8.53 (1H, m), 8.58 (1H, d, J=2.0 Hz). 
       Example 712 
     7-{[(1,5-Dimethyl-1H-pyrazol-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1255]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1256]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.77 (6H, s), 2.26 (3H, s), 3.42 (3H, s), 3.74-3.85 (1H, m), 3.74 (3H, s), 3.77 (2H, s), 3.86 (2H, s), 5.96 (1H, s), 7.23-7.24 (3H, m). 
       Example 713 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-nitrobenzenesulfonamide 
       [1257]    Triethylamine (0.6 ml) was added to a dichloromethane solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-aminomethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.0 g). The mixture was cooled with ice. 2-Nitrobenzenesulphonyl chloride (0.80 g) was added, and the mixture was stirred at room temperature overnight. A saturated sodium bicarbonate solution was added to the reaction mixture, followed by extraction using dichloromethane. 
         [1258]    The organic layer was washed with water and saturated saline, dried with magnecium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:4). The purified product was condensed under reduced pressure, and the residue was recrystallized from the ethyl acetate-hexane mixture to give the title compound (1.38 g) as a white solid. 
         [1259]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 3.35 (3H, s), 3.72-3.83 (1H, m), 4.06-4.17 (1H, m), 4.35 (2H, d, J=6.4 Hz), 5.78 (1H, d, J=6.4 Hz), 7.16-7.23 (3H, m), 7.73-7.79 (2H, m), 7.86-7.91 (1H, m), 8.12-8.15 (1H, m) 
       Example 714 
     1-Ethyl-3,3,5-trimethyl-7-{[(5-methyloxazol-4-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1260]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1261]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.29 (3H, s), 3.42 (3H, s), 3.68 (2H, s), 3.72-3.86 (3H, m), 4.09-4.23 (1H, m), 7.20-7.30 (3H, m), 7.74 (1H, s). 
       Example 715 
     1-Ethyl-7-{[(6-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1262]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1263]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.49 (3H, s), 3.74-3.85 (1H, m), 3.83 (2H, s), 3.85 (2H, s), 4.10-4.20 (1H, m), 4.58 (2H, s), 7.23-7.37 (3H, m), 7.40 (1H, d, J=8.0 Hz), 7.71 (1H, dd, J=8.0, 2.1 Hz), 8.53 (1H, d, J=1.9 Hz). 
       Example 716 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methyl-1-oxypyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1264]    To a dichloromethane solution (10 ml) of 1-ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (2.0 g) was added m-chloroperbenzoic acid (mCPBA, 0.89 g) at 0° C. and the mixture was stirred overnight. The resulting mixture was charged on silica gel and purified by column chromatography (methanol/ethyl acetate 1:9, 1:1) to give the titled compound as white amorphous (0.46 g). 
         [1265]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.35 (3H, s), 2.44 (3H, d, J=1.0 Hz), 2.84 (2H, t, J=6.1 Hz), 3.35 (3H, s), 3.62 (2H, s), 3.69-3.83 (3H, m), 4.03-4.18 (3H, m), 6.41 (1H, dd, J=7.3, 0.7 Hz), 6.51 (1H, t, J=0.9 Hz), 6.85 (1H, d, J=7.3 Hz), 6.92-6.96 (1H, m), 7.09-7.11 (2H, m), 7.15-7.18 (1H, m), 7.21-7.22 (1H, m), 8.14 (1H, d, J=6.0 Hz). 
       Example 717 
     1-Ethyl-3,3,5-trimethyl-7-{[(3-methyl-pyridin-2-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1266]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1267]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.28 (3H, s), 3.42 (3H, s), 3.73-3.87 (1H, m), 3.91 (2H, s), 3.93 (2H, s), 4.08-4.23 (1H, m), 7.11 (1H, dd, J=4.8, 7.6 Hz), 7.22-7.34 (3H, m), 7.41-7.47 (1H, m), 8.41 (1H, dd, J=1.1, 4.8 Hz). 
       Example 718 
     1-Ethyl-3,3,5-trimethyl-7-{[1-(2-methylpyridin-3-yl)ethylamino]-methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1268]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1269]      1 H NMR (CDCl 3 ), δ ppm: 0.82-0.83 (3H, m), 1.15-1.89 (3H, m), 1.35-1.37 (3H, m), 1.53 (3H, s), 2.52 (3H, d, J=8.0 Hz), 3.39-3.40 (3H, m), 3.66 (2H, s), 3.73-3.82 (1H, m), 4.05-4.20 (2H, m), 7.18-7.20 (3H, m), 7.23-7.24 (1H, m), 7.85 (1H, dd, J=7.8, 1.6 Hz), 8.40 (1H, d, J=4.7 Hz). 
       Example 719 
     7-{[(2-Ethoxymethylpyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1270]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1271]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.17 (6H, t, J=7.0 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.57 (2H, q, J=7.0 Hz), 3.74-3.83 (1H, m), 3.84 (2H, s), 3.92 (2H, s), 4.09-4.20 (1H, m), 4.71 (2H, s), 7.22-7.28 (4H, m), 7.71 (1H, dd, J=7.7, 1.6 Hz), 8.49 (1H, dd, J=4.8, 1.6 Hz). 
       Example 720 
     1-Ethyl-7-{[1-(2-methoxymethylpyridin-3-yl)ethylamino]methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1272]    The synthesis of the title compound was performed in the same manner as in Example 584 using appropriate starting materials. 
         [1273]      1 H NMR (CDCl 3 ), δ ppm: δ 0.82-0.83 (3H, m), 1.16 (3H, t, J=6.9 Hz), 1.40 (3H, d, J=6.4 Hz), 1.52 (3H, s), 3.37-3.40 (6H, m), 3.60 (1H, d, J=13.6 Hz), 3.68 (1H, d, J=13.6 Hz), 3.72-3.82 (1H, m), 4.09-4.20 (1H, m), 4.23-4.30 (1H, m), 4.57-4.66 (2H, m), 7.15-7.19 (2H, m), 7.22-7.26 (1H, m), 7.27-7.32 (1H, m), 7.96-7.98 (1H, m), 8.49 (1H, dd, J=4.7, 1.7 Hz). 
       Example 721 
     1-Ethyl-3,3,5-trimethyl-7-{[2-(1-oxo-1H-isoquinolin-2-yl)ethylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1274]    2-(2-Aminoethyl)-2H-isoquinolin-1-one (1.0 g) was added to a methanol solution (15 ml) of 1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbaldehyde (1.46 g). The mixture was stirred for 0.5 hours at room temperature. Sodium borohydride (0.23 g) was added to the mixture, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using dichloromethane. The organic layer was washed with water and saturated saline, dried with magnesium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=9:1→8:2). The purified product was condensed under reduced pressure to give the title compound (1.92 g) as a white solid. 
         [1275]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.51 (3H, s), 3.01-3.11 (2H, m), 3.31 (3H, s), 3.71-3.81 (1H, m), 3.84 (2H, s), 4.04-4.15 (1H, m), 4.16 (2H, t, J=6.0 Hz), 6.51 (1H, d, J=7.3 Hz), 7.12-7.18 (4H, m), 7.48-7.56 (2H, m), 7.63-7.70 (1H, m), 8.41 (1H, d, J=8.1 Hz) 
       Example 722 
     1-Ethyl-3,3,5-trimethyl-7-(quinolin-5-ylaminomethyl)-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1276]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1277]      1 H NMR (CDCl 3 ), δ ppm: 0.86 (3H, s), 1.21 (3H, t, J=7.1 Hz), 1.54 (3H, s), 3.38 (3H, s), 3.76-3.89 (1H, m), 4.09-4.22 (1H, m), 4.56 (2H, d, J=4.4 Hz), 4.70-4.88 (1H, m), 6.62 (1H, dd, J=2.6, 6.1 Hz), 7.28-7.35 (3H, m), 7.38 (1H, dd, J=4.2, 8.6 Hz), 7.50-7.58 (2H, m), 8.23 (1H, dd, J=1.4, 8.6 Hz), 8.92 (1H, dd, J=1.6, 4.2 Hz). 
       Example 723 
     7-{[(4-Chloro-pyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trim ethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1278]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1279]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.72-3.90 (3H, m), 3.96 (2H, s), 4.08-4.22 (1H, m), 7.22-7.27 (3H, m), 7.33 (1H, d, J=5.3 Hz), 8.44 (1H, d, J=5.3 Hz), 8.60 (1H, s). 
       Example 724 
     7-{[(2-Chloropyridin-3-ylmethyl)amino]methyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1280]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1281]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.74-3.86 (1H, m), 3.86 (2H, s), 3.93 (2H, s), 4.08-4.23 (1H, m), 7.21-7.31 (4H, m), 7.80 (1H, dd, J=1.9, 7.5 Hz), 8.32 (1H, dd, J=1.9, 4.8 Hz). 
       Example 725 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-pyridin-3-ylmethyl)carbamic acid tert-butyl ester 
       [1282]    To a THF solution (15 ml) of 1-ethyl-3,3,5-trimethyl-7-(((2-methylpyridin-3-yl)methylamino)methyl)-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione (0.92 g) was added di-tert-butyl dicarbonate (0.58 g) at room temperature, the mixture was stirred overnight. The resulting mixture was concentrated and then purified by column chromatography (ethyl acetate/hexanes 1:4→1:1→7:3) to give the titled compound as colorless oil (0.88 g). 
         [1283]      1 H NMR (CDCl 3 ), □□ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.0 Hz), 1.49 (9H, s), 1.53 (3H, s), 2.45 (3H, s), 3.36 (3H, s), 3.75-3.84 (1H, m), 4.09-4.18 (1H, s), 4.43 (4H, br), 6.99-7.12 (3H, m), 7.23-7.25 (1H, m), 7.35-7.38 (1H, m), 8.39-8.41 (1H, m). 
       Example 726 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(4-methylthiazol-5-ylmethyl)carbamic acid tert-butyl ester 
       [1284]    The synthesis of the title compound was performed in the same manner as in Example 725 using appropriate starting materials. 
         [1285]      1 HNMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.45-1.55 (12H, m), 2.34 (3H, s), 3.36 (3H, s), 3.76-3.84 (1H, m), 4.09-4.16 (1H, m), 4.42 (2H, s), 4.54 (2H, s), 7.00-7.09 (2H, m), 7.24-7.27 (1H, m), 8.62 (1H, s). 
       Example 727 
     N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl) carbamic acid tert-butyl ester 
       [1286]    The synthesis of the title compound was performed in the same manner as in Example 725 using appropriate starting materials. 
         [1287]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.49 (9H, br), 1.54 (3H, s), 2.21 (3H, s), 3.38 (3H, s), 3.72 (3H, br), 3.75-3.85 (1H, m), 4.09-4.18 (1H, m), 4.35 (2H, br), 4.44 (2H, br), 5.88 (1H, s), 7.00-7.05 (2H, m), 7.24-7.27 (1H, m). 
       Example 728 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-1-oxypyridin-3-ylmethyl)carbamic acid tert-butyl ester 
       [1288]    The synthesis of the title compound was performed in the same manner as in Example 716 using appropriate starting materials. 
         [1289]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.20 (3H, t, J=7.0 Hz), 1.49 (9H, s), 1.54 (3H, s), 2.45 (3H, s), 3.38 (3H, s), 3.76-3.86 (1H, m), 4.08-4.16 (1H, m), 4.43 (4H, br), 6.99-7.12 (4H, m), 7.25-7.29 (1H, m), 8.21-8.23 (1H, m). 
       Example 729 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-hydroxymethylpyridin-3-ylmethyl) carbamic acid tert-butyl ester 
       [1290]    The synthesis of the title compound was performed in the same manner as in Example 666 using appropriate starting materials. 
         [1291]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.13 (3H, t, J=7.1 Hz), 1.49 (9H, br), 1.53 (3H, s), 3.36 (3H, s), 3.75-3.84 (1H, m), 4.07-4.18 (1H, m), 4.40 (4H, br), 4.62 (2H, s), 7.00-7.08 (2H, m), 7.24-7.27 (2H, m), 7.47-7.49 (1H, m), 8.47-8.49 (1H, m). 
       Example 730 
     1-Ethyl-3,3,5-trimethyl-7-{[2-(7-oxo-7H-furo[2,3-c]pyridin-6-yl)ethylamino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1292]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 3.00-3.10 (2H, m), 3.34 (3H, s), 3.72-3.81 (1H, m), 3.84 (2H, s), 4.08-4.17 (1H, m), 4.21 (2H, t, J=6.0 Hz), 6.47 (1H, d, J=7.0 Hz), 6.67 (1H, d, J=2.0 Hz), 7.13-7.22 (4H, m), 7.74 (1H, d, J=2.0 Hz) 
       Example 731 
     1-Ethyl-7-{[(2-hydroxymethylpyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1293]    To a ethanol solution (20 ml) of tert-butyl (1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)methyl((2-(hydroxymethyl)pyridin-3-yl)methyl)carbamate (0.82 g) was added 5 M HCl and the mixture was stirred at 50° C. for 7 hours. The resulting mixture was concentrated and then 5 M NaOH was added thereto. Organic materials were extracted with ethyl acetate twice and then dried over MgSO 4 . After evaporation, the residue was purified by column chromatography (methanol/ethyl acetate 1:9→1:1) to give the titled compound as pale yellow oil (0.37 g). 
         [1294]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.0 Hz), 1.53 (3H, s), 3.42 (3H, s), 3.74-3.90 (5H, m), 4.09-4.19 (1H, m), 4.80 (2H, s), 7.20-7.29 (4H, m), 7.64-7.67 (1H, m), 8.49-8.51 (1H, m). 
       Example 732 
     1-Ethyl-7-{[(5-methoxymethyl-2-methyl-2H-pyrazol-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-d lone 
       [1295]    The synthesis of the title compound was performed in the same manner as in Example 3 using appropriate starting materials. 
         [1296]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3, t, J=7.0 Hz), 1.53 (3H, s), 3.40 (3H, s), 3.42 (3H, s), 3.77-3.87 (5H, m), 4.11-1.18 (1H, m), 4.41 (2H, s), 6.18 (1H, s), 7.21-7.28 (3H, m). 
       Example 733 
     1-Isobutyl-3,3-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1297]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1298]      1 H NMR (CDCl 3 ), δ ppm: 0.75 (3H, s), 0.77 (3H, s), 0.98 (3H, br), 1.53 (3H, br), 1.76-1.84 (1H, m), 2.56 (3H, s), 3.37-3.42 (1H, m), 3.82 (2H, s), 3.85 (2H, s), 4.34-4.40 (1H, m), 7.00-7.02 (1H, m), 7.10-7.14 (1H, m), 7.20-7.23 (1H, m), 7.24-7.27 (1H, m), 7.62 (1H, br), 7.62-7.64 (1H, m), 8.41 (1H, dd, J=4.9, 1.7 Hz). 
       Example 734 
     1-Isobutyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1299]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1300]      1 H NMR (CDCl 3 ), δ ppm: 0.74 (3H, s), 0.76 (3H, s), 0.98 (3H, br), 1.53 (3H, br), 1.74-1.85 (1H, m), 3.39-3.42 (1H, m), 3.40 (3H, s), 3.82 (2H, s), 3.90 (2H, s), 4.34-4.39 (1H, m), 7.01-7.02 (1H, m), 7.18-7.21 (1H, m), 7.23-7.27 (2H, m), 7.68 (1H, br), 7.74 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 735 
     1-(2-Methoxyethyl)-3,3-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1301]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1302]      1 H NMR (CDCl 3 ), δ ppm: 1.01 (3H, br), 1.53 (3H, br), 2.56 (3H, s), 3.34 (3H, s), 3.49 (1H, br), 3.60 (1H, br), 3.81 (2H, s), 3.84 (2H, s), 3.98 (1H, br), 4.11 (1H, br), 7.00 (1H, d, J=1.8 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.22 (1H, dd, J=8.4, 1.8 Hz), 7.58 (1H, d, J=8.4 Hz), 7.64 (1H, dd, J=7.6, 1.5 Hz), 7.92 (1H, br), 8.41 (1H, dd, J=4.9, 1.5 Hz). 
       Example 736 
     1-(2-Methoxyethyl)-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1303]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1304]      1 H NMR (CDCl 3 ), δ ppm: 1.01 (3H, br), 1.53 (3H, br), 3.34 (3H, s), 3.41 (3H, s), 3.59 (1H, br), 3.72 (1H, br), 3.81 (2H, s), 3.89 (2H, s), 3.98 (1H, br), 4.10 (1H, br), 4.67 (2H, s), 6.98-7.00 (1H, m), 7.21 (1H, dd, J=8.4, 1.9 Hz), 7.24-7.27 (1H, m), 7.57 (1H, d, J=8.4 Hz), 7.66 (1H, br), 7.73 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 737 
     1-Cyclopropylmethyl-3,3-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1305]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1306]      1 H NMR (CDCl 3 ), δ ppm: 0.18 (2H, br), 0.41 (2H, d, J=8.0 Hz), 0.96-1.07 (4H, m), 1.54 (3H, br), 3.65 (1H, br), 3.82 (2H, s), 3.85 (2H, s), 4.11 (1H, br), 7.03 (1H, d, J=1.8 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.21 (1H, dd, J=8.4, 1.8 Hz), 7.32 (1H, d, J=8.4 Hz), 7.63 (1H, dd, J=7.6, 1.6 Hz), 7.84 (1H, br), 8.41 (1H, dd. J=4.9, 1.6 Hz). 
       Example 738 
     1-Cyclopropylmethyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1307]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1308]      1 H NMR (CDCl 3 ), δ ppm: 0.19 (2H, br), 0.40 (2H, d, J=8.1 Hz), 0.97-1.07 (4H, m), 1.54 (3H, br), 3.41 (3H, s), 3.66 (1H, br), 3.82 (2H, s), 3.90 (2H, s), 4.10 (1H, br), 4.67 (2H, s), 7.04 (1H, d, J=1.8 Hz), 7.20 (1H, dd, J=8.4, 1.8 Hz), 7.23-7.26 (1H, m), 7.32 (1H, d, J=8.4 Hz), 7.74 (1H, dd, J=7.7, 1.6 Hz), 8.07 (1H, br), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 739 
     1-Cyclopropyl-3,3-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1309]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1310]      1 H NMR (CDCl 3 ), δ ppm: 0.40 (2H, br), 1.00 (2H, br), 1.54 (6H, br), 2.56 (3H, s), 3.16-3.22 (1H, m), 3.82 (2H, s), 3.85 (2H, s), 6.99 (1H, br), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.23 (1H, dd, J=8.4, 1.9 Hz), 7.34 (1H, d, J=8.4 Hz), 7.64 (1H, dd, J=7.6, 1.6 Hz), 8.13 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 740 
     1-Cyclopropyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1311]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1312]      1 H NMR (CDCl 3 ), δ ppm: 0.40 (2H, br), 1.00 (2H, br), 1.54 (6H, br), 3.16-3.21 (1H, m), 3.41 (3H, s), 3.82 (2H, s), 3.90 (2H, s), 4.67 (2H, s), 6.96 (1H, br), 7.21 (1H, dd, J=8.4, 1.9 Hz), 7.24-7.26 (1H, m), 7.34 (1H, d, J=8.4 Hz), 7.60 (1H, br), 7.74 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 741 
     N-[3-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide 
       [1313]    Tribuylphosphine (1.2 ml) and 1,1′-(azodicarbonyl)dipiperidine (1.17 g) were added to a toluene solution (100 ml) of 2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)-ethyl]-benzenesulfonamide (1.39 g), and 1-ethyl-7-(3-hydroxy-propyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione (0.94 g). The mixture was stirred overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water and saturated saline, dried with magnesium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1→1:0). The purified product was condensed under reduced pressure to produce the title compound (0.54 g) as a white amorphous. 
         [1314]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.91-2.01 (2H, m), 2.61 (2H, t, J=7.7 Hz), 3.31-3.51 (2H, m), 3.40 (3H, s), 3.70 (2H, t, J=6.7 Hz), 3.72-3.81 (1H, m), 4.09-4.17 (1H, m), 4.22 (2H, t, J=6.7 Hz), 6.45 (1H, d, J=7.3 Hz), 6.94 (1H, dd, J=8.4 and 1.9 Hz), 7.02 (1H, d, J=1.9 Hz), 7.12-7.16 (2H, m), 7.46-7.66 (6H, m), 7.90-7.94 (1H, m), 8.34 (1H, d, J=7.5 Hz) 
       Example 742 
     1-Ethyl-3,3,5-trimethyl-7-{3-[2-(1-oxo-1H-isoquinolin-2-yl)ethylamino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1315]    Lithium hydroxide (3.2 g), and thioglycolic acid (2.4 ml) were added to a DMF solution (27.4 ml) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)propyl]-2-nitro-N-[2-(1-oxo-1H-isoquinolin-2-yl)ethyl]benzenesulfonamide (4.56 g). The mixture was stirred at room temperature for 1 hour. The reaction mixture was condensed under reduced pressure. Water was added to the residue, followed by extraction using dichloromethane. The organic layer was washed with water and saturated saline, dried with magnesium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed under reduced pressure to produce the title compound (2.24 g) as a yellow oil. 
         [1316]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.77-1.88 (2H, m), 2.64-2.72 (4H, m), 3.04 (2H, t, J=6.3 Hz), 3.38 (3H, s), 3.69-3.80 (1H, m), 4.08-4.17 (3H, m), 6.51 (1H, d, J=7.3 Hz), 7.00-7.03 (2H, m), 7.11-7.17 (2H, m), 7.46-7.53 (2H, m), 7.61-7.66 (1H, m), 8.42 (1H, dd, J=8.0 and 0.6 Hz) 
       Example 743 
     1-Cyclopropyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1317]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1318]      1 H NMR (CDCl 3 ), δ ppm: 0.12-0.19 (1H, m), 0.60-0.67 (1H, m), 0.75-0.83 (1H, m), 0.85 (3H, s), 1.24-1.28 (1H, m), 1.52 (3H, s), 3.15-3.21 (1H, m), 3.39 (3H, s), 3.40 (3H, s), 3.84 (2H, s), 3.91 (2H, s), 4.67 (2H, s), 7.19-7.20 (1H, m), 7.22-7.29 (2H, m), 7.33 (1H, d, J=4.3 Hz), 7.73 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 744 
     1-Isobutyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1319]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1320]      1 H NMR (CDCl 3 ), δ ppm: 0.70 (3H, d, J=6.7 Hz), 0.75 (3H, d, J=6.7 Hz), 0.81 (3H, s), 1.53 (3H, s), 1.75-1.86 (1H, m), 3.31 (1H, dd, J=13.6, 6.4 Hz), 3.85 (2H, s), 3.91 (2H, s), 4.37 (1H, dd, J=13.6, 8.6 Hz), 4.67 (2H, s), 7.23-7.26 (4H, m), 7.72 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 745 
     1-(2-Methoxyethyl)-3,3,5-trimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1321]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1322]      1 H NMR (CDCl 3 ), δ ppm: 0.85 (3H, s), 1.53 (3H, s), 2.56 (3H, s), 3.29 (3H, s), 3.41 (3H, s), 3.53-3.58 (1H, m), 3.69 (1H, ddd, J=10.3, 7.1, 4.4 Hz), 3.82 (2H, s), 3.87 (2H, s), 3.97 (1H, ddd, J=14.1, 5.2, 4.6 Hz), 4.07-4.15 (1H, m), 7.13 (1H, dd, J=7.6, 4.9 Hz), 7.23-7.26 (2H, m), 7.50 (1H, d, J=8.2 Hz), 7.63 (1H, dd, J=7.6, 1.6 Hz), 8.42 (1H, dd, J=4.8, 1.6 Hz). 
       Example 746 
     1-Isobutyl-3,3-dimethyl-8-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1323]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1324]      1 H NMR (CDCl 3 ), δ ppm: 0.76 (6H, d, J=6.7 Hz), 0.98 (3H, s), 1.53 (3H, s), 1.78-1.89 (1H, m), 2.55 (3H, s), 3.41 (1H, dd, J=13.8, 6.5 Hz), 3.80 (2H, s), 3.87 (2H, s), 4.37 (1H, dd, J=13.8, 8.3 Hz), 6.97 (1H, d, J=8.1 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.19 (1H, dd, J=8.1, 1.7 Hz), 7.32 (1H, d, J=1.7 Hz), 7.62 (1H, dd, J=7.6, 1.6 Hz), 7.70 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 747 
     1-Isobutyl-8-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1325]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1326]      1 H NMR (CDCl 3 ), δ ppm: 0.76 (6H, d, J=6.7 Hz), 0.98 (3H, s), 1.53 (3H, s), 1.78-1.89 (1H, m), 3.39-3.46 (1H, m), 3.40 (3H, s), 3.83 (2H, s), 3.88 (2H, s), 4.33-4.42 (1H, m), 4.66 (2H, s), 6.97 (1H, d, J=8.1 Hz), 7.18 (1H, dd, J=8.1, 1.7 Hz), 7.23-7.26 (1H, m), 7.31 (1H, d, J=1.7 Hz), 7.72 (1H, dd, J=7.6, 1.6 Hz), 7.73 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 748 
     1-Cyclopropylmethyl-3,3-dimethyl-8-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1327]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1328]      1 H NMR (CDCl 3 ), δ ppm: 0.18 (2H, br), 0.41 (2H, d, J=7.9 Hz), 0.95-1.08 (4H, m), 1.54 (3H, br), 2.55 (3H, s), 3.70 (1H, br), 3.80 (2H, s), 3.87 (2H, s), 4.14 (1H, br), 6.97 (1H, d, J=8.1 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.19 (1H, dd, J=8.1, 1.6 Hz), 7.39 (1H, d, J=1.6 Hz), 7.62 (1H, dd, J=7.6, 1.6 Hz), 7.74 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 749 
     1-Cyclopropylmethyl-8-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1329]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1330]      1 H NMR (CDCl 3 ), δ ppm: 0.18 (2H, br), 0.41 (2H, d, J=7.9 Hz), 0.95-1.08 (4H, m), 1.54 (3H, br), 3.40 (3H, s), 3.71 (1H, br), 3.84 (2H, s), 3.89 (2H, s), 4.10 (1H, br), 4.66 (2H, s), 6.97 (1H, d, J=8.1 Hz), 7.18 (1H, dd, J=8.1, 1.6 Hz), 7.23-7.26 (1H, m), 7.37 (1H, d, J=1.6 Hz), 7.72 (1H, dd, J=7.7, 1.6 Hz), 7.83 (1H, br), 8.41 (1H, dd, J=4.8, 1.6 Hz). 
       Example 750 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methoxymethylpyridin-3-ylmethyl) carbamic acid tert-butyl ester 
       [1331]    N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-1-oxypyridin-3-ylmethyl) carbamic acid tert-butyl ester (188 mg) was dissolved in DMF (20 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 19.7 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (0.028 ml) was added thereto, and the mixture was stirred at 0° C. for 0.5 hours. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (162 mg) as a colorless oil. 
         [1332]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.48 (9H, bs), 1.53 (3H, s), 3.33 (3H, s), 3.36 (3H, s), 3.74-3.84 (1H, m), 4.08-4.18 (1H, m), 4.30-4.50 (2H, m), 4.52-4.72 (4H, m), 7.02-7.15 (2H, m), 7.20-7.25 (2H, m), 7.46-7.57 (1H, m), 8.46 (1H, dd, J=1.5 and 4.8 Hz) 
       Example 751 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-6-oxo-1,6-dihydropyridin-3-ylmethyl)carbamic acid tert-butyl ester 
       [1333]    N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-1-oxypyridin-3-ylmethyl)carbamic acid tert-butyl ester (2.35 g) was dissolved in acetic anhydride (20 ml). The reaction mixture was stirred at 100° C. for 2 h. The resulting mixture was evaporated, and dissolved in MeOH (15 ml). Potassium carbonate (6.8 g) was added to the mixture, and the reaction mixture was stirred 2 h at room temperature. Water was added to the resulting mixture and then the mixture was extracted with ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (536 mg) as a pale yellow amorphous. 
         [1334]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.49 (9H, s), 1.52 (3H, s), 2.37 (3H, s), 3.37 (3H, s), 3.77-3.83 (1H, m), 4.09-4.15 (1H, m), 4.30-4.52 (4H, m), 7.00-7.08 (2H, m), 7.09-7.15 (1H, m), 7.25-7.30 (1H, m), 8.07 (1H, d, J=2.6 Hz) 
       Example 752 
     1-Ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-yl-ethylamino)propyl]-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1335]    The synthesis of the title compound was performed in the same manner as in Example 742 using appropriate starting materials. 
         [1336]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.53 (3H, s), 1.78-1.85 (2H, m), 2.63-2.72 (4H, m), 2.79-2.83 (2H, m), 2.86-2.92 (2H, m), 3.40 (3H, s), 3.73-3.81 (1H, m), 4.09-4.18 (1H, m), 7.01-7.06 (2H, m), 7.19-7.23 (2H, m), 7.52-7.55 (1H, m), 8.47-8.49 (2H, m) 
       Example 753 
     1-Ethyl-3,3,5-trimethyl-7-[(3-[2-(7-oxo-7H-furo[2,3-c]pyridin-6-yl)ethylamino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1337]    The synthesis of the title compound was performed in the same manner as in Example 742 using appropriate starting materials. 
         [1338]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.73-1.84 (2H, m), 2.60-2.71 (4H, m), 3.03 (2H, t, J=6.2 Hz), 3.39 (3H, s), 3.73-3.81 (1H, m), 4.09-4.18 (1H, m), 4.17 (2H, t, J=6.2 Hz), 6.47 (1H, d, J=7.0 Hz), 6.66 (1H, d, J=2.0 Hz), 6.98-7.05 (2H, m), 7.14-7.20 (2H, m), 7.74 (1H, d, J=2.0 Hz) 
       Example 754 
     Acetic acid 3-{[N-tert-butoxycarbonyl-N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)amino]methyl}pyridin-2-ylmethyl ester 
       [1339]    The synthesis of the title compound was performed in the same manner as in Example 751 using appropriate starting materials. 
         [1340]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.19 (3H, t, J=7.1 Hz), 1.48 (9H, br), 1.57 (3H, s), 2.08 (3H, s), 3.36 (3H, s), 3.75-3.84 (1H, m), 4.09-4.18 (1H, m), 4.41 (2H, br), 4.57 (2H, br), 5.15 (2H, s), 7.03-7.12 (2H, m), 7.22-7.26 (2H, m), 7.47-7.50 (1H, m), 8.53 (1H, dd, J=4.8, 1.6 Hz). 
       Example 755 
     Acetic acid 3-{[(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benz o[b][1,4]diazepin-7-ylmethyl)amino]methyl}pyridin-2-ylmethyl ester 
       [1341]    The synthesis of the title compound was performed in the same manner as in Example 731 using appropriate starting materials. 
         [1342]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.11 (3H, s), 3.41 (3H, s), 3.74-3.82 (1H, m), 3.86 (2H, s), 3.90 (2H, s), 4.09-4.20 (1H, m), 5.33 (2H, s), 7.23-7.27 (4H, m), 7.72 (1H, d, J=7.7 Hz), 8.52-8.54 (1H, m). 
       Example 756 
     1-Ethyl-3,3,5-trimethyl-7-{3-[2-(4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethylamino]propyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1343]    The synthesis of the title compound was performed in the same manner as in Example 742 using appropriate starting materials. 
         [1344]      1 H NMR (CDCl 3 ), δ ppm: 0.81 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 1.76-1.83 (2H, m), 2.63-2.70 (4H, m), 3.01 (2H, t, J=6.2 Hz), 3.39 (3H, s), 3.72-3.81 (1H, m), 4.09-4.18 (3H, m), 6.54 (1H, dd, J=7.4 and 0.8 Hz), 6.96-7.04 (3H, m), 7.19 (1H, d, J=8.6 Hz), 7.23 (1H, d, J=7.4 Hz), 7.49 (1H, d, J=2.1 Hz), 
       Example 757 
     N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(6-methoxy-2-methylpyridin-3-ylmethyl)carbamic acid tert-butyl ester 
       [1345]    N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2, 3, 4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-(2-methyl-6-oxo-1,6-dihydropyridin-3-ylmethyl) carbamic acid tert-butyl ester (536 mg) was dissolved in DMF (20 ml), and was cooled to 0° C. in ice water bath. Sodium hydride (60% in oil, 56.1 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for 0.5 hours. Methyl iodide (0.081 ml) was added thereto, and the mixture was stirred at 0° C. for 0.5 hours. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (550 mg) as a yellow oil. 
         [1346]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.50 (9H, s), 1.53 (3H, s), 2.37 (3H, s), 3.36 (3H, s), 3.75-3.85 (4H, m), 4.09-4.20 (1H, m), 4.30-4.50 (4H, m), 6.85-6.98 (1H, m), 7.00-7.12 (2H, m), 7.23-7.28 (1H, m), 8.08 (1H, d, J=2.8 Hz) 
       Example 758 
     1-Ethyl-7-{[(6-methoxy-2-methyl-pyridin-3-ylmethyl)amino]methyl}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1347]    The synthesis of the title compound was performed in the same manner as in Example 670 using appropriate starting materials. 
         [1348]      1 H NMR (CDCl 3 ), δ ppm: 0.83 (3H, s), 1.18 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.47 (3H, s), 3.42 (3H, s), 3.78-3.83 (3H, m), 3.85 (3H, s), 3.88 (2H, s), 4.10-4.17 (1H, m), 7.20-7.30 (4H, m), 8.10 (1H, d, J=2.9 Hz) 
       Example 759 
     1,3,3-Trimethyl-8-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1349]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1350]      1 H NMR (CDCl 3 ), δ ppm: 1.08 (3H, br), 1.63 (3H, br), 2.56 (3H, s), 3.47 (3H, s), 3.81 (2H, s), 3.87 (2H, s), 6.97 (1H, d, J=8.1 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.19 (1H, dd, J=8.1, 1.7 Hz), 7.24-7.26 (1H, m), 7.62 (1H, dd, J=7.6, 1.6 Hz), 7.98 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 760 
     1-Ethyl-3,3-dimethyl-8-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1351]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1352]      1 H NMR (CDCl 3 ), δ ppm: 1.00 (3H, br), 1.26 (3H, t, J=7.1 Hz), 1.55 (3H, br), 2.56 (3H, s), 3.81 (2H, s), 3.87 (2H, s), 3.93 (1H, br), 4.09 (1H, br), 6.93-6.97 (1H, m), 7.12 (1H, dd, J=7.5, 4.9 Hz), 7.19 (1H, dd, J=8.2, 1.8 Hz), 7.24-7.26 (1H, m), 7.35 (1H, br), 7.63 (1H, dd, J=3.5, 1.5 Hz), 8.41 (1H, dd, J=4.8, 1.5 Hz). 
       Example 761 
     1,3,3-Trimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1353]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1354]      1 H NMR (CDCl 3 ), δ ppm: 1.05 (3H, br), 1.55 (3H, br), 2.56 (3H, s), 3.46 (3H, s), 3.82 (2H, s), 3.85 (2H, s), 7.03 (1H, br), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.20-7.23 (2H, m), 7.63 (1H, dd, J=7.6, 1.6 Hz), 8.03 (1H, br), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 762 
     1-Ethyl-3,3-dimethyl-7-{[(2-methylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1355]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1356]      1 H NMR (CDCl 3 ), δ ppm: 1.00 (3H, br), 1.22 (3H, t, J=7.1 Hz), 1.53 (3H, br), 2.56 (3H, s), 3.82 (2H, s), 3.85 (2H, s), 3.92 (1H, br), 4.12 (1H, br), 7.02 (1H, d, J=1.6 Hz), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.22 (1H, dd, J=8.4, 1.8 Hz), 7.29, (1H, d, J=8.4 Hz), 7.63 (1H, dd, J=7.6, 1.5 Hz), 7.85 (1H, br), 8.41 (1H, dd, J=4.9, 1.5 Hz). 
       Example 763 
     1-Ethyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1357]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1358]      1 H NMR (CDCl 3 ), δ ppm: 1.00 (3H, br), 1.22 (3H, t, J=7.1 Hz), 1.53 (3H, br), 3.41 (3H, s), 3.82 (2H, s), 3.90 (2H, s), 3.92 (1H, br), 4.08 (1H, br), 4.67 (2H, s), 7.01 (1H, d, J=1.5 Hz), 7.21 (1H, dd, J=8.4, 1.9 Hz), 7.23-7.29 (2H, m), 7.74 (1H, dd, J=7.7, 1.6 Hz), 7.79 (1H, br), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 764 
     8-{[(2-Methoxymethyl-pyridin-3-ylmethyl)amino]methyl}-1,3,3-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1359]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1360]      1 H NMR (CDCl 3 ), δ ppm: 1.02 (3H, br), 1.53 (3H, br), 3.40 (3H, s), 3.47 (3H, s), 3.84 (2H, s), 3.90 (2H, s), 4.67 (2H, s), 6.97 (1H, d, J=8.2 Hz), 7.18 (1H, dd, J=8.2, 1.7 Hz), 7.23-7.26 (2H, m), 7.72 (1H, dd, J=7.7, 1.6 Hz), 7.94 (1H, br), 8.50 (1H, dd, Jr-4.8, 1.6 Hz). 
       Example 765 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-3,3-dimethyl-7-{[(2-methyl pyridin-3-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1361]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1362]      1 H NMR (CDCl 3 ), δ ppm: 0.12-0.22 (2H, m), 0.34-0.50 (2H, m), 0.82 (3H, s), 0.94-1.03 (1H, m), 1.53 (3H, s), 2.56 (3H, s), 3.31 (3H, s), 3.49-3.60 (2H, m), 3.70 (1H, ddd, J=10.0, 7.1, 5.5 Hz), 3.81 (2H, s), 3.87 (2H, s), 3.94 (1H, dt, J=13.9, 5.3 Hz), 4.12 (1H, dd, J=14.1, 7.4 Hz), 4.15-4.22 (1H, m), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.24-7.26 (2H, m), 7.33 (1H, br), 7.50 (1H, d, J=8.4 Hz), 7.63 (1H, dd, J=7.6, 1.6 Hz), 8.41 (1H, dd, J=4.9, 1.6 Hz). 
       Example 766 
     5-Cyclopropylmethyl-1-(2-methoxyethyl)-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]-methyl}-3,3-dimethyl-1,5-dihydro-benzo[b][1,4 ]diazepine-2,4-dione 
       [1363]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1364]      1 H NMR (CDCl 3 ), δ ppm: 0.12-0.23 (2H, m), 0.34-0.44 (2H, m), 0.82 (3H, s), 0.96-1.03 (1H, m), 1.53 (3H, s), 3.30 (3H, s), 3.40 (3H, s), 3.49-3.60 (2H, m), 3.69 (1H, ddd, J=10.0, 7.1, 5.5 Hz), 3.84 (2H, s), 3.89 (2H, s), 3.95 (1H, dt, J=13.9, 5.3 Hz), 4.11-4.22 (2H, m), 4.66 (2H, s), 7.23-7.26 (2H, m), 7.32 (1H, br), 7.49 (1H, d, J=8.4 Hz), 7.72 (1H, dd, J=7.6, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 767 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-3,3-dimethyl-7-{[(2-methyl pyridin-3-ylmethyl)-amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1365]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1366]      1 H NMR (CDCl 3 ), δ ppm: 0.11-0.22 (2H, m), 0.34-0.44 (2H, m), 0.82 (3H, s), 0.94-1.03 (1H, m), 1.52 (3H, s), 2.56 (3H, s), 3.29 (3H, s), 3.49-3.57 (2H, m), 3.71 (1H, ddd, J=10.0, 7.1, 5.5 Hz), 3.82 (2H, s), 3.87 (2H, s), 3.97 (1H, dt, J=13.9, 5.2 Hz), 4.11-4.22 (2H, m), 7.12 (1H, dd, J=7.6, 4.9 Hz), 7.23-7.27 (2H, m), 7.55 (1H, d, J=1.3 Hz), 7.64 (1H, dd, J=7.6, 1.6 Hz), 8.40 (1H, dd, J=4.9, 1.6 Hz). 
       Example 768 
     1-Cyclopropylmethyl-5-(2-methoxyethyl)-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]-methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1367]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1368]      1 H NMR (CDCl 3 ), δ ppm: 0.11-0.22 (2H, m), 0.34-0.44 (2H, m), 0.82 (3H, s), 0.94-1.04 (1H, m), 1.52 (3H, s), 3.29 (3H, s), 3.40 (3H, s), 3.48-3.57 (2H, m), 3.70 (1H, ddd, J=10.0, 7.0, 5.6 Hz), 3.85 (2H, s), 3.90 (2H, s), 3.96 (1H, dt, J=13.9, 5.3 Hz), 4.14 (1H, dd, J=14.1, 7.4 Hz), 4.18-4.25 (1H, m), 4.67 (2H, s), 7.23-7.29 (3H, m), 7.52 (1H, br), 7.75 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 769 
     5-Cyclopropyl-1-cyclopropylmethyl-7-{[(2-methoxymethylpyridin-3-ylmethyl)amino]methyl}-3,3-dimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1369]    The synthesis of the title compound was performed in the same manner as in Example 721 using appropriate starting materials. 
         [1370]      1 H NMR (CDCl 3 ), δ ppm: 0.00-0.06 (1H, m), 0.07-0.13 (1H, m), 0.18-0.35 (3H, m), 0.58-0.65 (1H, m), 0.75-0.90 (2H, m), 0.84 (3H, s), 1.14-1.22 (1H, m), 1.51 (3H, s), 3.20-3.25 (1H, m), 3.36 (1H, dd, J=14.1, 6.8 Hz), 3.40 (3H, s), 3.86 (2H, s), 3.90 (2H, s), 4.30 (1H, dd, J=14.1, 7.4 Hz), 4.67 (2H, s), 7.18-7.26 (3H, m), 7.36 (1H, br), 7.73 (1H, dd, J=7.7, 1.6 Hz), 8.50 (1H, dd, J=4.8, 1.6 Hz). 
       Example 770 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1371]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 165.3-166.5° C. 
     Example 771 
     7-{2-[N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylpyridin-3-ylmethyl)amino]ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1372]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 155.1-155.8° C. 
     Example 772 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-2-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1373]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1374]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.23 (3H, d, J=0.9 Hz), 2.42 (3H, d, J=0.8 Hz), 2.76 (2H, t, J=7.4 Hz), 2.84-2.92 (2H, m), 2.95-3.04 (2H, m), 3.36 (3H, s), 3.71-3.79 (1H, m), 4.01 and 4.02 (2H, s), 4.03-4.16 (3H, m), 6.77 (1H, br), 6.93 (1H, br), 6.97-7.01 (m, 3H), 7.12 (1H, d, J=9.0 Hz), 7.52 (1H, d, J=2.1 Hz). 
       Example 773 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-2-ylmethyl)amino]ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1375]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1376]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.41 (3H, s), 2.42 (3H, s), 2.75 (2H, t, J=7.4 Hz), 2.83-2.91 (2H, m), 2.99 (2H, t, J=6.4 Hz), 3.36 (3H, s), 3.72-3.79 (1H, m), 4.01 (2H, s), 4.07 (2H, t, J=6.4 Hz), 4.09-4.16 (1H, m), 6.43 (1H, d, J=7.3 Hz), 6.55 (1H, s), 6.77 (1H, br), 6.98-7.02 (m, 2H), 7.06 (1H, d, J=7.3 Hz), 7.13 (1H, d, J=8.7 Hz). 
       Example 774 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-methylpyridin-2-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1377]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1378]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.24 (3H, s), 2.41 (3H, d, J=0.9 Hz), 2.79-2.85 (2H, m), 2.88-2.93 (2H, m), 2.95 (2H, t, J=6.8 Hz), 3.37 (3H, s), 3.71-3.79 (1H, m), 3.89 (2H, s), 3.94-3.98 (2H, m), 4.10-4.17 (1H, m), 6.34 (1H, d, J=7.4 Hz), 6.53 (1H, br), 6.89 (1H, d, J=7.4 Hz), 7.01 (1H, d, J=1.8 Hz), 7.04 (1H, dd, J=1.8, 8.3 Hz), 7.12 (1H, dd, J=4.8, 7.6 Hz), 7.16 (1H, d, J=8.30 Hz), 7.37 (1H, dd, LT=1.1, 7.6 Hz), 8.39 (1H, dd, J=1.1, 4.8 Hz). 
       Example 775 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-methylpyridin-2-ylmethyl)amino]ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1379]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1380]      1 H NMR (CDCl 3 ), δ ppm: 0.80 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.17 (3H, d, J=1.0 Hz), 2.22 (3H, s), 2.81-2.87 (2H, m), 2.89-2.97 (4H, m), 3.38 (3H, s), 3.71-3.80 (1H, m), 3.88 (2H, s), 3.93-4.00 (2H, m), 4.09-4.18 (1H, m), 6.70 (1H, br), 6.96 (1H, d, J=2.1 Hz), 7.03 (1H, d, J=1.8 Hz), 7.06 (1H, dd, J=1.8, 8.3 Hz), 7.11 (1H, dd, J=4.8, 7.6 Hz), 7.17 (1H, d, J=8.3 Hz), 7.34 (1H, dd, J=1.2, 7.6 Hz), 7.50 (1H, d, J=2.1 Hz), 8.39 (1H, dd, J=1.2, 4.8 Hz). 
       Example 776 
     7-{2-[N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(3-methylpyridin-2-ylmethyl)amino]ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1381]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1382]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.14 (3H, d, J=1.0 Hz), 2.23 (3H, s), 2.42 (3H, d, J=1.0 Hz), 2.80-2.86 (2H, m), 2.88-2.96 (4H, m), 3.38 (3H, s), 3.71-3.79 (1H, m), 3.88 (2H, s), 3.91-3.99 (2H, m), 4.10-4.16 (1H, m), 6.54 (1H, br), 6.63 (1H, br), 7.02 (1H, d, J=1.9 Hz), 7.05 (1H, dd, J=1.9, 8.3 Hz), 7.12 (1H, dd, J=4.8, 7.6 Hz), 7.16 (1H, d, J=8.3 Hz), 7.36 (1H, dd, J=1.1, 7.6 Hz), 8.39 (1H, dd, J=1.1, 4.8 Hz). 
       Example 777 
     N-[2-({N′-[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)ethyl]-N′-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)phenyl]methanesulfonamide 
       [1383]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1384]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.42 (3H, d, J=1.0 Hz), 2.78-2.98 (6H, m), 3.03 (3H, s), 3.36 (3H, s), 3.70-3.83 (1H, m), 3.88 (2H, s), 4.06-4.22 (3H, m), 6.43-6.45 (1H, m), 6.53 (1H, t, J=0.92 Hz), 6.97 (1H, d, J=1.8 Hz), 6.99-7.03 (1H, m), 7.04 (1H, d, J=7.4 Hz), 7.06-7.11 (1H, m), 7.14-7.18 (1H, m), 7.19 (1H, d, J=8.4 Hz), 7.30-7.35 (1H, m), 7.44 (1H, dd, J=0.96, 8.1 Hz), 9.88 (1H, bs). 
       Example 778 
     N-[2-({N′-[2-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)ethyl]-N′-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)phenyl]methanesulfonamide 
       [1385]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1386]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.0 Hz), 1.52 (3H, s), 2.24 (3H, s), 2.79-2.97 (6H, m), 3.01 (3H, s), 3.36 (3H, s), 3.71-3.83 (1H, m), 3.87 (2H, s), 4.06-4.20 (3H, m), 6.87 (1H, d, J=1.0 Hz), 6.94-6.99 (2H, m), 7.02 (1H, dd, J=1.9, 8.3 Hz), 7.05-7.13 (1H, m), 7.13-7.18 (1H, m), 7.19 (1H, d, J=8.3 Hz), 7.29-7.36 (1H, m), 7.43 (1H, d, J=8.0 Hz), 7.53 (1H, d, J=2.1 Hz), 9.84 (1H, bs). 
       Example 779 
     N-[2-({N′-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N′-[2-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yl)ethyl]amino}methyl)phenyl]methanesulfonamide 
       [1387]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1388]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.17 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.21 (3H, d, J=1.0 Hz), 2.43 (3H, d, J=1.0 Hz), 2.78-2.97 (6H, m), 3.02 (3H, s), 3.36 (3H, s), 3.72-3.85 (1H, m), 3.87 (2H, s), 4.04-4.19 (3H, m), 6.54 (1H, d, J=1.2 Hz), 6.81 (1H, d, J=1.1 Hz), 6.97 (1H, d, J=1.9 Hz), 7.01 (1H, dd, J=1.9, 8.3 Hz), 7.06-7.13 (1H, m), 7.13-7.17 (1H, m), 7.19 (1H, d, J=8.3 Hz), 7.29-7.36 (1H, m), 7.44 (1H, dd, J=0.92, 8.1 Hz), 9.75 (1H, bs). 
       Example 780 
     7-{2-[N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)amino]ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1389]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 168.5-170.5° C. 
     Example 781 
     7-(2-{N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1390]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 133.5-139.7° C. 
     Example 782 
     7-(2-{N-(2,5-Dimethyl-2H-pyrazol-3-ylmethyl)-N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}ethyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1391]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [0000]    White powder 
       mp: 171-172.9° C. 
     Example 783 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1392]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1393]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.39 (3H, s), 2.42 (3H, s), 2.70-2.85 (4H, m), 2.91 (2H, t, J=6.4 Hz), 3.36 (3H, s), 3.71-3.78 (1H, m), 3.83 (2H, s), 4.03 (2H, t, J=6.4 Hz), 4.06-4.16 (1H, m), 6.42 (1H, dd, J=0.8 and 7.4 Hz), 6.55 (1H, t, J=1.0 Hz), 6.95-7.02 (3H, m), 7.13 (1H, d, J=8.8 Hz), 8.58 (1H, s) 
       Example 784 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1394]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1395]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.24 (3H, s), 2.39 (3H, s), 2.70-2.85 (4H, m), 2.88-2.95 (2H, m), 3.36 (3H, s), 3.70-3.80 (1H, m), 3.82 (2H, s), 4.00-4.18 (3H, m), 6.86 (1H, d, J=1.0 Hz), 6.95-7.03 (3H, m), 7.12 (1H, d, J=8.2 Hz), 7.52 (1H, d, 2.1 Hz), 8.59 (1H, s) 
       Example 785 
     7-{2-[N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(4-methylthiazol-5-ylmethyl)amino]ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1396]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1397]      1 H NMR (CDCl 3 ), δ ppm: 0.79 (3H, s), 1.16 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.21 (3H, s), 2.39 (3H, s), 2.43 (3H, s), 2.70-2.85 (4H, m), 2.88-2.96 (2H, m), 3.36 (3H, s), 3.70-3.85 (3H, m), 3.96-4.18 (3H, m), 6.56 (1H, d, J=1.1 Hz), 6.79 (1H, d, J=1.1 Hz), 6.95-7.00 (2H, m), 7.12 (1H, d, J=8.6 Hz), 8.60 (1H, s) 
         [1398]    The following compounds shown in Examples 786 to 791, Examples 793 and Example 795 to 802 can be prepared by the same manner as mentioned above or a conventional manner using appropriate starting materials. 
       Example 786 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-(2-methylpyridin-3-ylmethyl)-N-(2-pyridin-3-ylethyl)amino]ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 787 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(7-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]ethyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 788 
     7-{2-[N-[2-(2,7-Dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyridin-3-ylmethyl)amino]ethyl}-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 789 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-methylpyrimidin-5-ylmethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 790 
     N-[3-({N′-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-benzo[b][1,4]diazepin-7-ylmethyl)-N′-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]amino}methyl)pyridin-2-yl]methanesulfonamide 
     Example 791 
     N-[3-({N′-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N′-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridin-2-yl]acetamide 
     Example 792 
     Acetic acid 3-({N-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)pyridin-2-ylmethyl ester dihydrochloride 
       [1399]    The synthesis of the title compound was performed in the same manner as in Example 4 using appropriate starting materials. 
         [1400]      1 H NMR (DMSO-d 6 ), δ ppm: 0.69 (3H, s), 1.04 (3H, t, J=6.9 Hz), 1.34 (3H, s), 2.01-2.04 (3H, m), 2.42 (3H, s), 2.74 (2H, br), 3.26 (3H, s), 3.45-4.30 (8H, m), 5.10 (2H, br), 6.48 (1H, br), 6.64 (1H, br), 7.17 (1H, br), 7.31 (2H, br), 7.48 (2H, br), 7.79 (1H, br), 8.46 (1H, br). 
       Example 793 
     1-Ethyl-7-({N-(2-imidazol-1-ylmethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 794 
     1-Ethyl-7-({N-(3-imidazol-1-ylmethylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1401]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1402]      1 H NMR (CDCl 3 ), δ ppm: 0.77 (3H, s), 1.17 (3H, t, J=7.0 Hz), 1.51 (3H, s), 2.43 (3H, d, J=1.0 Hz), 2.79 (2H, dt, J=2.1, 5.9 Hz), 3.32 (3H, s), 3.55-3.68 (4H, m), 3.71-3.83 (1H, m), 3.99-4.17 (3H, m), 5.02 (2H, s), 6.43 (1H, dd, J=0.74, 7.3 Hz), 6.49 (1H, t, J=1.0 Hz), 6.88 (1H, t, J=1.3 Hz), 6.95 (1H, d, J=7.3 Hz), 6.98-7.07 (3H, m), 7.07-7.15 (3H, m), 7.15-7.25 (2H, m), 7.52 (1H, d, J=1.1 Hz). 
       Example 795 
     1-Ethyl-7-({N-(2-imidazol-1-ylbenzyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 796 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-morpholin-4-ylbenzyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 797 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-[1,2,4]triazol-1-yl-benzyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 798 
     1-Ethyl-7-(N-{imidazo[1,2-a]pyridin-8-ylmethyl-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 799 
     1-Ethyl-7-(N-{imidazo[1,2-a]pyridin-6-ylmethyl-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 800 
     1-Ethyl-3,3,5-trimethyl-7-{[N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]-N-(2-pyrazol-1-ylpyridin-3-ylmethyl)amino]methyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 801 
     7-({N-(3H-Benzoimidazol-4-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
     Example 802 
     1-Ethyl-7-({N-(4-methoxymethylpyridin-3-ylmethyl)-N-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)ethyl]amino}methyl)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
     Example 802-a 
     1-Ethyl-3,3,5-trimethyl-7-{2-[N-[2-(2,7-dimethyl-4-oxo-4H-furo[3,2-c]pyridin-5-yl)-ethyl]-N-(4-methyl-thiazol-2-ylmethyl)-amino]-ethyl}-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione 
       [1403]    The synthesis of the title compound was performed in the same manner as in Example 30 using appropriate starting materials. 
         [1404]      1 H NMR (CDCl 3 ), δ ppm: 0.78 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.51 (3H, s), 2.20 (3H, d, J=0.9 Hz), 2.42 (3H, d, J=0.9 Hz), 2.43 (3H, d, J=0.9 Hz), 2.76 (2H, t, J=7.4 Hz), 2.85-2.90 (2H, m), 2.95-3.02 (2H, m), 3.35 (3H, s), 3.71-3.77 (1H, m), 4.01 and 4.02 (2H, s), 4.02-4.16 (3H, m), 6.57 (1H, br), 6.77 (1H, br), 6.86 (1H, br), 6.97-7.01 (m, 2H), 7.12 (1H, d, J=8.9 Hz). 
       Examples 803 to 1038 
       [1405]    The following compounds were obtained in the same manner as in Examples above using appropriate starting materials. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 803 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 804 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 500 
               
               
                   
               
               
                 805 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 500 
               
               
                   
               
               
                 806 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 503 
               
               
                   
               
               
                 807 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
               
               
                 808 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 519 
               
               
                   
               
               
                 809 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 506 
               
               
                   
               
               
                 810 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 811 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 515 
               
               
                   
               
               
                 812 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 813 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 568 
               
               
                   
               
               
                 814 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 815 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 520 
               
               
                   
               
               
                 816 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 817 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 534 
               
               
                   
               
               
                 818 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 520 
               
               
                   
               
               
                 819 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 533 
               
               
                   
               
               
                 820 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 520 
               
               
                   
               
               
                 821 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 822 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 823 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 824 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 825 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 826 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 503 
               
               
                   
               
               
                 827 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 828 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 503 
               
               
                   
               
               
                 829 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 830 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 518 
               
               
                   
               
               
                 831 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 568 
               
               
                   
               
               
                 832 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 530 
               
               
                   
               
               
                 833 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 506 
               
               
                   
               
               
                 834 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 506 
               
               
                   
               
               
                 835 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 836 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
               
               
                 837 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 838 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 839 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 530 
               
               
                   
               
               
                 840 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 504 
               
               
                   
               
               
                 841 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 842 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
               
               
                 843 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
               
               
                 844 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 504 
               
               
                   
               
               
                 845 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 588 
               
               
                   
               
               
                 846 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 515 
               
               
                   
               
               
                 847 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 528 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 848 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 849 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 850 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 851 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 852 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 561 
               
               
                   
               
               
                 853 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 575 
               
               
                   
               
               
                 854 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 855 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 856 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 857 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 858 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 624 
               
               
                   
               
               
                 859 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 860 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 861 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 613 
               
               
                   
               
               
                 862 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 
               
               
                   
               
               
                 863 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 864 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 589 
               
               
                   
               
               
                 865 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 866 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 867 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 868 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 869 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 870 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 871 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 872 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 873 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 
               
               
                   
               
               
                 874 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 875 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 876 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 877 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 878 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 624 
               
               
                   
               
               
                 879 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 880 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 881 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 882 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 883 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 884 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 885 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 886 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 887 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 
               
               
                   
               
               
                 888 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 889 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 890 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 891 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 
               
               
                   
               
               
                 892 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 644 
               
               
                   
               
               
                 893 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 894 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 895 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 896 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 566 
               
               
                   
               
               
                 897 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 566 
               
               
                   
               
               
                 898 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 569 
               
               
                   
               
               
                 899 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 900 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 585 
               
               
                   
               
               
                 901 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
               
               
                 902 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 583 
               
               
                   
               
               
                 903 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 581 
               
               
                   
               
               
                 904 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 555 
               
               
                   
               
               
                 905 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 634 
               
               
                   
               
               
                 906 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 583 
               
               
                   
               
               
                 907 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 908 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 623 
               
               
                   
               
               
                 909 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 600 
               
               
                   
               
               
                 910 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 911 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 599 
               
               
                   
               
               
                 912 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 913 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 914 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 915 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 916 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 917 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 918 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 
               
               
                   
               
               
                 919 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 569 
               
               
                   
               
               
                 920 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 600 
               
               
                   
               
               
                 921 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 583 
               
               
                   
               
               
                 922 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 569 
               
               
                   
               
               
                 923 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 924 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 
               
               
                   
               
               
                 925 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 634 
               
               
                   
               
               
                 926 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 927 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
               
               
                 928 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 572 
               
               
                   
               
               
                 929 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 
               
               
                   
               
               
                 930 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 931 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 567 
               
               
                   
               
               
                 932 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 933 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 596 
               
               
                   
               
               
                 934 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 935 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 580 
               
               
                   
               
               
                 936 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 937 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 938 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 939 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 654 
               
               
                   
               
               
                 940 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 581 
               
               
                   
               
               
                 941 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 594 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 942 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 943 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 944 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 556 
               
               
                   
               
               
                 945 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 946 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 561 
               
               
                   
               
               
                 947 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 575 
               
               
                   
               
               
                 948 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 949 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 950 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 951 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 545 
               
               
                   
               
               
                 952 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 624 
               
               
                   
               
               
                 953 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 954 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 955 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 613 
               
               
                   
               
               
                 956 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 
               
               
                   
               
               
                 957 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 958 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 589 
               
               
                   
               
               
                 959 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 576 
               
               
                   
               
               
                 960 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 961 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 962 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 963 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 964 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 965 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 966 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 967 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 590 
               
               
                   
               
               
                 968 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 573 
               
               
                   
               
               
                 969 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 559 
               
               
                   
               
               
                 970 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 971 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 574 
               
               
                   
               
               
                 972 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 624 
               
               
                   
               
               
                 973 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 974 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 975 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 562 
               
               
                   
               
               
                 976 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 977 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 978 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 557 
               
               
                   
               
               
                 979 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 980 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 586 
               
               
                   
               
               
                 981 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 
               
               
                   
               
               
                 982 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 570 
               
               
                   
               
               
                 983 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 984 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 546 
               
               
                   
               
               
                 985 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 560 
               
               
                   
               
               
                 986 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 644 
               
               
                   
               
               
                 987 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 571 
               
               
                   
               
               
                 988 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 584 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
             
          
           
               
                 989 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 406 
               
               
                   
               
               
                 990 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 421 
               
               
                   
               
               
                 991 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 992 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 993 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 452 
               
               
                   
               
               
                 994 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 436 
               
               
                   
               
               
                 995 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 440 
               
               
                   
               
               
                 996 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 392 
               
               
                   
               
               
                 997 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 998 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 438 
               
               
                   
               
               
                 999 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 1000 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 1001 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 421 
               
               
                   
               
               
                 1002 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 421 
               
               
                   
               
               
                 1003 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 438 
               
               
                   
               
               
                 1004 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 1005 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 406 
               
               
                   
               
               
                 1006 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 407 
               
               
                   
               
               
                 1007 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 420 
               
               
                   
               
               
                 1008 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 421 
               
               
                   
               
               
                 1009 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 419 
               
               
                   
               
               
                 1010 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 420 
               
               
                   
               
               
                 1011 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 450 
               
               
                   
               
               
                 1012 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 454 
               
               
                   
               
               
                 1013 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 426 
               
               
                   
               
               
                 1014 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 452 
               
               
                   
               
               
                 1015 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 407 
               
               
                   
               
               
                 1016 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 452 
               
               
                   
               
               
                 1017 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1018 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 450 
               
               
                   
               
               
                 1019 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 436 
               
               
                   
               
               
                 1020 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1021 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 436 
               
               
                   
               
               
                 1022 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 452 
               
               
                   
               
               
                 1023 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1024 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1025 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 408 
               
               
                   
               
               
                 1026 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 1027 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 411 
               
               
                   
               
               
                 1028 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1029 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 422 
               
               
                   
               
               
                 1030 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 1031 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 421 
               
               
                   
               
               
                 1032 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 496 
               
               
                   
               
               
                 1033 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 1034 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 1035 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 1036 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 449 
               
               
                   
               
               
                 1037 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 1038 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
             
          
         
       
     
       Examples 1039 to 1614 
       [1406]    The following compounds can be obtained in the same manner as in Examples above using appropriate starting materials. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1039 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1040 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1041 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1042 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1043 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1044 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1045 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1046 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1047 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1048 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1049 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1050 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1051 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1052 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1053 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1054 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1055 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1056 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1057 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1058 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1059 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1060 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1061 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1062 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1063 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1064 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1065 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1066 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1067 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1068 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1069 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1070 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1071 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1072 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1073 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1074 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1075 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1076 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1077 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1078 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1079 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1080 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1081 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1082 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1083 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1084 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1085 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1086 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1087 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1088 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1089 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1090 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1091 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1092 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1093 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1094 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1095 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1096 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1097 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1098 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1099 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1100 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1101 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1102 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1103 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1104 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1105 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1106 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1107 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1108 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1109 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1110 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1111 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1112 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1113 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1114 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1115 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1116 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1117 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1118 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1119 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1120 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1121 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1122 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1123 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1124 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1125 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1126 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1127 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1128 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1129 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1130 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1131 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1132 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1133 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1134 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1135 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1136 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1137 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1138 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1139 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1140 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1141 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1142 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1143 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1144 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1145 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1146 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1147 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1148 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1149 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1150 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1151 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1152 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1153 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1154 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1155 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1156 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1157 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1158 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1159 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1160 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1161 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1162 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1163 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1164 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1165 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1166 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1167 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1168 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1169 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1170 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1171 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1172 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1173 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1174 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1175 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1176 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1177 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1178 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1179 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1180 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1181 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1182 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1183 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1184 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1185 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1186 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1187 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1188 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1189 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1190 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1191 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1192 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1193 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1194 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1195 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1196 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1197 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1198 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1199 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1200 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1201 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1202 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1203 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1204 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1205 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1206 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1207 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1208 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1209 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1210 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1211 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1212 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1213 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1214 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1215 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1216 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1217 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1218 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1219 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1220 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1221 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1222 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1223 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1224 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1225 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1226 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1227 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1228 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1229 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1230 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1231 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1232 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1233 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1234 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1235 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1236 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1237 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1238 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1239 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1240 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1241 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1242 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1243 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1244 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1245 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1246 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1247 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1248 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1249 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1250 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1251 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1252 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1253 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1254 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1255 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1256 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1257 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1258 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1259 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1260 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1261 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1262 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1263 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1264 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1265 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1266 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1267 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1268 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1269 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1270 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1271 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1272 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1273 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1274 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1275 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1276 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1277 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1278 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1279 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1280 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1281 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1282 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1283 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1284 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1285 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1286 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1287 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1288 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1289 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1290 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1291 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1292 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1293 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1294 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1295 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1296 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1297 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1298 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1299 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1300 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1301 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1302 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1303 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1304 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1305 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1306 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1307 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1308 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1309 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1310 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1311 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1312 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1313 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1314 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1315 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1316 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1317 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1318 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1319 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1320 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1321 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1322 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1323 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1324 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1325 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1326 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1327 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1328 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1329 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1330 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1331 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1332 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1333 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1334 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1335 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1336 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1337 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1338 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1339 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1340 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1341 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1342 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1343 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1344 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1345 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1346 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1347 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1348 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1349 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1350 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1351 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1352 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1353 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1354 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1355 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1356 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1357 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1358 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1359 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1360 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1361 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1362 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1363 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1364 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1365 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1366 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1367 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1368 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1369 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1370 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1371 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1372 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1373 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1374 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS (M + 1) 
               
               
                   
               
               
                 1375 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1376 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1377 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1378 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1379 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1380 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1381 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1382 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1383 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1384 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1385 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1386 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1387 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1388 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1389 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1390 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1391 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1392 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1393 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1394 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1395 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1396 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1397 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1398 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1399 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1400 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1401 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1402 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1403 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1404 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1405 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1406 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1407 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1408 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1409 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1410 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1411 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1412 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1413 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1414 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1415 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1416 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1417 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1418 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1419 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1420 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1421 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1422 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example  
                   
                 MS  
               
               
                 No. 
                 R1 
                 (M + 1) 
               
               
                   
               
               
                 1423 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1424 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1425 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1426 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1427 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1428 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1429 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1430 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1431 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1432 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1433 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1434 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1435 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1436 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1437 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1438 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1439 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1440 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1441 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1442 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1443 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1444 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1445 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1446 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1447 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1448 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1449 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1450 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1451 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1452 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1453 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1454 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1455 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1456 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1457 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1458 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1459 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1460 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1461 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1462 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1463 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1464 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1465 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1466 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1467 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1468 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1469 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1470  
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example  
                   
                 MS  
               
               
                 No. 
                 R1 
                 (M + 1) 
               
               
                   
               
               
                 1471 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1472 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1473 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1474 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1475 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1476 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1477 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1478 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1479 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1480 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1481 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1482 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1483 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1484 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1485 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1486 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1487 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1488 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1489 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1490 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1491 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1492 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1493 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1494 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1495 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1496 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1497 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1498 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1499 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1500 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1501 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1502 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1503 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1504 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1505 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1506 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1507 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1508 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1509 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1510 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1511 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1512 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1513 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1514 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1515 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1516 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1517 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1518  
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example  
                   
                 MS  
               
               
                 No. 
                 R1 
                 (M + 1) 
               
               
                   
               
               
                 1519 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1520 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1521 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1522 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1523 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1524 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1525 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1526 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1527 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1528 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1529 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1530 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1531 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1532 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1533 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1534 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1535 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1536 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1537 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1538 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1539 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1540 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1541 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1542 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1543 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1544 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1545 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1546 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1547 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1548 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1549 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1550 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1551 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1552 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1553 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1554 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1555 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1556 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1557 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1558 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1559 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1560 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1561 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1562 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1563 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1564 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1565 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1566  
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example  
                   
                 MS  
               
               
                 No. 
                 R1 
                 (M + 1) 
               
               
                   
               
               
                 1567 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1568 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1569 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1570 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1571 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1572 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1573 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1574 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1575 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1576 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1577 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1578 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1579 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1580 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1581 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1582 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1583 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1584 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1585 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1586 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1587 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1588 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1589 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1590 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1591 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1592 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1593 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1594 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1595 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1596 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1597 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1598 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1599 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1600 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1601 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1602 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1603 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1604 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1605 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1606 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1607 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1608 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1609 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1610 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1611 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1612 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1613 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
               
               
                   
               
               
                 1614  
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
         
       
     
       Examples 1615 to 1625 
       [1407]    The following compounds were obtained in the same manner as in Examples above using appropriate starting materials. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 1615 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 450 
               
               
                   
               
               
                 1616 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 450 
               
               
                   
               
               
                 1617 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 465 
               
               
                   
               
               
                 1618 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 438 
               
               
                   
               
               
                 1619 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 432 
               
               
                   
               
               
                 1620 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 445 
               
               
                   
               
               
                 1621 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 432 
               
               
                   
               
               
                 1622 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 460 
               
               
                   
               
               
                 1623 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 463 
               
               
                   
               
               
                 1624 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 459 
               
               
                   
               
               
                 1625 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 432 
               
               
                   
               
             
          
         
       
     
       Pharmacological Test 1 
     (1) Production of Human Kv1.5-Expressing CHO-K1 Cell Lines 
       [1408]    CHO-K1 cell lines stably expressing human Kv1.5 channels were prepared in the following manner. 
         [1409]    Full-length human Kv1.5 cDNA was cloned from a human heart cDNA library (produced by Stratagene). The obtained human Kv1.5 sequence corresponds to the sequence described in FASEB J. 5, 331-337 (1991). 
         [1410]    The obtained human Kv1.5 cDNA was inserted into a plasmid encoding a CMV promoter and a G418 resistance marker to produce a Kv1.5 expression vector. The human Kv1.5 expression vector was transfected into CHO-K1 cells by the lipofectamine method. After culturing the cells in an F-12 medium (produced by Invitrogen Corp.) containing 10% FBS (produced by Invitrogen Corp.) for 3 or 4 days, the medium was replaced with a FBS-containing F-12 medium that included 1,000 μg/ml of G418 (produced by Invitrogen Corp.), and single colonies were isolated. The amount of Kv1.5 channel expression in the single colonies was quantified at the mRNA level by RT-PCR and then quantified at the protein level by western blotting. Finally, the expressed current was analyzed by patch clamp method. Cell lines expressing a current of 200 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamp method. 
       (2) Production of CHO Cell Line Expressing Human GIRK1/4 
       [1411]    CHO cell lines stably expressing human GIRK1/4 channels were prepared in the following manner. 
         [1412]    Full-length human GIRK1 cDNA was cloned from HuH cell- and HeLa cell-derived cDNA libraries. Full-length GIRK4 cDNA was amplified from a human heart cDNA library (produced by Clontech Laboratories, Inc.) by PCR using synthetic primers shown in Table 1, and cloned into the Eco-RI restriction enzyme site of pCR-Blunt (produced by Invitrogen Corporation) or into the HincII site of pUC118 (produced by Takara Bio, Inc.). 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Primer 
                 Sequence 
                   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 hGIRK1-S 
                 5′-ATGTCTGCACTCCGAAGGAAATTTG-3′ 
                 SEQ ID No. 1 
               
               
                   
               
               
                 hGIRK1-A 
                 5′-TTATGTGAAGCGATCAGAGTTC-3′ 
                 SEQ ID No. 2 
               
               
                   
               
               
                 hGIRK1-F2 
                 5′-GCAGGGTACCCCTTCGTATTATGTCTGCACTCC-3′ 
                 SEQ ID No. 3 
               
               
                   
               
               
                 hGIRK1-A3 
                 5′-GGTGTCTGCCGAGATTTGA-3′ 
                 SEQ ID No. 4 
               
               
                   
               
               
                 hGIRK1-A4 
                 5′-CCGAGTGTAGGCGATCACCC-3′ 
                 SEQ ID No. 5 
               
               
                   
               
               
                 hGIRK4-S 
                 5′-ATGGCTGGCGATTCTAGGAATGCC-3′ 
                 SEQ ID No. 6 
               
               
                   
               
               
                 hGIRK4-A 
                 5′-TCTCACCGAGCCCCTGGCCTCCC-3′ 
                 SEQ ID No. 7 
               
               
                   
               
               
                 hGIRK4-S2 
                 5′-AACCAGGACATGGAGATTGG-3′ 
                 SEQ ID No. 8 
               
               
                   
               
               
                 hGIRK4-A2 
                 5′-GAGAACAGGAAAGCGGACAC-3′ 
                 SEQ ID No. 9 
               
               
                   
               
             
          
         
       
     
         [1413]    The obtained human GIRK1 and GIRK4 cDNA sequences correspond to known sequences (NCBI database: GIRK1 (NM — 002239) and GIRK4 (NM — 000890) respectively). The obtained GIRK1 and GIRK4 cDNA sequences were cloned into the Eco-RI restriction enzyme site of pCR-Blunt (available from Invitrogen Corporation) or into the HincII site of pUC118 (available from Takara Bio, Inc.). A GIRK4 expression vector was constructed by insertion into the BamHI-XhoI site of pcDNA5/FRT. A GIRK1 expression vector was constructed by insertion into the KpnI-XhoI site of pcDNA3.1(+) or pCAG_neo. FLP-IN-CHO cells (produced by Invitrogen Corporation) were transfected with human GIRK1 and GIRK4 expression vectors by using Lipofectamine 2000 (produced by Invitrogen Corporation) according to the protocol enclosed with the reagent or using an electronic induction method (“Nucleofector Kit-T”, produced by Amaxa). First, the cells transfected with the GIRK4 expression vector were cultured in a 10% serum-containing F12 medium (produced by Sigma) supplemented with 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. Then the cells expressing GIRK4 were transfected with the GIRK1 expression vector and were cultured in 10% serum-containing F12 medium supplemented with 350 μg/ml of G418 and 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. to select GIRK1/4 expressing cell lines. Cell populations whose growth was observed after about 2 weeks were isolated using cloning rings, and the obtained single colonies were proliferated. RNA was extracted from single colonies, and single-stranded cDNA was synthesized by a cDNA synthesis kit (produced by Invitrogen Corporation), and the amount of expression was quantified at the mRNA level by real-time PCR (Applied Biosystems, Ltd.). Finally, the expressed current was analyzed by patch clamp method described below. The cell lines expressing a current of 500 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamping method. 
       (3) Measurement of Ion Channel Current by Patch Clamp Method (Human Kv1.5-Expressing CHO-K1 Cell Line) 
       [1414]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolated table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human Kv1.5-expressing cells were cultured was placed in the perfusion chamber. 
         [1415]    Depolarizing stimulation pulses were applied and ionic current was recorded by using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, produced by HEKA) and a personal computer (manufactured by IBM Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, produced by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1416]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   40 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose 
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1417]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1418]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate 
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (4) Measurement of Ion Channel Current by Patch Clamp Method (Human GIRK1/4-Expressing CHO-K1 Cell Line) 
       [1419]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolation table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human GIRK1/4-expressing cells were cultured was placed in the perfusion chamber. 
         [1420]    Hyperpolarizing stimulation pulses were applied and ionic current was recorded using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, manufactured by HEKA) and a personal computer (manufactured by IBM Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, manufactured by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1421]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   4 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose  
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1422]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1423]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate  
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (5) Measurement of Human Kv1.5 Current 
       [1424]    While the membrane potential was holded at −80 mV, depolarizing pulses (−80 mV for 0.05 seconds→□□+40 mV for 0.2 seconds→□□−40 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure Kv1.5 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and holding the membrane potential at −80 mV, depolarizing pulses were applied. The current obtained during the pulse application was recorded as a current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and holding the membrane potential at −80 mV, depolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration was recorded. 
         [1425]    The data was analyzed by using the step end current recorded during the +40 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the +40 mV depolarizing pulse stimulation. 
         [1426]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (6) Measurement of Human GIRK1/4 Current 
       [1427]    While the membrane potential was holded at −80 mV, hyperpolarizing pulses (−80 mV for 0.05 seconds→□□−120 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure GIRK1/4 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. The current obtained during the pulse application was recorded as the current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration were recorded. 
         [1428]    The data was analyzed by using the step end current recorded during the −120 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the −120 mV depolarizing pulse stimulation. 
         [1429]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (7) Calculation of Inhibitory Activity on Ky1.5 Channel Ionic Current and GIRK1/4 Channel Current 
       [1430]    The concentration for 50% inhibition of Kv1.5 channel current or GIRK1/4 channel current (IC 50  value) was calculated according to the following nonlinear regression equation: 
         [0000]      Relative current=1/(1+[Concentration of the compound]/IC 50 ) nH    
         [0000]    wherein nH is the Hill coefficient. 
         [1431]    Table 2 shows the test results. 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Test Compound 
                 KV1.5 IC 50  (μM) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Compound of Example 10 
                 0.62 
               
               
                   
                 Compound of Example 15 
                 0.81 
               
               
                   
                 Compound of Example 16 
                 0.51 
               
               
                   
                 Compound of Example 18 
                 0.60 
               
               
                   
                 Compound of Example 35 
                 0.94 
               
               
                   
                 Compound of Example 41 
                 6.30 
               
               
                   
                 Compound of Example 42 
                 1.70 
               
               
                   
                 Compound of Example 43 
                 0.32 
               
               
                   
                 Compound of Example 48 
                 0.30 
               
               
                   
                 Compound of Example 104 
                 1.4 
               
               
                   
                 Compound of Example 317 
                 0.63 
               
               
                   
                 Compound of Example 318 
                 2.9 
               
               
                   
                 Compound of Example 330 
                 0.86 
               
               
                   
                   
               
             
          
         
       
     
       2. Second Invention 
     Reference Example 1 
     Synthesis of 6-hydroxy-2H-isoquinolin-1-one 
       [1432]    A 1.0M boron tribromide/dichloromethane solution (8.5 ml) was added at 0° C. to a dichloromethane solution (50 ml) of 6-methoxy-2H-isoquinolin-1-one (1.0 g). The mixture was stirred at room temperature overnight. Water and methanol were added to the reaction mixture and extraction was carried out with a dichloromethane/methanol mixed solvent (dichloromethane:methanol=10:1). The organic layer was dried with anhydrous sodium sulfate, followed by condensation to dryness under reduced pressure, thereby obtaining the title compound (0.4 g) as a pale yellow solid. 
         [1433]      1 H NMR (DMSO-d 6 ), δ ppm: 6.37 (1H, d, J=7.1 Hz), 6.86-6.94 (2H, m), 7.03-7.08 (1H, m), 8.02 (1H, d, J=8.7 Hz), 10.22 (1H, br), 10.90 (1H, s). 
       Reference Example 2 
     Synthesis of 6-hydroxy-1,3-dimethyl-3,4-dihydro-1H-quinazolin-2-one 
       [1434]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (DMSO-d 6 ), δ ppm: 2.87 (3H, s), 3.13 (3H, s), 4.26 (2H, s), 6.57 (1H, d, J=2.7 Hz), 6.65 (1H, dd, J=2.7, 8.7 Hz), 6.73 (1H, d, J=8.7 Hz), 9.13 (1H, s). 
       Reference Example 3 
     Synthesis of 6-hydroxy-1,3-dimethyl-1H-quinazoline-2,4-dione 
       [1435]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (DMSO-d 6 ) δ ppm: 3.29 (3H, s), 3.48 (3H, s), 7.20 (1H, dd, J=2.8, 9.0 Hz), 7.31 (1H, d, J=9.0 Hz), 7.40 (1H, d, J=2.8 Hz), 9.76 (1H, s). 
       Reference Example 4 
     Synthesis of 6-hydroxy-2-methyl-2H-isoquinolin-1-one 
       [1436]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (DMSO-d 6 ), δ ppm: 3.44 (3H, s), 6.43 (1H, d, J=7.4 Hz), 6.86 (1H, d, J=2.2 Hz), 6.93 (1H, dd, J=8.7, 2.2 Hz), 7.35 (1H, d, J=7.4 Hz), 8.04 (1H, d, J=8.7 Hz). 
       Reference Example 5 
     Synthesis of 6-hydroxy-2-methyl-3,4-dihydro-2H-isoquinolin-1-one 
       [1437]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (CDCl 3 ), δ ppm: 2.95 (2H, t, J=6.7 Hz), 3.13 (3H, s), 3.57 (2H, t, J=6.7 Hz), 6.62 (1H, d, J=2.4 Hz), 6.76 (1H, dd, J=8.6, 2.4 Hz), 7.83 (1H, d, J=8.6 Hz). 
       Reference Example 6 
     Synthesis of 2-methyl-1,1-dioxo-2,3-dihydro-1H-benzo[d]isothiazol-5-ol 
       [1438]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (CDCl 3 ), δ ppm: 2.92 (3H, s), 4.24 (2H, s), 6.75 (1H, s), 6.92 (1H, d, J=8.5 Hz), 7.60 (1H, d, J=8.5 Hz). 
       Reference Example 7 
     Synthesis of 3-hydroxy-7,8-dihydro-6H-5-thia-8-azabenzocyclohepten-9-one 
       [1439]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (CD 3 OD), δ ppm: 3.15 (2H, t, J=6.0 Hz), 3.21-3.40 (2H, m), 6.84 (1H, dd, J=8.4, 2.4 Hz), 6.96 (1H, d, J=2.4 Hz), 7.46 (1H, d, J=8.4 Hz). 
       Reference Example 8 
     Synthesis of 3-hydroxy-1-methyl-1H-quinolin-2-one 
       [1440]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials.  1 H-NMR (DMSO-d 6 , δ ppm: 3.70 (3H, s), 7.12 (1H, s), 7.17-7.28 (1H, m), 7.35-7.50 (2H, m), 7.56 (1H, d-d, J=1.3, 7.5 Hz), 9.46 (1H, br-s). 
       Reference Example 9 
     Synthesis of 7-(3-iodopropoxy)-1-methyl-1H-quinolin-2-one 
       [1441]    7-(3-Chloropropoxy)-1-methyl-1H-quinolin-2-one (2.5 g) and sodium iodide (3.0 g) were added to 30 ml of acetonitrile. The mixture was stirred for 18 hours while heated under reflux. After cooled to room temperature, water was added to the reaction mixture, followed by extraction using dichloromethane. The organic layer was dried with sodium sulfate and was condensed under reduced pressure to give the title compound (2.4 g) as a pale brown powder. 
         [1442]      1 H-NMR (CDCl 3 ), δ ppm: 2.29-2.37 (2H, m), 3.41 (2H, t, J=6.6 Hz), 3.69 (3H, s), 4.17 (2H, t, J=5.8 Hz), 6.56 (1H, d, J=9.4 Hz), 6.81-6.84 (2H, m), 7.45-7.58 (1H, m), 7.60 (1H, d, J=9.4 Hz). 
       Reference Example 10 
     Synthesis of 6-(5-bromopentyloxy)-1-methyl-1H-quinolin-2-one 
       [1443]    Sodium hydride (60% in oil, 440 mg) was suspended in DMF (20 ml), and was cooled to 0° C. in ice water bath. 6-(5-Bromopentyloxy)-1H-quinolin-2-one (3.1 g) was added thereto at the same temperature, and the mixture was stirred at 0° C. for an hour. Methyl iodide (1.9 ml) was added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1). The purified product was condensed to dryness under reduced pressure to give the title compound (2.68 g) as a yellow powder. 
         [1444]      1 H-NMR (CDCl 3 ), δ ppm: 1.53-1.70 (2H, m), 1.81-1.97 (4H, m), 3.45 (2H, t, J=6.7 Hz), 3.71 (3H, s), 4.00-4.04 (2H, m), 6.71 (1H, d, J=9.5 Hz), 7.00 (1H, d, J=3.0 Hz), 7.16-7.20 (1H, m), 7.27-7.31 (1H, m), 7.59 (1H, d, J=9.5 Hz). 
       Reference Example 11 
     Synthesis of 6-(8-bromooctyloxy)-2-methoxyquinoline 
       [1445]    Sodium hydride (60% in oil, 40 mg) was suspended in DMF (2 ml), and was cooled to 0° C. in ice water bath. 6-Hydroxy-2-methoxyquinoline (171 mg) was added thereto at the same temperature, and the mixture was stirred at 0° C. for an hour. 1,8-Dibromooctane (0.37 ml) was added thereto, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1). The purified product was condensed to dryness under reduced pressure to give the title compound (225 mg) as a white powder. 
         [1446]      1 H-NMR (CDCl 3 ), δ ppm: 1.37-1.51 (8H, m), 1.81-1.89 (4H, m), 3.41 (2H, t, J=6.8 Hz), 4.04 (3H, s), 4.04 (2H, t, J=6.5 Hz), 6.87 (1H, d, J=8.8 Hz), 7.03 (1H, d, J=2.8 Hz), 7.27 (1H, dd, J=9.1, 2.8 Hz), 7.75 (1H, d, J=9.1 Hz), 7.87 (1H, d J=8.8 Hz). 
       Reference Example 12 
     Synthesis of 6-(5-bromopentyloxy)-2-methoxyquinoline 
       [1447]    The synthesis of the title compound was performed in the same manner as in Reference Example 11 using appropriate starting materials. 
         [1448]      1 H-NMR (CDCl 3 ), δ ppm: 1.61-1.66 (2H, m), 1.821-1.96 (4H, m), 3.45 (2H, t, J=6.7 Hz), 3.47 (3H, s), 4.00-4.04 (2H, m), 6.70 (1H, d, J=9.5 Hz), 6.99 (1H, d, J=2.8 Hz), 7.17 (1H, dd, J=9.2, 2.8 Hz), 7.29 (1H, d J=9.2 Hz), 7.59 (1H, d, J=9.5 Hz). 
       Reference Example 13 
     Synthesis of 5-(3-iodopropoxy)-1-methyl-1H-quinolin-2-one 
       [1449]    The synthesis of the title compound was performed in the same manner as in Reference Example 9 using appropriate starting materials.  1 H-NMR (CDCl 3 ), δ ppm: 2.30-2.44 (2H, m), 3.42 (2H, t, J=6.7 Hz), 3.71 (3H, s), 4.19 (2H, t, J=5.8 Hz), 6.66 (1H, d, J=9.7 Hz), 6.70 (1H, d, J=8.1 Hz), 6.97 (1H, d, J=8.6 Hz), 7.48 (1H, dd, J=8.6, 8.1 Hz), 8.11 (1H, d, J=9.7 Hz). 
       Reference Example 14 
     Synthesis of 8-(3-iodopropoxy)-1-methyl-1H-quinolin-2-one 
       [1450]    The synthesis of the title compound was performed in the same manner as in Reference Example 9 using appropriate starting materials.  1 H-NMR (CDCl 3 ), δ ppm: 2.32-2.40 (2H, m), 3.39 (2H, t, J=6.6 Hz), 3.96 (3H, s), 4.15 (2H, t, J=5.9 Hz), 6.70 (1H, d, J=9.4 Hz), 7.08-7.17 (3H, m), 7.60 (1H, d, J=9.4 Hz). 
       Reference Example 15 
     Synthesis of (2-pyridin-3-yl-ethyl)-pyridin-4-ylmethyl-amine 
       [1451]    4-Pyridine carbaldehyde (5.36 g) and 3-(2-aminoethyl)pyridine (6.5 ml) were added to 100 ml of methanol. The mixture was stirred at room temperature for 7 hours. The mixture was cooled to 0° C., and sodium borohydride (2.8 g) was added thereto. The mixture was further stirred at 0° C. for an hour. Water was added to the reaction mixture and methanol was distilled off under reduced pressure. The residue was subjected to extraction using dichloromethane. The organic layer was washed with saturated saline, dried with anhydrous sodium sulfate, and was condensed under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:methanol=95:5→85:5). The purified product was condensed under reduced pressure to give the title compound (10.03 g) as a colorless oily matter. 
         [1452]      1 H-NMR (CDCl 3 ), δ ppm: 2.79-2.98 (4H, m), 3.82 (2H, s), 7.21 (2H, d, J=5.8 Hz), 7.20-7.27 (1H, m), 7.50-7.56 (1H, m), 8.48 (1H, dd, J=6.7, 1.6 Hz), 8.49 (1H, s), 8.51-8.57 (2H, m). 
       Reference Example 16 
     Synthesis of (2-pyridin-3-yl-ethyl)-pyridin-4-ylmethyl-[3-(tetrahydro-pyran-2-yloxy)-propyl]-amine 
       [1453]    Sodium iodide (1.5 g) was added to a DMF solution (20 ml) of 2-(3-bromopropoxy)tetrahydropyran (0.85 ml). The mixture was stirred at 70° C. for 7 hours. The reaction mixture was cooled to room temperature. (2-Pyridin-3-yl-ethyl)-pyridin-4-ylmethyl-amine (1.28 g), and N-ethyldiisopropylamine (1.3 ml) were added thereto. The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water and then saturated saline, and dried with anhydrous sodium sulfate. After condensation under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→4:1). The purified product was condensed under reduced pressure to give the title compound (236 mg) as a colorless oily matter. 
         [1454]      1 H-NMR (CDCl 3 ), δ ppm: 1.40-1.90 (7H, m), 2.51-2.83 (6H, m), 3.29-3.44 (1H, m), 3.44-3.54 (2H, m), 3.54-3.70 (2H, m), 3.69-3.90 (2H, m), 4.47-4.57 (1H, m), 7.12-7.23 (3H, m), 7.37-7.48 (1H, m), 8.38-8.53 (4H, m). 
       Reference Example 17 
     Synthesis of 3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propan-1-ol 
       [1455]    A 2N-hydrogen chloride methanol solution (1.2 ml) was added to a methanol solution (4 ml) of (2-pyridin-3-ylethyl)pyridin-4-ylmethyl-[3-(tetrahydropyran-2-yloxy)propyl]amine (236 mg). The mixture was stirred at room temperature overnight. A 2N-hydrogen chloride methanol solution (0.5 ml) was added thereto, and the mixture was further stirred at 50° C. for 3 hours. Triethylamine (0.64 ml) was added to the reaction mixture, and the mixture was condensed under reduced pressure. The residue was purified by basic silica gel column chromatography (dichloromethane). The purified product was condensed under reduced pressure to give the title compound (186.3 mg) as an orange oily matter. 
         [1456]      1 H NMR (CDCl 3 ), δ ppm: 1.66-1.88 (2H, m), 2.59-2.77 (4H, m), 2.77-2.88 (2H, m), 3.65 (2H, s), 3.68-3.84 (3H, m), 7.11-7.25 (3H, m), 7.42 (1H, d, J=7.8 Hz), 8.42 (1H, s), 8.43-8.47 (1H, m), 8.50-8.60 (2H, m). 
       Reference Example 18 
     Synthesis of (3-chloropropyl)-(2-pyridin-3-ylethyl)pyridin-4-ylmethylamine 
       [1457]    (2-Pyridin-3-yl-ethyl)-pyridin-4-ylmethyl-amine (210 mg) and N-ethyldiisopropylamine (0.34 ml) were added to a DMF solution (2 ml) of 1-chloro-3-iodopropane (0.16 ml). The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water and then saturated saline, and dried with anhydrous sodium sulfate. After condensation under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→4:1). The purified product was condensed under reduced pressure to give the title compound (74 mg) as a colorless oily matter. 
         [1458]      1 H-NMR (CDCl 3 ), δ ppm: 1.82-1.99 (2H, m), 2.61-2.82 (6H, m), 3.52 (2H, t, J=6.3 Hz), 3.61 (2H, s), 7.14 (2H, d, J=5.9 Hz), 7.19 (1H, dd, J=7.7, 4.8 Hz), 7.36-7.49 (1H, m), 8.38-8.56 (4H, m). 
       Reference Example 19 
     Synthesis of 2-nitro-N-(2-pyridin-3-ylethyl)benzenesulfonamide 
       [1459]    2-Nitrobenzene sulfonyl chloride (11.64 g) was added to a dichloromethane solution (100 ml) of 3-(2-aminoethyl)pyridine (6.11 g) and triethylamine (9 ml) at 0° C. The mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was crystallized from ethyl acetate to give the title compound (5.06 g) as a yellow powder. 
         [1460]      1 H NMR (DMSO-d 6 ), δ ppm: 2.76 (2H, t, J=7.1 Hz), 3.19 (2H, t, J=7.1 Hz), 7.26 (1H, dd, J=4.8 Hz, 7.8 Hz), 7.60 (1H, d, J=7.8 Hz), 7.8-8.0 (4H, m), 8.19 (1H, brs), 8.3-8.4 (2H, m). 
       Reference Example 20 
     Synthesis of (2-methylbenzyl)-(2-pyridin-3-ylethyl)amine 
       [1461]    The synthesis of the title compound was performed in the same manner as in Reference Example 15 using appropriate starting materials. 
         [1462]      1 H NMR (CDCl 3 ), δ ppm: 0.95-1.95 (1H, br-s), 2.30 (3H, s), 2.77-2.88 (2H, m), 2.91-3.02 (2H, m), 3.78 (2H, s), 7.06-7.30 (5H, m), 7.53 (1H, br-d, J=7.5 Hz), 8.41-8.53 (2H, m). 
       Reference Example 21 
     Synthesis of 6-(3-chloropropoxy)-1-methyl-1H-quinolin-2-one 
       [1463]    Potassium carbonate (0.829 g) was dissolved in acetonitrile (10 ml) and water (10 ml), and 6-hydroxy-2-methoxyquinoline (0.875 g) and 1-chloro-3-bromopropane (1.48 ml) was added thereto, and the mixture was stirred while heating under reflux for 4 hours. The reaction mixture was condensed under reduced pressure. Water was added to the residue, followed by extraction using ethyl acetate. The organic layer was dried with sodium sulfate, and was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1). The purified product was condensed to dryness under reduced pressure to give the title compound (1.107 g) as a white powder. 
         [1464]    1H-NMR (CDCl 3 ) δ ppm: 2.18-2.35 (2H, m), 3.71 (3H, s), 3.78 (2H, t, J=6.2 Hz), 4.18 (2H, t, J=5.9 Hz), 6.72 (1H, d, J=9.5 Hz), 7.03 (1H, d, J=2.8 Hz), 7.19 (1H, dd, J=9.2, 2.8 Hz), 7.30 (1H, d, J=9.2 Hz), 7.60 (1H, d, J=9.5 Hz). 
       Reference Example 22 
     Synthesis of 6-(3-aminopropoxy)-1-methyl-1H-quinolin-2-one 
       [1465]    Hydrazine hydrate (6.54 ml) was added to a ethanol solution (250 ml) of 2-[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]isoindole-1,3-dione (16.28 g), and stirred while heating under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure. A 1N-sodium hydroxide aqueous solution was added to the residue, and stirred for 30 minutes, and extraction with dichloromethane was performed. The organic layer was washed with water and a saturated sodium chloride aqueous solution, in this order. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (8.04 g) as a colorless oil. 1H-NMR (CDCl 3 ) δ ppm: 1.89-2.06 (2H, m), 2.95 (2H, t, J=6.8 Hz), 3.71 (3H, s), 4.11 (2H, t, J=6.1 Hz), 6.72 (1H, d, J=9.5 Hz), 7.02 (1H, d, J=2.8 Hz), 7.19 (1H, dd, J=9.2, 2.8 Hz), 7.30 (1H, J=9.2 Hz), 7.60 (1H, d, J=9.5 Hz). 
       Reference Example 23 
     Synthesis of 6-(2-iodoethoxy)-1-methyl-1H-quinolin-2-one 
       [1466]    The synthesis of the title compound was performed in the same manner as in Reference Example 9 using appropriate starting materials. 1H-NMR (CDCl 3 ) δ ppm: 3.45 (2H, t, J=6.6 Hz), 3.71 (3H, s), 4.31 (2H, t, J=6.6 Hz), 6.73 (1H, d, J=9.5 Hz), 7.02 (1H, d, J=2.8 Hz), 7.21 (1H, dd, J=9.2, 2.8 Hz), 7.31 (1H, d, J=9.2 Hz), 7.60 (1H, d, J=9.5 Hz). 
       Reference Example 24 
     Synthesis of 6-(2-aminoethoxy)-1-methyl-1H-quinolin-2-one 
       [1467]    The synthesis of the title compound was performed in the same manner as in Reference Example 22 using appropriate starting materials. 
         [1468]    1H-NMR (CDCl 3 ) δ ppm: 3.13 (2H, t, J=5.1 Hz), 3.71 (3H, s), 4.05 (2H, t, J=5.1 Hz), 6.72 (1H, d, J=9.5 Hz), 7.02 (1H, d, J=2.8 Hz), 7.21 (1H, dd, J=9.2, 2.8 Hz), 7.31 (1H, d, J=9.2 Hz), 7.60 (1H, d, J=9.5 Hz). 
       Reference Example 25 
     Synthesis of 2-nitro-N-{2-[4-(pyridin-3-ylmethoxy)piperidin-1-yl]ethyl}benzene sulfonamide 
       [1469]    The synthesis of the title compound was performed in the same manner as in Reference Example 19 using appropriate starting materials. 
         [1470]    1H-NMR (CDCl 3 ) δ ppm: 1.42-1.99 (4H, m), 2.13-2.35 (2H, m), 2.43-2.69 (4H, m), 3.21 (2H, t, J=6.0 Hz), 3.39-3.54 (1H, m), 4.52 (2H, s), 7.28 (1H, dd, J=7.9, 4.8 Hz), 7.63-7.70 (1H, m), 7.70-7.79 (2H, m), 7.83-7.89 (1H, m), 8.91-8.98 (1H, m), 8.53 (1H, dd, J=4.8, 1.6 Hz), 8.56 (1H, d, J=1.6 Hz). 
       Reference Example 26 
     Synthesis of 6-(4-aminobutoxy)-1-methyl-1H-quinolin-2-one 
       [1471]    The synthesis of the title compound was performed in the same manner as in Reference Example 22 using appropriate starting materials. 
         [1472]    1H-NMR (CDCl 3 ) δ ppm: 1.58-1.72 (2H, m), 1.81-1.98 (2H, m), 2.80 (2H, t, J=6.9 Hz), 3.71 (3H, s), 4.03 (2H, t, J=6.3 Hz), 6.71 (1H, d, J=9.5 Hz), 7.00 (1H, d, J=2.8 Hz), 7.18 (1H, dd, J=9.2, 2.8 Hz), 7.29 (1H, d, J=9.2 Hz), 7.59 (1H, d, J=9.5 Hz). 
       Reference Example 27 
     Synthesis of 6-(3-iodopropoxy)-1-methyl-3,4-dihydro-1H-quinolin-2-one 
       [1473]    The synthesis of the title compound was performed in the same manner as in Reference Example 9 using appropriate starting materials. 1H-NMR (CDCl 3 ) δ ppm: 2.16-2.32 (2H, m), 2.56-2.70 (2H, m), 2.87 (2H, t, J=6.7 Hz), 3.33 (3H, s), 3.31-3.45 (2H, m), 4.02 (2H, t, J=5.8 Hz), 6.75 (1H, d, J=2.8 Hz), 6.78 (1H, dd, J=8.7, 2.8 Hz), 6.89 (1H, d, J=8.7 Hz). 
       Reference Example 28 
     Synthesis of N-(3-imidazol-1-yl-propyl)-2-nitrobenzenesulfonamide 
       [1474]    The synthesis of the title compound was performed in the same manner as in Reference Example 19 using appropriate starting materials. 
         [1475]    1H-NMR (CDCl 3 ) δ ppm: 1.71-1.95 (2H, m), 2.85 (2H, t, J=6.8 Hz), 3.97 (2H, t, J=6.9 Hz), 6.86 (1H, s), 7.10 (1H, s), 7.55 (1H, s), 7.83-7.92 (2H, m), 7.92-8.02 (2H, m), 8.16 (1H, s). 
       Reference Example 30 
     Synthesis of N-(3-Chloropropyl)-N-(2-methylbenzyl)-N-(2-pyridin-3-ylethyl)amine 
       [1476]    The synthesis of the title compound was performed in the same manner as in Reference Example 18 using appropriate starting materials. 
         [1477]    1H-NMR (CDCl 3 ) δ ppm: 1.78-1.95 (2H, m), 2.26 (3H, s), 2.60-2.79 (6H, m), 3.50 (2H, t, J=6.5 Hz), 3.58 (2H, s), 7.08-7.24 (5H, m), 7.33-7.39 (1H, m), 8.36 (1H, d, J=1.7 Hz), 8.41 (1H, dd, J=4.8, 1.7 Hz). 
       Reference Example 31 
     Synthesis of 6-(3-iodopropoxy)-3,4-dihydro-2H-isoquinolin-1-one 
       [1478]    The synthesis of the title compound was performed in the same manner as in Reference Example 9 using appropriate starting materials. 1H-NMR (CDCl 3 ) δ ppm: 2.19-2.35 (2H, m), 2.97 (2H, t, J=6.6 Hz), 3.37 (2H, t, J=6.7 Hz), 3.50-3.62 (2H, m), 4.09 (2H, t, J=5.8 Hz), 5.98 (1H, s), 6.71 (1H, d, J=2.4 Hz), 6.86 (1H, dd, J=8.6, 2.4 Hz), 8.01 (1H, d, J=8.6 Hz). 
       Reference Example 32 
     Synthesis of 2-hydroxy-7,8-dihydro-6H-5-thia-8-aza-benzocyclohepten-9-one 
       [1479]    The synthesis of the title compound was performed in the same manner as in Reference Example 1 using appropriate starting materials. 1H-NMR (CD3OD) δ ppm: 3.06 (2H, t, J=6.0 Hz), 3.26 (2H, t, J=6.0 Hz), 6.85 (1H, dd, J=8.3, 2.8 Hz), 7.01 (1H, d, J=2.8 Hz), 7.34 (1H, d, J=8.3 Hz). 
       Example 1 
     Synthesis of 1-methyl-6-{5-[(2-methylbenzyl)-(2-pyridin-3-ylethyl)amino]pentyl oxy}-1H-quinolin-2-one dihydrochloride 
       [1480]    Potassium carbonate (360 mg) and (2-methylbenzyl)-(2-pyridin-3-ylethyl)amine (591 mg) were added to a DMF solution (6.5 ml) of 6-(5-bromopentyloxy)-1-methyl-1H-quinolin-2-one (650 mg). The mixture was stirred at 60° C. for 8 hours. Ice water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water and then saturated saline, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:ethyl acetate:methanol:aqueous ammonia=70:20:10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (1.0 ml) was added to an ethyl acetate solution (20 ml) of the residue, which was stirred at room temperature. The liquid was condensed to dryness under reduced pressure to give the title compound (270 mg) as a pale yellow amorphus solid. 
         [1481]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.32-1.50 (2H, m), 1.65-1.99 (4H, m), 2.47 (3H, s), 2.92-3.21 (2H, m), 3.21-3.50 (4H, m), 3.59 (3H, s), 3.88-4.09 (2H, m), 4.30-4.52 (2H, m), 6.61 (1H, d, J=9.4 Hz), 7.05-7.35 (5H, m), 7.46 (1H, d, J=9.2 Hz), 7.73 (1H, d, J=7.2 Hz), 7.84 (1H, d, J=9.6 Hz), 7.89-8.01 (1H, m), 8.40 (1H, br-d, J=7.8 Hz), 8.79 (1H, d, J=4.9 Hz), 8.89 (1H, s). 
       Example 2 
     Synthesis of N-[5-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)pentyl]-2-nitro-N-(2-pyridin-3-ylethyl)benzenesulfonamide 
       [1482]    2-Nitro-N-(2-pyridin-3-ylethyl)benzenesulfonamide (308 mg), and potassium carbonate (276 mg) were added to a DMF solution (5 ml) of 6-(5-bromopentyloxy)-1-methyl-1H-quinolin-2-one (348 mg). The mixture was stirred at room temperature for 2 hours. Ice water was poured to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate→ethyl acetate:methanol=10:1). The purified product was condensed to dryness under reduced pressure to give 5 the title compound (535 mg) as a yellow amorphus solid. 
         [1483]      1 H-NMR (CDCl 3 ) δ ppm: 1.4-1.9 (6H, m), 2.88 (2H, t, J=7.5 Hz), 3.40 (2H, t, J=7.5 Hz), 3.52 (2H, t, J=7.7 Hz), 3.71 (3H, s), 3.98 (2H, t, J=6.3 Hz), 6.71 (1H, d, J=9.5 Hz), 6.98 (1H, d, J=2.8 Hz), 7.1-7.3 (2H, m), 7.29 (1H, d, J=9.2 Hz), 7.4-7.7 (5H, m), 7.9-8.1 (1H, m), 8.40 (1H, d, J=1.8 Hz), 8.45 (1H, dd, J=1.8 Hz, 4.8 Hz). 
       Example 3 
     Synthesis of 1-methyl-6-[5-(2-pyridin-3-ylethylamino)pentyloxy]-1H-quinolin-2-one dihydrochloride 
       [1484]    Lithium hydroxide (102 mg), and thioglycolic acid (0.141 ml) were added to a DMF solution (5 ml) of N-[5-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)pentyl]-2-nitro-N-(2-pyridin-3-ylethyl)benzenesulfonamide (535 mg). The mixture was stirred at room temperature overnight. Ice water was poured to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water, dried with anhydrous sodium sulfate, and condensed under reduced pressure. A 1N-hydrogen chloride ethanol solution (1.0 ml), and ethyl acetate were added to the residue. The mixture was stirred at room temperature. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (108 mg) as a white powder. 
         [1485]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.4-1.6 (2H, m), 1.6-1.8 (4H, m), 2.8-3.0 (2H, m), 3.2-3.4 (4H, m), 3.60 (3H, s), 4.04 (2H, t, J=6.1 Hz), 4.0-4.8 (1H, br), 6.61 (1H, d, J=9.5 Hz), 7.25 (1H, dd, J=2.8 Hz, 9.2 Hz), 7.31 (1H, d, J=2.8 Hz), 7.46 (1H, d, J=9.2 Hz), 7.85 (1H, d, J=9.5 Hz), 8.05 (1H, dd, J=5.6 Hz, 8.1 Hz), 8.57 (1H, d, J=8.1 Hz), 8.84 (1H, d, J=5.6 Hz), 8.94 (1H, s), 9.36 (1H, brs). 
       Example 4 
     Synthesis of 1-methyl-6-[5-((2-methylbenzyl)-(2-[4-(pyridin-3-ylmethoxy)piperidin-1-yl]ethyl}amino)pentyloxy]-1H-quinolin-2-one trihydrochloride 
       [1486]    Methane sulfonyl chloride (0.59 ml) was added to a dichloromethane solution (30 ml) of 6-{5-[(2-hydroxyethyl)-(2-methylbenzyl)amino]pentyloxy}-1-methyl-1H-quinolin-2-one (2.83 g) and N-ethyldiisopropylamine (1.81 ml). The mixture was stirred at room temperature for an hour. Water was added to the reaction mixture, followed by extraction using dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was dissolved in acetonitrile (50 ml). Sodium iodide (1.56 g), 3-(piperidin-4-yloxymethyl)pyridine (1.46 g) and N-ethyldiisopropylamine (3.61 ml) were added thereto, and the mixture was stirred at 60° C. for 3 hours. The reaction mixture was condensed under reduced pressure. Water was added to the residue, followed by extraction using dichloromethane. The organic layer was washed with water and then saturated saline, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:ethyl acetate:methanol:aqueous ammonia=70:20:10:1). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride ethanol solution (0.41 ml) was added to an isopropyl alcohol solution of the residue. The mixture was stirred at room temperature. The liquid was condensed to dryness under reduced pressure to give the title compound (2.41 g) as a white amorphous solid. 
         [1487]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.4-1.6 (2H, m), 1.7-2.3 (8H, m), 2.46 (3H, s), 3.0-3.9 (11H, m), 3.60 (3H, s), 4.02 (2H, t, J=6.2 Hz), 4.46 (2H, s), 4.75 (2H, s), 6.62 (1H, d, J=9.5 Hz), 7.2-7.4 (5H, m), 7.47 (1H, d, J=9.2 Hz), 7.73 (1H, d, J=7.5 Hz), 7.86 (1H, d, J=9.5 Hz), 8.04 (1H, dd, J=5.7 Hz, 8.0 Hz), 8.5-8.6 (1H, br), 8.85 (1H, d, J=5.7 Hz), 8.94 (1H, brs), 10.2-11.8 (2H, br). 
       Example 5 
     Synthesis of 6-{(5-[cyclohexylmethyl-(2-pyridin-3-ylethyl)amino]pentyloxy}-1-methyl-1H-quinolin-2-one dihydrochloride 
       [1488]    Triethylamine (0.15 ml) was added to a 1,2-dichloroethane solution (2.5 ml) of 1-methyl-6-[5-(2-pyridin-3-ylethylamino)pentyloxy]-1H-quinolin-2-one dihydrochloride (219 mg). The mixture was stirred at room temperature for 30 minutes. Cyclohexane carboxaldehyde (0.073 ml) and sodium triacetoxyborohydrate (159 mg) were added thereto, and the mixture was stirred at room temperature overnight. A saturated sodium hydrogencarbonate aqueous solution was added to the reaction mixture, followed by extraction using dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:1). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride ethanol solution (1.0 ml) was added to an ethanol solution (20 ml) of the residue, which was stirred at room temperature. The reaction mixture was condensed under reduced pressure and ethyl acetate was added to the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (100 mg) as a pale yellow powder. 
         [1489]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.8-1.4 (6H, m), 1.5-2.0 (11H, m), 2.9-3.6 (8H, m), 3.59 (3H, s), 4.0-4.5 (1H, br), 4.06 (2H, t, J=6.1 Hz), 6.61 (1H, d, J=9.5 Hz), 7.25 (1H, dd, J=2.8 Hz, 9.2 Hz), 7.31 (1H, d, J=2.8 Hz), 7.46 (1H, d, J=9.2 Hz), 7.84 (1H, d, J=9.5 Hz), 8.01 (1H, dd, J=5.6 Hz, 8.1 Hz), 8.53 (1H, J=8.1 Hz), 8.83 (1H, d, J=5.6 Hz), 8.95 (1H, s), 10.4 (1H, brs). 
       Example 6 
     Synthesis of 6-{5-[(2,6-dichlorobenzyl)-(2-pyridin-3-ylethyl)amino]pentyloxy}-1-methyl-1H-quinolin-2-one dihydrochloride 
       [1490]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1491]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.6 (2H, m), 1.7-2.0 (4H, m), 3.0-3.7 (8H, m), 3.58 (3H, s), 4.02 (2H, t, J=6.0 Hz), 4.0-5.0 (1H, br), 6.59 (1H, d, J=9.5 Hz), 7.22 (1H, dd, J=2.8 Hz, 9.1 Hz), 7.27 (1H, d, J=2.8 Hz), 7.44 (1H, d, J=9.1 Hz), 7.4-7.7 (3H, m), 7.82 (1H, d, J=9.5 Hz), 7.8-8.0 (1H, m), 8.38 (1H, d, J=7.7 Hz), 8.76 (1H, d, J=5.3 Hz), 9.02 (1H, s), 9.9-10.2 (1H, br). 
       Example 7 
     Synthesis of 6-{5-[isobutyl-(2-pyridin-3-ylethyl)amino]pentyloxy}-1-methyl-1H-quinolin-2-one dihydrochloride 
       [1492]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
       Example 8 
     Synthesis of 6-{5-[cyclohexyl-(2-pyridin-3-ylethyl)amino]pentyloxy}-1-methyl-1 H-quinolin-2-one dihydrochloride 
       [1493]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
       Example 9 
     Synthesis of 6-{5-[benzyl-(2-pyridin-3-ylethyl)amino]pentyloxy}-1-methyl-1H-quinolin-2-one dihydrochloride 
       [1494]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1495]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.5 (2H, m), 1.7-2.0 (4H, m), 3.0-3.2 (2H, m), 3.3-3.5 (4H, m), 3.59 (3H, s), 4.03 (2H, t, J=6.2 Hz), 4.3-4.6 (2H, m), 4.0-4.5 (1H, br), 6.61 (1H, d, J=9.5 Hz), 7.24 (1H, dd, J=2.8 Hz, 9.1 Hz), 7.29 (1H, d, J=2.8 Hz), 7.4-7.5 (4H, m), 7.6-7.8 (2H, m), 7.83 (1H, d, J=9.5 Hz), 7.90 (1H, dd, J=5.3 Hz, 8.1 Hz), 8.35 (1H, d, J=8.1 Hz), 8.78 (1H, d, J=5.3 Hz), 8.85 (1H, s), 11.22 (1H, brs). 
       Example 10 
     Synthesis of 1-methyl-6-{5-[(2-pyridin-3-ylethyl)-o-tolylamino]pentyloxy}-1H-quinolin-2-one dihydrochloride 
       [1496]    1-Methyl-6-[5-(2-pyridin-3-ylethylamino)pentyloxy]-1H-quinolin-2-one (183 mg), 2-bromotoluene (0.072 ml), palladium acetate (II) (5.6 mg), tri-tert-butylphosphine tetrafluoroborate (8 mg), and sodium t-butoxide (0.19 ml) were added to toluene (1 ml). The mixture was heated under reflux for 8 hours under nitrogen atmosphere. After the reaction, the precipitate was removed from the reaction mixture by celite filtration. Water was added thereto, followed by extraction using dichloromethane. The organic layer was washed with water and then saturated saline, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate→ethyl acetate:methanol=20:1). The purified product was condensed under reduced pressure to give the title compound (93 mg) as a yellow oily matter. 
         [1497]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.2-1.5 (2H, m), 1.6-1.9 (2H, m), 2.0-2.2 (2H, m), 2.50 (3H, s), 2.7-3.5 (6H, m), 3.59 (3H, s), 3.96 (2H, t, J=6.3 Hz), 4.0-5.0 (2H, br), 6.59 (1H, d, J=9.5 Hz), 7.0-7.4 (6H, m), 7.44 (1H, d, J=9.1 Hz), 7.82 (1H, d, J=9.5 Hz), 7.9-8.0 (1H, m), 8.3-8.4 (1H, m), 8.7-8.8 (2H, m). 
       Example 11 
     Synthesis of 1-methyl-6-{5-[(3-phenylpropyl)-(2-pyridin-3-ylethyl)amino]pentyl oxy}-1H-quinolin-2-one dihydrochloride 
       [1498]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1499]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.5 (2H, m), 1.6-1.9 (4H, m), 2.0-2.2 (2H, m), 2.63 (2H, t, J=7.7 Hz), 3.0-3.5 (8H, m), 3.59 (3H, s), 3.8-4.2 (3H, m), 6.60 (1H, d, J=9.5 Hz), 7.1-7.4 (7H, m), 7.46 (1H, d, J=9.2 Hz), 7.84 (1H, d, J=9.5 Hz), 7.97 (1H, dd, J=5.3 Hz, 8.1 Hz), 8.48 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=5.3 Hz), 8.92 (1H, s), 11.04 (1H, brs). 
       Example 12 
     Synthesis of 4-{[[5-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)pentyl]-(2-pyridin-3-ylethyl)amino]methyl}benzoic acid methyl ester dihydrochloride 
       [1500]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1501]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.5 (2H, m), 1.6-1.9 (4H, m), 3.0-3.2 ( 2 H, m), 3.2-3.5 (4H, m), 3.58 (3H, s), 3.85 (3H, s), 4.00 (2H, t, J=6.3 Hz), 4.3-4.6 (2H, m), 4.5-5.5 (1H, br), 6.59 (1H, d, J=9.5 Hz), 7.22 (1H, dd, J=2.8 Hz, 9.2 Hz), 7.27 (1H, d, J=2.8 Hz), 7.44 (1H, d, J=9.2 Hz), 7.82 (1H, d, J=9.5 Hz), 7.86 (2H, d, J=8.3 Hz), 7.9-8.0 (1H, m), 7.99 (2H, d, J=8.3 Hz), 8.42 (1H, d, J=8.2 Hz), 8.79 (1H, d, J=5.5 Hz), 8.88 (1H, s), 11.50 (1H, brs). 
       Example 13 
     Synthesis of 4-{[[5-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)pentyl]-(2-pyridin-3-ylethyl)amino]methyl}benzoic acid 
       [1502]    A 1N-sodium hydroxide aqueous solution (0.72 ml) was added to a methanol solution (2 ml) of 4-{[[5-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)pentyl]-(2-pyridin-3-ylethyl)amino]methyl}benzoic acid methyl ester (153 mg). The mixture was stirred at 50° C. for 3 hours. The reaction mixture was condensed under reduced pressure. Water was added to the residue, and acetic acid was added for neutralization. The mixture was extracted using dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. Diisopropyl ether was added to the residue. The generated insoluble matter was separated by filtration and dried to give the title compound (115 mg) as a white powder. 
         [1503]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.2-1.5 (4H, m), 1.6-1.8 (2H, m), 2.3-2.6 (2H, m), 2.6-2.8 (4H, m), 3.59 (3H, s), 3.67 (2H, s), 3.96 (2H, t, J=6.4 Hz), 6.59 (1H, d, J=9.5 Hz), 7.1-7.3 (3H, m), 7.33 (2H, d, J=8.2 Hz), 7.44 (1H, d, J=9.1 Hz), 7.5-7.6 (1H, m), 7.7-7.9 (3H, m), 8.1-8.3 (2H, m), 12.5-13.0 (1H, br). 
       Example 14 
     Synthesis of 1-methyl-6-{5-[(2-methylbenzyl)pyridin-3-ylmethylamino]pentyloxy}-1H-quinolin-2-one dihydrochloride 
       [1504]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1505]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.5 (2H, m), 1.6-1.8 (2H, m), 1.8-2.0 (2H, m), 2.35 (3H, s), 3.0-3.2 (2H, m), 3.60 (3H, s), 3.9-4.1 (2H, m), 4.2-5.7 (5H, m), 6.61 (1H, d, J=9.5 Hz), 7.1-7.4 (5H, m), 7.46 (1H, d, J=9.2 Hz), 7.75 (1H, d, J=7.3 Hz), 7.85 (1H, d, J=9.5 Hz), 7.99 (1H, dd, J=5.4 Hz, 7.9 Hz), 8.85 (1H, d, J=7.9 Hz), 8.91 (1H, d, J=5.4 Hz), 9.21 (1H, s), 11.64 (1H, brs). 
       Example 15 
     Synthesis of 1-methyl-6-{5-[(3-phenylpropyl)pyridin-3-ylmethylamino]pentyloxy}-1H-quinolin-2-one dihydrochloride 
       [1506]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1507]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.3-1.5 (2H, m), 1.6-1.9 (4H, m), 1.9-2.2 (2H, m), 2.61 (2H, t, J=7.5 Hz), 2.9-3.2 (4H, m), 3.59 (3H, s), 4.02 (2H, t, J=6.2 Hz), 4.0-5.0 (3H, m), 6.61 (1H, d, J=9.5 Hz), 7.1-7.4 (7H, m), 7.46 (1H, d, J=9.2 Hz), 7.85 (1H, d, J=9.5 Hz), 7.9-8.1 (1H, m), 8.77 (1H, d, J=7.9 Hz), 8.92 (1H, d, J=5.0 Hz), 9.18 (1H, s), 11.71 (1H, brs). 
       Example 16 
     Synthesis of 6-[5-(bis{pyridin-3-ylmethyl]amino)pentyloxy}-1-methyl-1H-quinolin-2-one 
       [1508]    Pyridine-3-carbaldehyde (0.076 ml) was added to a 1,2-dichloroethane solution (3 ml) of 1-methyl-6-{5-[(pyridin-3-ylmethyl)-amino]-pentyloxy}-1H-quinolin-2-one (237 mg). The mixture was stirred for 30 minutes at room temperature. Sodium triacetoxyborohydride (0.23 g) was added to the mixture, and the mixture was stirred at room temperature for 3 days. A saturated sodium hydrogencarbonate aqueous solution was added to the reaction mixture, followed by extraction using dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:hexane=1:1). The purified product was condensed under reduced pressure to give the title compound (247 mg) as a yellow oil. 
         [1509]      1 H-NMR (CDCl 3 ) δ ppm: 1.3-1.8 (6H, m), 2.47 (2H, t, J=6.8 Hz), 3.58 (4H, s), 3.71 (3H, s), 3.95 (2H, t, J=6.4 Hz), 6.70 (1H, d, J=9.5 Hz), 6.98 (1H, d, J=2.8 Hz), 7.16 (1H, dd, J=2.8 Hz, 9.2 Hz), 7.2-7.4 (3H, m), 7.60 (1H, d, J=9.5 Hz), 7.6-7.7 (2H, m), 8.49 (2H, dd, J=1.6 Hz, 4.8 Hz), 8.57 (2H, d, J=1.7 Hz). 
       Example 17 
     Synthesis of 1-methyl-6-{5-[(2-methylbenzyl)pyridin-3-ylamino]pentyloxy}-1H-quinolin-2-one 
       [1510]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1511]      1 H-NMR (CDCl 3 ) δ ppm: 1.5-1.7 (2H, m), 1.8-1.9 (4H, m), 2.32 (3H, s), 3.45 (2H, t, J=7.6 Hz), 3.71 (3H, s), 4.01 (2H, t, J=6.3 Hz), 4.46 (2H, s), 6.72 (1H, d, J=9.5 Hz), 6.8-6.9 (1H, m), 6.98 (1H, d, J=2.8 Hz), 7.0-7.3 (6H, m), 7.29 (1H, d, J=9.2 Hz), 7.59 (1H, d, J=9.5 Hz), 7.92 (1H, dd, J=1.2 Hz, 4.6 Hz), 8.09 (1H, d, J=3.0 Hz). 
       Example 18 
     Synthesis of 1-methyl-6-{5-[(3-phenylpropyl)pyridin-3-ylamino]pentyloxy}-1H-quinolin-2-one 
       [1512]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1513]      1 H-NMR (CDCl 3 ) δ ppm: 1.4-1.7 (4H, m), 1.8-2.1 (4H, m), 2.66 (2H, t, J=7.7 Hz), 3.2-3.4 (4H, m), 3.70 (3H, s), 4.00 (2H, t, J=6.3 Hz), 6.71 (1H, d, J=9.5 Hz), 6.8-6.9 (1H, m), 6.98 (1H, d, J=2.8 Hz), 7.05 (1H, dd, J=4.6 Hz, 8.6 Hz), 7.1-7.4 (7H, m), 7.58 (1H, d, J=9.5 Hz), 7.88 (1H, dd, J=1.2 Hz, 4.5 Hz), 8.04 (1H, d, J=3.0 Hz). 
       Example 19 
     Synthesis of 1-methyl-6-{5-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]pentyloxy}-1H-quinolin-2-one trihydrochloride 
       [1514]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1515]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.80-2.02 (6H, m), 3.05-3.25 (2H, m), 3.36-3.52 (4H, m), 3.60 (3H, s), 3.97-4.10 (2H, m), 4.82 (2H, s), 6.61 (1H, d, J=9.5 Hz), 7.25 (1H, dd, J=9.1, 2.8 Hz), 7.32 (1H, d, J=2.8 Hz), 7.46 (1H, d, J=9.1 Hz), 7.86 (1H, d, J=9.5 Hz), 8.06 (1H, dd, J=8.1, 5.7 Hz), 8.53 (2H, d, J=6.3 Hz), 8.59 (1H, d, J=8.1 Hz), 8.86 (1H, d, J=5.7 Hz), 8.88 (1H, s), 9.04 (2H, d, J=6.3 Hz). 
       Example 20 
     Synthesis of 1-Methyl-6-{2-[(2-pyridin-3-ylethyl)pyridin-3-ylmethylamino]ethoxy}-1H-quinolin-2-one 
       [1516]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1517]      1 H-NMR (CDCl 3 ) δ: 2.78-2.91 (4H, m), 3.00 (2H, t, J=5.6 Hz), 3.69 (3H, s), 3.79 (2H, s), 4.04 (2H, t, J=5.6 Hz), 6.70 (1H, d, J=9.5 Hz), 6.63 (1H, d, J=2.8 Hz), 7.15-7.30 (4H, m), 7.41-7.50 (1H, m), 7.57-7.60 (2H, m), 8.42-8.53 (4H, m). 
       Example 21 
     Synthesis of 1-methyl-6-{2-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]ethoxy}-1H-quinolin-2-one 
       [1518]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1519]      1 H-NMR (CDCl 3 ) δ ppm: 2.79-2.91 (4H, m), 3.01 (2H, t, J=5.6 Hz), 3.70 (3H, s), 3.79 (2H, s), 4.05 (2H, t, J=5.6 Hz), 6.71 (1H, d, J=9.5 Hz), 6.93 (1H, d, J=2.8 Hz), 7.11-7.20 (4H, m), 7.27-7.30 (1H, m), 7.41-7.48 (1H, m), 7.58 (1H, d, J=9.5 Hz), 8.43-8.49 (4H, m). 
       Example 22 
     Synthesis of 1-methyl-6-[3-(pyridin-4-ylmethylpyridin-3-ylmethylamino)propoxy]-1H-quinolin-2-one trihydrochloride 
       [1520]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1521]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.86-2.19 (2H, m), 3.61 (3H, s), 3.71-5.00 (8H, m), 6.62 (1H, d, J=9.5 Hz), 7.09 (1H, dd, J=9.2, 2.8 Hz), 7.20 (1H, d, J=2.8 Hz), 7.44 (1H, d, J=9.2 Hz), 7.84 (1H, d, J=9.5 Hz), 7.80-7.94 (1H, m), 8.02-8.12 (2H, m), 8.52 (1H, d, J=7.3 Hz), 8.73-8.83 (3H, m), 8.93 (1H, s). 
       Example 23 
     Synthesis of 1-methyl-6-[4-(pyridin-4-ylmethylpyridin-3-ylmethylamino)butoxy]-1H-quinolin-2-one trihydrochloride 
       [1522]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1523]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.61-1.98 (4H, m), 2.60-3.00 (2H, m), 3.60 (3H, s), 3.23-5.11 (6H, m), 6.61 (1H, d, J=9.5 Hz), 7.18 (1H, dd, J=9.2, 2.9 Hz), 7.24 (1H, d, J=2.9 Hz), 7.46 (1H, d, J=9.2 Hz), 7.84 (1H, d, J=9.5 Hz), 7.89-8.00 (1H, m), 8.11-8.26 (2H, m), 8.64 (1H, d, J=7.8 Hz), 8.84 (1H, d, J=4.5 Hz), 8.88 (2H, d, J=6.4 Hz), 9.02 (1H, s). 
       Example 24 
     Synthesis of 1-methyl-6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one 
       [1524]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1525]      1 H-NMR (CDCl 3 ) δ ppm: 1.88-1.96 (2H, m), 2.68-2.81 (6H, m), 3.66 (2H, s), 3.71 (3H, s), 3.93 (2H, t, J=6.0 Hz), 6.73 (1H, d, J=9.5 Hz), 6.92 (1H, d, J=2.8 Hz), 7.09-7.16 (4H, m), 7.28-7.31 (1H, m), 7.39-7.46 (1H, m), 7.62 (1H, d, J=9.5 Hz), 8.41-8.46 (4H, m). 
       Example 25 
     Synthesis of 1-Methyl-6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-1H-quinolin-2-one 
       [1526]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1527]      1 H-NMR (CDCl 3 ) δ ppm: 1.85-1.91 (2H, m), 2.60-2.88 (10H, m), 3.33 (3H, s), 3.64 (2H, s), 3.88 (2H, t, J=6.0 Hz), 6.64-6.71 (2H, m), 6.89 (1H, d, J=8.7 Hz), 7.13-7.19 (2H, m), 7.30-7.33 (1H, m), 7.35-7.46 (1H, m), 8.40-8.52 (3H, m), 8.53 (1H, d, J=1.2 Hz). 
       Example 26 
     Synthesis of (2-pyridin-3-ylethyl)pyridin-4-ylmethyl-[3-(quinolin-6-yloxy)propyl]amine 
       [1528]    The synthesis of the title compound was performed in the same manner as in Example 16 using appropriate starting materials. 
         [1529]      1 H-NMR (CDCl 3 ) δ ppm: 1.93-2.02 (2H, m), 2.71-2.80 (6H, m), 3.66 (2H, s), 4.02 (2H, t, J=6.1 Hz), 6.989 (1H, d, J=2.8 Hz), 7.09-7.18 (3H, m), 7.28-7.39 (3H, m), 7.98-8.06 (2H, m), 8.43-8.45 (4H, m), 8.77-8.78 (1H, m). 
       Example 27 
     Synthesis of 1-methyl-5-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1530]    (2-Pyridin-3-ylethyl)pyridin-4-ylmethylamine (128 mg), and N-ethyldiisopropylamine (0.13 ml) were added to a DMF solution (5 ml) of 5-(3-iodopropoxy)-1-methyl-1H-quinolin-2-one (172 mg). The mixture was stirred at 60° C. for 3.5 hours. The reaction mixture was added to ice water, followed by extraction using ethyl acetate. The organic layer was washed with water and then saturated saline, dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1→1:1). 
         [1531]    The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution was added to an ethyl acetate solution of the residue, which was stirred at room temperature. The generated insoluble matter was separated by filtration and dried to give the title compound (21 mg) as a white powder. 
         [1532]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.26-2.54 (2H, m), 3.00-5.29 (10H, m), 3.60 (3H, s), 6.56 (1H, d, J=9.7 Hz), 6.83 (1H, d, J=8.2 Hz), 7.12 (1H, d, J=8.6 Hz), 7.51-7.60 (1H, m), 7.92 (1H, d, J=9.7 Hz), 8.02 (1H, dd, J=8.0, 5.5 Hz), 8.24-8.40 (2H, m), 8.54 (1H, d, J=8.0 Hz), 8.84 (1H, d, J=5.5 Hz), 8.92 (2H, d, J=5.6 Hz), 8.95 (1H, s). 
       Example 28 
     Synthesis of 1-methyl-7-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1533]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [1534]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.14-2.43 (2H, m), 2.88-4.95 (10H, m), 3.59 (3H, s), 6.44 (1H, d, J=9.4 Hz), 6.85 (1H, d, J=8.6 Hz), 6.89 (1H, s), 7.65 (1H, d, J=8.6 Hz), 7.83 (1H, d, J=9.4 Hz), 7.97 (1H, dd, J=8.0, 5.6 Hz), 8.07-8.24 (2H, m), 8.47 (1H, d, J=8.0 Hz), 8.81 (1H, d, J=5.6 Hz), 8.86 (2H, d, J=5.6 Hz), 8.90 (1H, s). 
       Example 29 
     Synthesis of 1-methyl-8-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1535]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [1536]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.30-2.55 (2H, m), 3.25-3.60 (6H, m), 3.77 (3H, s), 4.09-4.29 (2H, m), 4.54-5.00 (2H, m), 6.60 (1H, d, J=9.4 Hz), 7.16-7.28 (2H, m), 7.31 (1H, dd, J=6.8, 2.3 Hz), 7.84 (1H, d, J=9.4 Hz), 8.04 (1H, dd, J=8.1, 5.4 Hz), 8.32-8.46 (2H, m), 8.56 (1H, d, J=8.1 Hz), 8.85 (1H, d, J=5.4 Hz), 8.91-9.02 (3H, m). 
       Example 30 
     Synthesis of 6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1537]    The synthesis of the title compound was performed in the same manner as in Example 27 using appropriate starting materials. 
         [1538]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.18-2.40 (2H, m), 3.15-3.56 (6H, m), 3.95-4.16 (2H, m), 4.59-4.87 (2H, m), 6.51 (1H, d, J=9.5 Hz), 7.12 (1H, dd, J=8.9, 2.7 Hz), 7.20 (1H, d, J=2.7 Hz), 7.28 (1H, d, J=8.9 Hz), 7.86 (1H, d, J=9.5 Hz), 8.03 (1H, dd, J=8.1, 5.4 Hz), 8.31-8.44 (2H, m), 8.55 (1H, d, J=8.1 Hz), 8.84 (1H, d, J=5.4 Hz), 8.93-9.03 (3H, m). 
       Example 31 
     Synthesis of 1-methyl-4-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1539]    Triphenyl phosphine (102 mg) and diethyl azodicarboxylate (68 mg) were added to a tetrahydrofuran (THF) solution (5 ml) of 4-hydroxy-1-methyl-1H-quinolin-2-one (63 mg), and 3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propane-1-ol (81.4 mg). The mixture was stirred overnight. After the reaction mixture was condensed under reduced pressure, the residue was purified by silica gel column chromatography (dichloromethane:methanol=20:1→10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.29 ml) was added to an ethyl acetate solution of the residue, which was stirred at room temperature for 30 minutes. The generated insoluble matter was separated by filtration, and dried to give the title compound (126.8 mg) as a white powder. 
         [1540]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.29-2.56 (2H, m), 3.11-3.61 (6H, m), 3.56 (3H, s), 4.11-4.30 (2H, m), 4.50-4.94 (2H, m), 6.03 (1H, s), 7.32-7.41 (1H, m), 7.52 (1H, d, J=8.4 Hz), 7.62-7.76 (2H, m), 8.10 (1H, dd, J=8.0, 5.3 Hz), 8.21-8.34 (2H, m), 8.53 (1H, d, J=8.0 Hz), 8.83 (1H, d, J=5.3 Hz), 8.90 (2H, d, J=5.7 Hz), 8.94 (1H, s). 
       Example 32 
     Synthesis of 6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-2H-isoquinolin-1-one trihydrochloride 
       [1541]    Triphenyl phosphine (51 mg) and di-tert-butyl azodicarboxylate (45 mg) were added to a tetrahydrofuran (THF) solution (1.5 ml) of 6-hydroxy-2H-isoquinolin-1-one (29 mg), and 3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propan-1-ol (40 mg). The mixture was stirred overnight. After the reaction mixture was condensed under reduced pressure, the residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→4:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.06 ml) was added to an ethyl acetate solution of the residue, which was stirred at room temperature for 30 minutes. The generated insoluble matter was separated by filtration, and was dried to produce the title compound (31.4 mg) as a white powder. 
         [1542]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.14-2.45 (2H, m), 2.91-3.78 (6H, m), 4.08-4.25 (2H, m), 4.37-4.81 (2H, m), 6.46 (1H, d, J=7.1 Hz), 6.99 (1H, dd, J=8.8, 2.2 Hz), 7.08 (1H, d, J=2.2 Hz), 7.10-7.18 (1H, m), 7.92 (1H, dd, J=8.0, 5.5 Hz), 7.99-8.14 (2H, m), 8.08 (1H, d, J=8.8 Hz), 8.41 (1H, d, J=8.0 Hz), 8.78 (1H, d, J=5.5 Hz), 8.83 (2H, d, J=5.8 Hz), 8.87 (1H, s), 10.98-11.17 (1H, m). 
       Example 33 
     Synthesis of 2-methyl-6-{(3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-2H-isoquinolin-1-one trihydrochloride 
       [1543]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1544]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.09-2.41 (2H, m), 2.85-3.44 (6H, m), 3.47 (3H, s), 4.08-4.26 (2H, m), 4.26-4.66 (2H, m), 6.52 (1H, d, J=7.3 Hz), 6.99 (1H, dd, J=8.9, 2.3 Hz), 7.07 (1H, d, J=2.3 Hz), 7.44 (1H, d, J=7.3 Hz), 7.72 (1H, dd, J=7.6, 5.3 Hz), 7.81-7.92 (2H, m), 8.11 (1H, d, J=8.9 Hz), 8.11-8.19 (1H, m), 8.67 (1H, dd, J=5.3, 1.2 Hz), 8.69-8.76 (3H, m). 
       Example 34 
     Synthesis of 1,3-dimethyl-6-[3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy]-3,4-dihydro-1H-quinazolin-2-one trihydrochloride 
       [1545]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1546]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.08-2.38 (2H, m), 2.88 (3H, s), 3.16 (3H, s), 3.08-3.56 (6H, m), 3.92-4.05 (2H, m), 4.32 (2H, s), 4.42-4.85 (2H, m), 6.73 (1H, br-s), 6.70-6.90 (2H, m), 7.98 (1H, d-d, J=5.5, 8.1 Hz), 8.04-8.28 (2H, m), 8.46 (1H, d, J=8.1 Hz), 8.81 (1H, d, J=5.5 Hz), 8.81-8.98 (3H, m). 
       Example 35 
     Synthesis of 6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-isoquinolin-1-one trihydrochloride 
       [1547]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1548]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.13-2.40 (2H, m), 2.86 (2H, t, J=6.5 Hz), 3.10-3.57 (8H, m), 4.00-4.15 (2H, m), 4.55-4.81 (2H, m), 6.74-6.88 (2H, m), 7.66-7.80 (2H, m), 8.01 (1H, d-d, J=5.0, 8.0 Hz), 8.19-8.40 (2H, m), 8.52 (1H, d, J=8.0 Hz), 8.83 (1H, d, J=5.0 Hz), 8.85-9.00 (3H, m). 
       Example 36 
     Synthesis of 5-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-2,3-dihydro-isoindol-1-one trihydrochloride 
       [1549]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1550]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.15-2.43 (2H, m), 3.00-3.58 (6H, m), 3.96-4.16 (2H, m), 4.32 (2H, s), 4.44-4.83 (2H, m), 6.96 (1H, d-d, J=1.9, 8.3 Hz), 7.07 (1H, s), 7.57 (1H, d, J=8.3 Hz), 7.92-8.05 (1H, m), 8.10-8.40 (3H, m), 8.41-8.55 (1H, m), 8.78-9.00 (4H, m). 
       Example 37 
     Synthesis of N-ethyl-4-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}benzamide trihydrochloride 
       [1551]    1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC)(95 mg), and 1-hydroxy benzotriazole (HOBt)(66 mg) were added to a DMF solution (4 ml) of 4-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}benzoic acid (149 mg), ethyl amine hydrochloride (38 mg), and triethylamine (0.08 ml). The mixture was stirred at room temperature overnight. The reaction mixture was added to ice water. A 1N-sodium hydroxide aqueous solution was added thereto, followed by extraction using ethyl acetate. The organic layer was washed with water and then was dried with anhydrous sodium sulfate, followed by condensation under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1→4:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.16 ml) was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (80 mg) as a white powder. 
         [1552]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.11 (3H, t, J=7.2 Hz), 2.10-2.38 (2H, m), 2.89-3.57 (8H, m), 3.95-4.20 (2H, m), 4.28-4.69 (2H, m), 6.92 (2H, d, J=8.8 Hz), 7.75 (1H, dd, J=7.8, 5.2 Hz), 7.82 (2H, d, J=8.8 Hz), 7.83-7.94 (2H, m), 8.18 (1H, d, J=7.8 Hz), 8.35 (1H, t, J=5.4 Hz), 8.68 (1H, dd, J=5.2, 1.3 Hz), 8.71-8.79 (3H, m). 
       Example 38 
     Synthesis of 2-methyl-6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-isoquinolin-1-one trihydrochloride 
       [1553]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1554]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.10-2.40 (2H, m), 2.74-3.62 (10H, m), 2.99 (3H, s), 3.74-4.20 (2H, m), 4.39-4.82 (2H, m), 6.77 (1H, s), 6.82 (1H, d, J=8.6 Hz), 7.79 (1H, d, J=8.6 Hz), 7.87-8.00 (1H, m), 8.05-8.22 (2H, m), 8.46 (1H, d, J=8.2 Hz), 8.71-8.92 (4H, m). 
       Example 39 
     Synthesis of [3-(2-methyl-1,1-dioxo-2,3-dihydrobenzo[d]isothiazol-5-yloxy)propyl]-(2-pyridin-3-ylethyl)pyridin-4-ylmethylamine trihydrochloride 
       [1555]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1556]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.08-2.39 (2H, m), 2.79 (3H, s), 2.88-3.58 (6H, m), 4.00-4.20 (2H, m), 4.29-4.65 (2H, m), 4.35 (2H, s), 7.02-7.11 (2H, m), 7.70-7.81 (2H, m), 7.81-7.93 (2H, m), 8.18 (1H, d, J=8.1 Hz), 8.68 (1H, dd, J=5.2, 1.2 Hz), 8.70-8.79 (3H, m). 
       Example 40 
     Synthesis of 1-methyl-6-[3-(phenethylpyridin-4-ylmethylamino)propoxy]-1H-quinolin-2-one dihydrochloride 
       [1557]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1558]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.10-2.40 (2H, m), 2.79-3.70 (6H, m), 3.60 (3H, s), 3.99-4.19 (2H, m), 4.30-4.61 (2H, m), 6.62 (1H, d, J=9.5 Hz), 7.15-7.36 (7H, m), 7.47 (1H, d, J=9.2 Hz), 7.68-7.80 (2H, m), 7.84 (1H, d, J=9.5 Hz), 8.67 (2H, d, J=4.9 Hz). 
       Example 41 
     Synthesis of 1-methyl-6-{3-[(2-pyridin-2-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1559]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1560]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.12-2.31 (2H, m), 3.07-3.29 (2H, m), 3.33-3.59 (4H, m), 3.60 (3H, s), 3.95-4.19 (2H, m), 4.53 (2H, s), 6.62 (1H, J=9.5 Hz), 7.17 (1H, dd, J=9.2, 2.7 Hz), 7.25 (1H, d, J=2.7 Hz), 7.46 (1H, d, J=9.2 Hz), 7.58-7.67 (1H, m), 7.72 (1H, d, J=7.9 Hz), 7.85 (1H, d, J=9.5 Hz), 8.04 (2H, d, J=6.2 Hz), 8.11-8.21 (1H, m), 8.67 (1H, d, J=4.7 Hz), 8.80 (2H, d, J=6.2 Hz). 
       Example 42 
     Synthesis of N-methyl-N-(2-{[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)benzamide dihydrochloride 
       [1561]    The synthesis of the title compound was performed in the same manner as in Example 5 using appropriate starting materials. 
         [1562]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.15-2.41 (2H, m), 2.95 (3H, s), 3.01-3.51 (4H, m), 3.60 (3H, s), 3.70-4.24 (4H, m), 4.33-4.72 (2H, m), 6.61 (1H, d, J=9.5 Hz), 7.18 (1H, d, J=8.4 Hz), 7.25 (1H, s), 7.33-7.54 (6H, m), 7.82 (1H, d, J=9.5 Hz), 7.92-8.08 (2H, m), 8.67-8.82 (2H, m). 
       Example 43 
     Synthesis of 1-ethyl-6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1563]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1564]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.19 (3H, t, J=7.0 Hz), 2.18-2.41 (2H, m), 2.94-3.59 (6H, m), 3.96-4.18 (2H, m), 4.25 (2H, q, J=7.0 Hz), 4.35-4.63 (2H, m), 6.61 (1H, d, J=9.5 Hz), 7.18 (1H, dd, J=9.3, 2.8 Hz), 7.27 (1H, d, J=2.8 Hz), 7.52 (1H, d, J=9.3 Hz), 7.61-7.76 (1H, m), 7.85 (1H, d, J=9.5 Hz), 7.85-8.00 (2H, m), 8.09-8.20 (1H, m), 8.67 (1H, dd, J=5.3, 1.4 Hz), 8.69-8.80 (3H, m). 
       Example 44 
     Synthesis of 1-benzyl-6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1565]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1566]      1 H-NMR (DMSO-d 6 ) δ ppm: 1.80-2.00 (2H, m), 2.52-2.82 (6H, m), 3.63 (2H, s), 3.78-3.98 (2H, m), 5.54 (2H, s), 6.82 (1H, d, J=9.5 Hz), 6.84-6.99 (2H, m), 7.05-7.44 (10H, m), 7.67 (1H, d, J=9.5 Hz), 8.30-8.52 (4H, m). 
       Example 45 
     Synthesis of N-methyl-N-(2-{[3-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)benzamide dihydrochloride 
       [1567]    Benzoyl chloride (0.14 ml) was added to a dichloromethane solution (10 ml) of 6-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-isoquinolin-1-one trihydrochloride (382 mg), and triethylamine (0.56 ml) under ice cooling. The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extrcation using dichloromethane. The organic layer was dried with anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=10:1→4:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.28 ml) was added to an ethyl acetate solution (10 ml) of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (242 mg) as a white powder. 
         [1568]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.04-2.36 (2H, m), 2.78-2.92 (2H, m), 2.95 (3H, s), 3.00-3.46 (6H, m), 3.64-3.94 (2H, m), 3.94-4.21 (2H, m), 4.31-4.61 (2H, m), 6.77 (1H, s), 6.81 (1H, d, J=8.5 Hz), 7.29-7.59 (6H, m), 7.78 (1H, d, J=8.5 Hz), 7.91-8.18 (2H, m), 8.78 (2H, d, J=4.9 Hz). 
       Example 46 
     Synthesis of 2,3-dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochloride 
       [1569]    PS-Carbodiimide resin (1.3 g) and 1-hydroxy benzotriazole (HOBt) (230 mg) were added to acetonitrile and THF solution (4 ml+6 ml) of 1-methyl-6-{3-[(2-methylamino ethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one (304 mg) and 2,3-dihydrobenzofuran-7-carboxylic acid (164 mg). The mixture was stirred at room temperature overnight. After the reaction mixture was filtrated and condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=1:0→10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.35 ml) was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (324.2 mg) as a white powder. 
         [1570]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.10-2.44 (2H, m), 2.88-3.45 (6H, m), 2.91 (3H, s), 3.59 (3H, s), 3.70-4.25 (4H, m), 4.31-4.72 (4H, m), 6.58 (1H, d, J=9.5 Hz), 6.75-6.91 (1H, m), 6.91-7.12 (1H, m), 7.12-7.32 (3H, m), 7.43 (1H, d, J=9.0 Hz), 7.78 (1H, d, J=9.5 Hz), 7.98-8.30 (2H, m), 8.69-8.94 (2H, m). 
       Example 47 
     Synthesis of 3-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-7,8-dihydro-6H-5-thia-8-aza-benzocyclohepten-9-one trihydrochloride 
       [1571]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [1572]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.10-2.41 (2H, m), 3.00-3.60 (10H, m), 3.99-4.19 (2H, m), 4.43-4.84 (2H, m), 6.89-7.01 (2H, m), 7.48 (1H, d, J=8.6 Hz), 7.98 (1H, dd, J=8.0, 5.3 Hz), 8.04-8.21 (2H, m), 8.27 (1H, t, J=6.5 Hz), 8.46 (1H, d, J=8.0 Hz), 8.81 (1H, d, J=5.3 Hz), 8.81-8.98 (3H, m). 
       Example 48 
     Synthesis of 1-methyl-3-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1H-quinolin-2-one trihydrochloride 
       [1573]    The synthesis of the title compound was performed in the same manner as in Example 31 using appropriate starting materials. 
         [1574]      1 H-NMR (DMSO-d 6 ) δ ppm: 2.20-2.42 (2H, m), 3.10-3.33 (2H, m), 3.34-3.60 (4H, m), 3.67 (3H, s), 4.00-4.20 (2H, m), 4.55-4.82 (2H, m), 7.20-7.35 (2H, m), 7.40-7.53 (2H, m), 7.65 (1H, d, J=7.7 Hz), 7.93-8.08 (1H, m), 8.18-8.35 (2H, m), 8.53 (1H, d, J=8.1 Hz), 8.82 (1H, d, J=5.1 Hz), 8.90-9.05 (3H, m). 
       Example 49 
     Synthesis of 1-(6-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-quinolin-1-yl)ethanone trihydrochloride 
       [1575]    The synthesis of the title compound was performed in the same manner as in Example 32 using appropriate starting materials. 
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE U 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 798 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 799 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 478 
               
               
                   
               
               
                 800 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 801 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 802 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 474 
               
               
                   
               
               
                 803 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 405 
               
               
                   
               
               
                 804 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 472 
               
               
                   
               
               
                 805 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 806 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 469 
               
               
                   
               
               
                 807 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 456 
               
               
                   
               
               
                 808 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 809 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 483 
               
               
                   
               
               
                 810 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 811 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
               
               
                 812 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 488 
               
               
                   
               
               
                 813 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 516 
               
               
                   
               
               
                 814 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 516 
               
               
                   
               
               
                 815 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 816 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 477 
               
               
                   
               
               
                 817 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 818 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 819 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 820 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 821 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 822 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 503 
               
               
                   
               
               
                 823 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 824 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 461 
               
               
                   
               
               
                 825 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
               
               
                 826 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
               
               
                 827 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 828 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 502 
               
               
                   
               
               
                 829 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 488 
               
               
                   
               
               
                 830 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 831 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 832 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 459 
               
               
                   
               
               
                 833 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
               
               
                 834 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
               
               
                 835 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 836 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 837 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 838 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 839 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 474 
               
               
                   
               
               
                 840 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 841 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 469 
               
               
                   
               
               
                 842 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 443 
               
               
                   
               
               
                 843 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 485 
               
               
                   
               
               
                 844 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 499 
               
               
                   
               
               
                 845 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 846 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 458 
               
               
                   
               
               
                 847 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 484 
               
               
                   
               
               
                 848 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 849 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 485 
               
               
                   
               
               
                 850 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 469 
               
               
                   
               
               
                 851 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 852 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 853 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 456 
               
               
                   
               
               
                 854 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 461 
               
               
                   
               
               
                 855 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 856 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 857 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 858 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 444 
               
               
                   
               
               
                 859 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 860 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 473 
               
               
                   
               
               
                 861 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 862 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
               
                 863 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 487 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE V 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                   
                   
                   
                   
                   
                 MS 
               
               
                 No. 
                 R2 
                 R3 
                 R4 
                 R5 
                 R6 
                 (M + 1) 
               
               
                   
               
               
                 864 
                 —H 
                 —H 
                 —H 
                 —H 
                 —H 
                 428 
               
               
                 865 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 458 
               
               
                 866 
                 —H 
                 —N(CH 3 ) 2   
                 —H 
                 —H 
                 —H 
                 471 
               
               
                 867 
                 —H 
                 —H 
                 —N(CH 3 ) 2   
                 —H 
                 —H 
                 471 
               
               
                 868 
                 —H 
                 —H 
                 —CN 
                 —H 
                 —H 
                 453 
               
               
                 869 
                 —COCH 3   
                 —H 
                 —H 
                 —H 
                 —H 
                 470 
               
               
                 870 
                 —H 
                 —H 
                 —COCH 3   
                 —H 
                 —H 
                 470 
               
               
                 871 
                 —OC 6 H 5   
                 —H 
                 —H 
                 —H 
                 —H 
                 520 
               
               
                 872 
                 —H 
                 —H 
                 —OC 6 H 5   
                 —H 
                 —H 
                 520 
               
               
                 873 
                 —CN 
                 —H 
                 —H 
                 —H 
                 —H 
                 453 
               
               
                 874 
                 —H 
                 —H 
                 —C 6 H 5   
                 —H 
                 —H 
                 504 
               
               
                 875 
                 —H 
                 —H 
                 —SO 2 CH 3   
                 —H 
                 —H 
                 506 
               
               
                 876 
                 —H 
                 —H 
                 —N(C 2 H 5 ) 2   
                 —H 
                 —H 
                 499 
               
               
                 877 
                 —H 
                 —C 6 H 5   
                 —H 
                 —H 
                 —H 
                 504 
               
               
                   
               
               
                 878 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 511 
               
               
                   
               
               
                 879 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 493 
               
               
                   
               
               
                 880 
                 —H 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 494 
               
               
                   
               
               
                 881 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 —H 
                 509 
               
               
                   
               
               
                 882 
                 —H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 —H 
                 —H 
                 —H 
                 495 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE W 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R2 
                 R3 
                 R4 
                 R5 
                 R6 
                 MS(M + 1) 
               
               
                   
               
               
                 883 
                 —H 
                 —H 
                 —CH 3   
                 —H 
                 —H 
                 456 
               
               
                 884 
                 —H 
                 —H 
                 —F 
                 —H 
                 —H 
                 460 
               
               
                 885 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 —H 
                 472 
               
               
                 886 
                 —H 
                 —H 
                 —H 
                 —H 
                 —CH 3   
                 456 
               
               
                 887 
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 —H 
                 472 
               
               
                 888 
                 —H 
                 —H 
                 —H 
                 —H 
                 —OCH 3   
                 472 
               
               
                 889 
                 —H 
                 —H 
                 —OCH 3   
                 —OH 
                 —H 
                 488 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE X 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                   
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
                   
               
               
                   
                 890 
                 —CH 2 OC 6 H 5   
                 458 
               
               
                   
                 891 
                 —(CH 2 ) 2 C 6 H 5   
                 456 
               
               
                   
                 892 
                 —CH═CHC 6 H 5   
                 454 
               
               
                   
                 893 
                 —(CH 2 ) 2 OC 6 H 5   
                 472 
               
               
                   
                 894 
                 —(CH 2 ) 3 C 6 H 5   
                 470 
               
               
                   
                 895 
                 —(CH 2 ) 4 C 6 H 5   
                 484 
               
               
                   
                 896 
                 —CH 2 SC 6 H 5   
                 474 
               
               
                   
                 897 
                 —(CH 2 ) 2 COC 6 H 5   
                 484 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
           
               
                 TABLE Y 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example No. 
                 R1 
                 MS(M + 1) 
               
               
                   
               
               
                 898 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 457 
               
               
                   
               
               
                 899 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 476 
               
               
                   
               
               
                 900 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 488 
               
               
                   
               
               
                 901 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 429 
               
               
                   
               
               
                 902 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 429 
               
               
                   
               
               
                 903 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 429 
               
               
                   
               
               
                 904 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 418 
               
               
                   
               
               
                 905 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 906 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 418 
               
               
                   
               
               
                 907 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 908 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 909 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 448 
               
               
                   
               
               
                 910 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 434 
               
               
                   
               
               
                 911 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 484 
               
               
                   
               
               
                 912 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 484 
               
               
                   
               
               
                 913 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 472 
               
               
                   
               
               
                 914 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 497 
               
               
                   
               
               
                 915 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 916 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 498 
               
               
                   
               
               
                 917 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 918 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 919 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 920 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 921 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 475 
               
               
                   
               
               
                 922 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 467 
               
               
                   
               
               
                 923 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 467 
               
               
                   
               
               
                 924 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 469 
               
               
                   
               
               
                 925 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 502 
               
               
                   
               
               
                 926 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
               
               
                 927 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 481 
               
               
                   
               
               
                 928 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 495 
               
               
                   
               
               
                 929 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 481 
               
               
                   
               
               
                 930 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 500 
               
               
                   
               
               
                 931 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 932 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 455 
               
               
                   
               
               
                 933 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 527 
               
               
                   
               
               
                 934 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 527 
               
               
                   
               
               
                 935 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 527 
               
               
                   
               
               
                 936 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 539 
               
               
                   
               
               
                 937 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 523 
               
               
                   
               
               
                 938 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 511 
               
               
                   
               
               
                 939 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 495 
               
               
                   
               
               
                 940 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 457 
               
               
                   
               
               
                 941 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 431 
               
               
                   
               
               
                 942 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 444 
               
               
                   
               
               
                 943 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 480 
               
               
                   
               
               
                 944 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 945 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 436 
               
               
                   
               
               
                 946 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 450 
               
               
                   
               
               
                 947 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 948 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 446 
               
               
                   
               
               
                 949 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 950 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 444 
               
               
                   
               
               
                 951 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
               
               
                 952 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 482 
               
               
                   
               
               
                 953 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 510 
               
               
                   
               
               
                 954 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 433 
               
               
                   
               
               
                 955 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 435 
               
               
                   
               
               
                 956 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 495 
               
               
                   
               
               
                 957 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 447 
               
               
                   
               
               
                 958 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 495 
               
               
                   
               
               
                 959 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 489 
               
               
                   
               
               
                 960 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 517 
               
               
                   
               
               
                 961 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 501 
               
               
                   
               
               
                 962 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 963 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 513 
               
               
                   
               
               
                 964 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
               
               
                 965 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
               
               
                 966 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 505 
               
               
                   
               
               
                 967 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 486 
               
               
                   
               
               
                 968 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 490 
               
               
                   
               
               
                 969 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 419 
               
               
                   
               
               
                 970 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 500 
               
               
                   
               
               
                 971 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 508 
               
               
                   
               
               
                 972 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 508 
               
               
                   
               
               
                 973 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 433 
               
               
                   
               
               
                 974 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 468 
               
               
                   
               
               
                 975 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 484 
               
               
                   
               
               
                 976 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 514 
               
               
                   
               
               
                 977 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 509 
               
               
                   
               
               
                 978 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 482 
               
               
                   
               
               
                 979 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 498 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE Z 
               
               
                   
               
               
                 Example No. 
                 structure 
                 MS(M + 1) 
               
               
                   
               
             
             
               
                 981 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 628 
               
               
                   
               
               
                 982 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 446 
               
               
                   
               
               
                 983 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 502 
               
               
                   
               
               
                 984 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 474 
               
               
                   
               
               
                 985 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 530 
               
               
                   
               
               
                 986 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 544 
               
               
                   
               
             
          
         
       
     
       Pharmacological Test 1 
     (1) Production of Human Kv1.5-Expressing CHO-K1 Cell Lines 
       [1576]    CHO-K1 cell lines stably expressing human Kv1.5 channels were prepared in the following manner. 
         [1577]    Full-length human Kv1.5 cDNA was cloned from a human heart cDNA library (produced by Stratagene). The obtained human Kv1.5 sequence corresponds to the sequence described in FASEB J. 5, 331-337 (1991). 
         [1578]    The obtained human Kv1.5 cDNA was inserted into a plasmid encoding a CMV promoter and a G418 resistance marker to produce a Kv1.5 expression vector. The human Kv1.5 expression vector was transfected into CHO-K1 cells by the lipofectamine method. After culturing the cells in an F-12 medium (produced by Invitrogen Corp.) containing 10% FBS (produced by Invitrogen Corp.) for 3 or 4 days, the medium was replaced with a FBS-containing F-12 medium that included 1,000 μg/ml of G418 (produced by Invitrogen Corp.), and single colonies were isolated. The amount of Kv1.5 channel expression in the single colonies was quantified at the mRNA level by RT-PCR and then quantified at the protein level by western blotting. Finally, the expressed current was analyzed by patch clamp method. Cell lines expressing a current of 200 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamp method. 
       (2) Production of CHO Cell Line Expressing Human GIRK1/4 
       [1579]    CHO cell lines stably expressing human GIRK1/4 channels were prepared in the following manner. 
         [1580]    Full-length human GIRK1 cDNA was cloned from HuH cell- and HeLa cell-derived cDNA libraries. Full-length GIRK4 cDNA was amplified from a human heart cDNA library (produced by Clontech Laboratories, Inc.) by PCR using synthetic primers shown in Table 1, and cloned into the Eco-RI restriction enzyme site of pCR-Blunt (produced by Invitrogen Corporation) or into the HincII site of pUC118 (produced by Takara Bio, Inc.). 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Primer 
                 Sequence 
                   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 hGIRK1-S 
                 5′-ATGTCTGCACTCCGAAGGAAATTTG-3′ 
                 SEQ ID No. 1 
               
               
                   
               
               
                 hGIRK1-A 
                 5′-TTATGTGAAGCGATCAGAGTTC-3′ 
                 SEQ ID No. 2 
               
               
                   
               
               
                 hGIRK1-F2 
                 5′-GCAGGGTACCCCTTCGTATTATGTCTGCACTCC-3′ 
                 SEQ ID No. 3 
               
               
                   
               
               
                 hGIRK1-A3 
                 5′-GGTGTCTGCCGAGATTTGA-3′ 
                 SEQ ID No. 4 
               
               
                   
               
               
                 hGIRK1-A4 
                 5′-CCGAGTGTAGGCGATCACCC-3′ 
                 SEQ ID No. 5 
               
               
                   
               
               
                 hGIRK4-S 
                 5′-ATGGCTGGCGATTCTAGGAATGCC-3′ 
                 SEQ ID No. 6 
               
               
                   
               
               
                 hGIRK4-A 
                 5′-TCTCACCGAGCCCCTGGCCTCCC-3′ 
                 SEQ ID No. 7 
               
               
                   
               
               
                 hGIRK4-S2 
                 5′-AACCAGGACATGGAGATTGG-3′ 
                 SEQ ID No. 8 
               
               
                   
               
               
                 hGIRK4-A2 
                 5′-GAGAACAGGAAAGCGGACAC-3′ 
                 SEQ ID No. 9 
               
               
                   
               
             
          
         
       
     
         [1581]    The obtained human GIRK1 and GIRK4 cDNA sequences correspond to known sequences (NCBI database: GIRK1 (NM — 002239) and GIRK4 (NM — 000890) respectively). The obtained GIRK1 and GIRK4 cDNA sequences were cloned into the Eco-RI restriction enzyme site of pCR-Blunt (available from Invitrogen Corporation) or into the HincII site of pUC118 (available from Takara Bio, Inc.). A GIRK4 expression vector was constructed by insertion into the BamHI-XhoI site of pcDNA5/FRT. A GIRK1 expression vector was constructed by insertion into the KpnI-XhoI site of pcDNA3.1 (+) or pCAG_neo. FLP-IN-CHO cells (produced by Invitrogen Corporation) were transfected with human GIRK1 and GIRK4 expression vectors by using Lipofectamine 2000 (produced by Invitrogen Corporation) according to the protocol enclosed with the reagent or using an electronic induction method (“Nucleofector Kit-T”, produced by Amaxa). First, the cells transfected with the GIRK4 expression vector were cultured in a 10% serum-containing F12 medium (produced by Sigma) supplemented with 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. Then the cells expressing GIRK4 were transfected with the GIRK1 expression vector and were cultured in 10% serum-containing F12 medium supplemented with 350 μg/ml of G418 and 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. to select GIRK1/4 expressing cell lines. Cell populations whose growth was observed after about 2 weeks were isolated using cloning rings, and the obtained single colonies were proliferated. RNA was extracted from single colonies, and single-stranded cDNA was synthesized by a cDNA synthesis kit (produced by Invitrogen Corporation), and the amount of expression was quantified at the mRNA level by real-time PCR (Applied Biosystems, Ltd.). Finally, the expressed current was analyzed by patch clamp method described below. The cell lines expressing a current of 500 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamping method. 
       (3) Measurement of Ion Channel Current by Patch Clamp Method (Human Kv1.5-Expressing CHO-K1 Cell Line) 
       [1582]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolated table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human Kv1.5-expressing cells were cultured was placed in the perfusion chamber. 
         [1583]    Depolarizing stimulation pulses were applied and ionic current was recorded by using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, produced by HEKA) and a personal computer (manufactured by IBM Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, produced by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1584]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   40 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose 
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1585]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1586]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate 
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (4) Measurement of Ion Channel Current by Patch Clamp Method (Human GIRK1/4-Expressing CHO-K1 Cell Line) 
       [1587]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolation table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human GIRK1/4-expressing cells were cultured was placed in the perfusion chamber. 
         [1588]    Hyperpolarizing stimulation pulses were applied and ionic current was recorded using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, manufactured by HEKA) and a personal computer (manufactured by IBM Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, manufactured by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1589]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   4 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose 
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1590]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1591]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate  
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (5) Measurement of Human Kv1.5 Current 
       [1592]    While the membrane potential was holded at −80 mV, depolarizing pulses (−80 mV for 0.05 seconds→□□+40 mV for 0.2 seconds→□/□−40 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure Kv1.5 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and holding the membrane potential at −80 mV, depolarizing pulses were applied. The current obtained during the pulse application was recorded as a current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and holding the membrane potential at −80 mV, depolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration was recorded. 
         [1593]    The data was analyzed by using the step end current recorded during the +40 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the +40 mV depolarizing pulse stimulation. 
         [1594]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (6) Measurement of Human GIRK1/4 Current 
       [1595]    While the membrane potential was holded at −80 mV, hyperpolarizing pulses (−80 mV for 0.05 seconds→□□−120 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure GIRK1/4 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. The current obtained during the pulse application was recorded as the current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration were recorded. 
         [1596]    The data was analyzed by using the step end current recorded during the −120 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the −120 mV depolarizing pulse stimulation. 
         [1597]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (7) Calculation of Inhibitory Activity on Kv1.5 Channel Ionic Current and GIRK1/4 Channel Current 
       [1598]    The concentration for 50% inhibition of Kv1.5 channel current or GIRK1/4 channel current (IC 50  value) was calculated according to the following nonlinear regression equation: 
         [0000]      Relative current=1/(1+[Concentration of the compound]/IC 50 ) nH    
         [0000]    wherein nH is the Hill coefficient. 
         [1599]    Table 2 shows the test results. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Test Compound 
                 KV1.5 IC 50  (μM) 
               
               
                   
                   
               
             
             
               
                   
                 Compound of Example 14 
                 0.23 
               
               
                   
                 Compound of Example 18 
                 0.39 
               
               
                   
                 Compound of Example 24 
                 0.32 
               
               
                   
                 Compound of Example 26 
                 0.30 
               
               
                   
                 Compound of Example 34 
                 0.33 
               
               
                   
                 Compound of Example 38 
                 0.38 
               
               
                   
                 Compound of Example 40 
                 0.86 
               
               
                   
                 Compound of Example 42 
                 0.77 
               
               
                   
                 Compound of Example 46 
                 0.42 
               
               
                   
                 Compound of Example 62 
                 0.12 
               
               
                   
                   
               
             
          
         
       
     
       3. Third Invention 
     Reference Example 1 
     Synthesis of ethyl N-(5-methoxy-2-nitrophenyl)-N-methyl malonamate 
       [1600]    Sodium hydride (60% in oil, 96 mg) was suspended in 10 ml of dimethylformamide (DMF). N-Methyl-5-methoxy-2-nitroaniline (364 mg) was added thereto at 0° C., and stirring was conducted at room temperature for 30 minutes. Ethyl malonyl chloride (0.38 ml) was added at 0° C. to the stirred mixture, and the reaction mixture was stirred at room temperature overnight. Water was added thereto, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:2). The purified product was concentrated under reduced pressure to give the title compound (554 mg) as a yellow oil. 
         [1601]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1602]    1.24 (3H, t, J=7.1 Hz), 3.15-3.17 (2H, m), 3.25 (3H, s), 3.92 (3H, s), 4.13 (2H, q, J=7.1 Hz), 6.93 (1H, d, J=2.8 Hz), 7.02 (1H, dd, J=2.8 and 9.2 Hz), 8.15 (1H, d, J=9.2 Hz). 
       Reference Example 2 
     Synthesis of ethyl N-(2-amino-5-methoxyphenyl)-N-methyl malonamate 
       [1603]    Palladium on carbon (10%, 0.5 g) was added to an ethanol solution (150 ml) of ethyl N-(5-methoxy-2-nitrophenyl)-N-methyl malonamate (3.0 g), and catalytic reduction was conducted at room temperature and normal pressure. The reaction mixture was filtered through Celite to remove the catalyst. The filtrate was concentrated under reduced pressure to give the title compound (2.68 g) as a yellow oil. 
         [1604]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1605]    1.22 (3H, t, J=7.1 Hz), 3.19-3.27 (5H, m), 3.52-3.68 (2H, br), 3.74 (3H, s), 4.11 (2H, q, J=7.1 Hz), 6.62 (1H, d, J=2.7 Hz), 6.73 (1H, d, J=8.7 Hz), 6.79 (1H, dd, J=2.7 and 8.7 Hz). 
       Reference Example 3 
     Synthesis of 8-methoxy-1-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1606]    Sodium ethoxide (204 mg) was added to an ethanol solution (15 ml) of ethyl N-(2-amino-5-methoxyphenyl)-N-methyl malonamate (266 mg), and stirred at 65° C. for 2.5 hours. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=1:0→10:1). The purified product was concentrated to dryness under reduced pressure to give the title compound (176.3 mg) as a white powder. 
         [1607]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1608]    3.36 (2H, s), 3.43 (3H, s), 3.84 (3H, s), 6.79-6.83 (1H, m), 7.06-7.09 (1H, m), 8.72 (1H, br-s). 
       Reference Example 4 
     Synthesis of 1-ethyl-7-methoxy-5-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1609]    Sodium hydride (60% in oil, 44 mg) was suspended in dimethylformamide (DMF) (8 ml), and cooled in an ice water bath to 0° C. 8-Methoxy-1-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (220 mg) was added to the suspension at the same temperature, and stirred at 0° C. for 1 hour. Ethyl iodide (187 mg) was added to the mixture and stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1→1:1). The purified product was concentrated to dryness under reduced pressure to give the title compound (190.2 mg) as a yellow solid. 
         [1610]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1611]    1.11 (3H, t, J=7.1 Hz), 3.31-3.32 (2H, m), 3.40 (3H, s), 3.59-3.68 (1H, m), 3.85 (3H, s), 4.18-4.30 (1H, m), 6.78 (1H, d, J=2.8 Hz), 6.84 (1H, dd, J=9.0 and 2.8 Hz), 7.26 (1H, d, J=9.0 Hz). 
       Reference Example 5 
     Synthesis of 1-ethyl-7-methoxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1612]    Sodium hydride (60% in oil, 76 mg) was suspended in DMF (8 ml). 1-Ethyl-7-methoxy-5-methyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (190 mg) was added thereto at 0° C., and stirring was conducted at the same temperature for 1 hour. Methyl iodide (0.19 ml) was added to the mixture, and stirred at room temperature for 3 days. Water was added to the reaction mixture, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The purified product was concentrated to dryness under reduced pressure to give the title compound (169 mg) as a yellow powder. 
         [1613]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1614]    0.86 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.40 (3H, s), 3.65-3.76 (1H, m), 3.85 (3H, s), 4.12-4.24 (1H, m), 6.73 (1H, d, J=2.8 Hz), 6.83 (1H, dd, J=9.0 and 2.8 Hz), 7.22 (1H, d, J=9.0 Hz). 
       Reference Example 6 
     Synthesis of 1-ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1615]    A 1.0 M boron tribromide/dichloromethane solution (1.22 ml) was added to a dichloromethane solution (3 ml) of 1-ethyl-7-methoxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (169 mg) at 0° C., and stirred at room temperature overnight. Water and methanol were added to the reaction mixture and extraction with the mixture solvent (dichloromethane:methanol=10:1) was performed. The organic layer was dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to give the title compound (156.4 mg) as a white powder. 
         [1616]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1617]    0.90 (3H, s), 1.16 (3H, t, J=7.0 Hz), 1.55 (3H, s), 3.41 (3H, s), 3.66-3.78 (1H, m), 4.12-4.23 (1H, m), 6.79 (1H, d, J=2.7 Hz), 6.84 (1H, dd, J=8.8 and 2.7 Hz), 6.88 (1H, d, J=2.7 Hz), 7.18 (1H, d, J=8.8 Hz). 
       Reference Example 7 
     Synthesis of 7-(3-chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1618]    1-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.85 g) and potassium carbonate (1.2 g) were added to 50% water-containing acetonitrile (40 ml), and dissolved by heating to 70° C. 1-Bromo-3-chloropropane (2.1 ml) was added thereto, and heating was conducted under reflux for 6 hours. The reaction mixture was cooled to room temperature. Water was added, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1→1:1). The purified product was concentrated to dryness under reduced pressure to give the title compound (2.18 g) as a colorless oil. 
         [1619]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1620]    0.86 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.21-2.38 (2H, m), 3.40 (3H, s), 3.63-3.89 (4H, m), 4.10-4.26 (2H, m), 6.74 (1H, d, J=2.8 Hz), 6.83 (1H, dd, J=2.8 and 9.0 Hz), 7.21 (1H, d, J=9.0 Hz). 
       Reference Example 8 
     Synthesis of 1-ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1621]    7-(3-Chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione (2.18 g) and sodium iodide (4.8 g) were added to acetone (50 ml), and heated under reflux for 8.5 hours. The reaction mixture was cooled to room temperature, water was added, and extraction with ethyl acetate was performed. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1). The purified product was concentrated under reduced pressure to give the title compound (2.76 g) as a colorless oil. 
         [1622]      1 H-NMR (CDCl 3 ) δ ppm: 
         [1623]    0.87 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.26-2.34 (2H, m), 3.39 (2H, t, J=6.6 Hz), 3.65-3.76 (1H, m), 3.41 (3H, s), 4.07 (2H, t, J=5.8 Hz), 4.12-4.24 (1H, m), 6.74 (1H, d, J=2.8 Hz), 6.83 (1H, dd, J=9.0 and 2.8 Hz), 7.22 (1H, d, J=9.0 Hz). 
       Reference Example 9 
     Synthesis of 3-iodoquinolin-4-ol 
       [1624]    Potassium carbonate (5.2 g) was added to a DMF solution (50 ml) of 4-hydroxy quinoline (5.0 g) and the mixture was stirred. Iodine (9.6 g) was added to the mixture, followed by stirring at room temperature for 3 hours. A saturated sodium hydrogencarbonate aqueous solution (73 ml) of 25% sodium sulfite, and water (50 ml) were added to the reaction mixture. The mixture was stirred and the precipitated insoluble matter was separated. The filtrate was washed with water and dried to give the title compound (9.0 g) as a white powder. 
       mp: 288 to 294° C. (dec.) 
     Reference Example 10 
     Synthesis of 3-bromoquinolin-4-ol 
       [1625]    N-Bromosuccinimide (1.3 g) was added to a DMF solution (15 ml) of 4-hydroxy quinoline (1.0 g) and the mixture was stirred at room temperature for 15 hours. A sodium hydrogencarbonate aqueous solution of 25% sodium sulfite was added to the mixture. The mixture was stirred and the precipitated insoluble matter was separated. The filtrate was dissolved in a mixture of ethyl acetate and methanol, and an insoluble matter was removed by filtration. The filtrate was condensed under reduced pressure, and the residue was washed with ethyl acetate and dried to give the title compound (1.1 g) as a white powder. 
       mp: 286 to 287° C. 
     Reference Example 11 
     Synthesis of 3-bromo-1H-quinolin-2-one 
       [1626]    Hydrogen peroxide solution (5.9 ml) was added to a THF solution (16 ml) of methyltrioxorhenium (VII) (24 mg). The mixture was stirred for 10 minutes at room temperature. 3-Bromoquinoline (4.0 g) was added thereto, and the mixture was stirred at room temperature for four days. Ethyl acetate (20 ml) was added to the reaction mixture. 20% Sodium sulfite aqueous solution (30 ml) was added slowly to the mixture under ice cooling. The mixture was stirred at room temperature. The organic layer was condensed to a half volume under reduced pressure. Ethyl acetate (20 ml) and 15% potassium carbonate aqueous solution (19 ml) were added thereto, and the organic layer was extracted. 15% Potassium carbonate aqueous solution (19 ml) of p-toluenesulfonyl chloride (4 g) were added thereto. The mixture was stirred for 10 minutes at room temperature. The generated insoluble matter was separated, washed with ethyl acetate, water, and then with ether, and dried to give the title compound (3.2 g) as a white powder. 
       mp: 263 to 265° C. 
     Reference Example 12 
     Synthesis of 1-(pyridin-3-yl)-2,3-dihydrobenzoimidazol-2-one 
       [1627]    N,N′-Carbonyldiimidazole (0.57 g) was added to a DMF solution (5 ml) of N-pyridine-3-ylbenzene-1,2-diamine (0.5 g). The mixture was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture and the precipitated insoluble matter was separated, washed with water, and dried to give the title compound (0.5 g) as a pale whitish purple powder. 
       mp: 232 to 233° C. (dec.). 
     Reference Example 13 
     Synthesis of 5-(2,2-dihydroxyethyl)-2-methyl-5H-furo[3,2-c]pyridin-4-one 
       [1628]    Sodium hydride (60% in oil, 0.32 g) was suspended in DMF (10 ml), and was cooled to 0° C. in an ice water bath. 2-Methyl-5H-furo[3,2-c]pyridin-4-one (0.57 g) was added thereto at the same temperature, and the mixture was stirred at 0° C. for an hour. Bromoacetaldehyde dimethylacetal (2.3 ml) was added thereto, and the mixture was stirred at 80° C. for 5 hours. Water was added to the reaction liquid, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. A 3N-hydrochrolic acid (2 ml) was added to an acetone solution (10 ml) of the residue, and the liquid was stirred at 70° C. for 10 hours. Water was added to the reaction liquid and stirred at room temperature. The precipitated insoluble matter was separated, washed with water, and dried to give the title compound (0.56 g) as a white solid. 
         [1629]      1 H-NMR (DMSO-D 6 ) ppm: 2.36 (s, 3H), 3.86 (d, J=5.4 Hz, 2H), 4.94-4.98 (m, 1H), 6.04 (d, J=6.4 Hz, 2H), 6.52 (s, 1H), 6.59 (d, J=7.4 Hz, 1H), 7.41 (d, J=7.4H, 1H). 
       Reference Example 14 
     Synthesis of 5-(1H-benzoimidazol-2-ylmethyl)-2-methyl-5H-furo[3,2-c]pyridin-4-one 
       [1630]    5-(2,2-Dihydroxyethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (2.1 g) and o-phenylenediamine (1.1 g) were suspended in ethanol (20 ml). Sodium hydrogensulfite (5.2 g) was added, and the mixture was heated and stirred overnight under reflux. The reaction mixture was cooled to room temperature. Water was added thereto and the precipitated insoluble matter was separated, washed with water, and dried to give the title compound (2.25 g). 
         [1631]      1 H NMR (CDCl 3 ), δ ppm: 2.36 (3H, s), 5.44 (2H, s), 6.55 (1H, s), 6.73 (1H, d, J=7.4 Hz), 7.05-7.15 (2H, m), 7.43 (1H, d, J=7.0 Hz), 7.50 (1H, d, J=8.3 Hz), 7.70 (1H, d, J=7.4 Hz). 
       Reference Example 15 
     Synthesis of 3-(pyridin-3-yl)-1H-quinolin-4-one 
       [1632]    2N Hydrochloric acid (10 ml) was added to a DMF solution (5 ml) of 4-chloro-(3-pyridin-3-yl)quinoline (0.51 g), and the mixture was stirred at 80° C. for 1 hour. After the reaction mixture was cooled to room temperature, 2N sodium hydroxide aqueous solution (10 ml) was added dropwise under ice cooling. The mixture was stirred. The precipitated insoluble matter was separated, washed with water and ether, and dried to give the title compound (0.35 g) as a pale whitish purple powder. 
       mp: 240 to 242° C. (dec.) 
     Reference Example 16 
     Synthesis of 5-[{1-(3-chloropropyl)-1H-benzoimidazol-2-yl}methyl]-2-methyl-5H-furo[3,2-c]pyridin-4-one 
       [1633]    5-(1H-Benzimidazol-2-ylmethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.75 g), 1-bromo-3-chloropropane (1.3 ml), and potassium carbonate (0.95 g) were added to 50% hydrous acetonitrile (16 ml). The mixture was heated overnight under reflux. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1). The purified product was condensed to dryness under reduced pressure to give the title compound (0.18 g) as a colorless oily matter. 
         [1634]      1 H NMR (CDCl 3 ), δ ppm: 2.02-2.09 (2H, m), 2.41 (3H, s), 3.54 (2H, t, J=6.1 Hz), 4.55-4.61 (2H, m), 5.56 (2H, s), 6.51-6.53 (2H, m), 7.24-7.32 (2H, m), 7.40-7.46 (1H, m), 7.54 (1H, d, J=5.9 Hz), 7.73-7.79 (1H, m). 
       Reference Example 17 
     Synthesis of 5-(3-chloropropyl)-2-methyl-5H-furo[3,2-c]pyridin-4-one 
       [1635]    Methane sulfonyl chloride (0.24 ml) was added to a dichloromethane solution (10 ml) of 5-(3-hydroxypropyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.28 g) and triethylamine (0.45 ml). The mixture was stirred at room temperature for two days. The reaction liquid was condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4→1:1). The purified product was condensed to dryness under reduced pressure to give the title compound (0.16 g) as a white amorphous solid. 
         [1636]      1 H NMR (CDCl 3 ), δ ppm: 2.25-2.41 (2H, m), 2.41 (3H, s), 3.56 (2H, t, J=6.1 Hz), 4.18 (2H, t, 6.6 Hz), 6.48 (1H, d, J=7.4 Hz), 6.55 (1H, s), 7.17 (1H, d, J=7.4 Hz). 
       Reference Example 18 
     Synthesis of 7-(2-chloroethoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1637]    1-Ethyl-7-hydroxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.2 g) and potassium carbonate (0.95 g) were added to 50% hydrous acetonitrile (24 ml). The mixture was heated to 70° C. to be dissolved. 1-Bromo-2-chloroethane (1.9 ml) was added, and the mixture was heated under reflux for 7 hours. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was dried by sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:1). The purified product was condensed to dryness under reduced pressure to give the title compound (1.4 g) as a colorless oily matter. 
         [1638]      1 H NMR (CDCl 3 ), δ ppm: 0.86 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 3.40 (3H, s), 3.64-3.77 (1H, m), 3.85 (2H, t, J=5.7 Hz), 4.03-4.15 (1H, m), 4.26 (2H, t, J=5.7 Hz), 6.77 (1H, d, J=2.8 Hz), 6.83 (1H, dd, J=9.0, 2.8 Hz), 7.23 (1H, d, J=9.0 Hz). 
       Reference Example 19 
     Synthesis of 7-[3-(3-aminopyridin-4-ylamino)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1639]    10% Palladium on carbon (0.7 g) was added to a methanol solution (30 ml) of 1-ethyl-3,3,5-trimethyl-7-[3-(3-nitropyridin-4-ylamino)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (1.8 g). The mixture was subjected to catalytic reduction at room temperature under normal pressure. The reaction mixture was subjected to celite filtration to remove the catalyst. The filtrate was condensed under reduced pressure to give the title compound (1.4 g) as an orange amorphous solid. 
         [1640]      1 H NMR (CDCl 3 ), δ ppm: 0.86 (3H, s), 1.14 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.12-2.24 (2H, m), 3.40 (3H, m), 3.40-3.52 (2H, m), 3.63-3.74 (1H, m), 4.03-4.14 (3H, m), 6.51 (1H, d, J=5.4 Hz), 6.75-6.76 (1H, m), 6.84 (1H, dd, J=9.0, 2.8 Hz), 7.22 (1H, d, J=9.0 Hz), 7.93 (1H, s), 7.98 (1H, d, J=5.4 Hz). 
       Example 1 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-phenylpiperidin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [1641]    Potassium carbonate (0.54 g), sodium iodide (0.21 g), and 2-phenyl piperidine (0.23 g) were added to a DMF solution (15 ml) of 7-(3-chloropropoxy)-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.44 g). The mixture was stirred at 70° C. for 5 hours. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was washed with water and then with saturated saline, and dried with anhydrous magnesium sulfate. After condensation under reduced pressure, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:1). The purified product was condensed under reduced pressure. A 4N-Hydrogen chloride ethyl acetate solution (0.2 ml) was added to an ethyl acetate solution (10 ml) of the residue, which was stirred at room temperature. The liquid was condensed to dryness under reduced pressure to give the title compound (0.18 g) as a white amorphous solid. 
         [1642]      1 H NMR (CDCl 3 ), δ ppm: 0.82 (3H, s), 1.12 (3H, t, J=7.0 Hz), 1.51 (3H, s), 1.89-3.22 (11H, m), 3.36 (3H, s), 3.62-3.97 (5H, m), 4.09-4.18 (1H, m), 6.53-6.54 (1H, m), 6.62-6.67 (1H, m), 7.16 (1H, d, J=9.0 Hz), 7.36-7.47 (3H, m), 7.61-7.90 (2H, m), 12.40 (1H, brs). 
       Example 2 
     Synthesis of 7-[3-((R)-2,4-dibenzylpiperazin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1643]    The synthesis of the title compound was performed in the same manner as in Example 1 using appropriate starting materials. 
         [1644]      1 H NMR (DMSO-d 6 ), δ ppm: 0.75 (3H, s), 1.01 (3H, t, J=6.8 Hz), 1.33 (3H, s), 2.15-2.40 (2H, m), 2.83-3.90 (13H, m), 3.97-4.61 (7H, m), 6.96-7.01 (2H, m), 7.28-7.44 (9H, m), 7.59 (2H, br). 
       Example 3 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{3-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-ylmethyl)benzimidazol-1-yl]propoxy}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1645]    5-(1H-Benzimidazol-2-ylmethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.28 g) and potassium carbonate (0.9 g) were added to a DMF solution (2 ml) of 1-ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione (0.43 g). The mixture was stirred at 60° C. overnight. After the reaction liquid was condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→4:1). The purified product was condensed to dryness under reduced pressure to give the title compound (0.43 g) as a white amorphous solid. 
         [1646]      1 H NMR (CDCl 3 ), δ ppm: 0.85 (3H, s), 1.15 (3H, t, J=7.1 Hz), 1.53 (3H, s), 2.12-2.23 (2H, m), 2.40 (3H, s), 3.38 (3H, s), 3.61-3.72 (1H, m), 3.95 (2H, t, J=5.7 Hz), 4.05-4.15 (1H, m), 4.65 (2H, t, J=6.5 Hz), 5.53 (2H, s), 6.49-6.55 (2H, m), 6.70-6.71 (1H, m), 6.74-6.80 (1H, m), 7.19 (1H, d, J=9.0 Hz), 7.24-7.27 (2H, m), 7.33-7.38 (1H, m), 7.54 (1H, d, J=7.5 Hz), 7.75-7.79 (1H, m). 
       Example 4 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[(2-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-ylmethyl)benzimidazol-1-yl]ethoxy]-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione 
       [1647]    Potassium carbonate (0.58 g), sodium iodide (0.21 g), and 5-(1H-benzimidazol-2-ylmethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.39 g) were added to a DMF solution (30 ml) of 7-(2-chloroethoxy)-1-ethyl-3,3,5-trimethyl-1,5-d′ hydrobenzo[b][1,4]diazepine-2,4-dione (0.47 g). The mixture was stirred at 65° C. overnight. The mixture was further stirred at 100° C. overnight. After the reaction mixture was condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=95:5→85:15). The purified product was condensed to dryness under reduced pressure to give the title compound (0.44 g) as a white amorphous solid. 
         [1648]      1 H NMR (CDCl 3 ), δ ppm: 0.77 (3H, s), 1.09 (3H, t, J=7.1 Hz), 1.49 (3H, s), 2.40 (3H, s), 3.26 (3H, s), 3.61-3.74 (1H, m), 4.05-4.18 (1H, m), 4.24 (2H, t, J=5.0 Hz), 4.93 (2H, t, J=5.0 Hz), 5.55-5.66 (2H, m), 6.44-6.45 (1H, m), 6.51-6.54 (2H, m), 6.57-6.64 (1H, m), 7.00 (1H, d, J=9.0 Hz), 7.25-7.36 (2H, m), 7.58-7.62 (1H, m), 7.63 (1H, d, 7.6 Hz), 7.77-7.80 (1H, m). 
       Example 5 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-phenyl-benzoimidazol-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [1649]    2-Phenyl-1H-benzimidazole (0.2 g) and potassium carbonate (0.29 g) were added to a DMF solution (5 ml) of 1-ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione (0.49 g). The mixture was stirred at 60° C. for 7 hours. The reaction mixture was poured to ice water (50 ml), and the generated insoluble matter was separated. The insoluble matter was dissolved in ethyl acetate. The liquid was dried over sodium sulfate and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:3). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride ethanol solution (1.0 ml) was added to an isopropyl alcohol solution of the residue. The mixture was condensed under reduced pressure. Ether was added to the residue. The generated insoluble matter was separated by filtration and dried to give the title compound (0.32 g) as a white powder. 
       mp: 132 to 134° C. 
     Example 6 
     Synthesis of 7-[3-(4-chloro-2-oxo-3-phenyl-2H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1650]    4-Chloro-3-phenyl-1H-quinoline-2-one (0.3 g) was suspended in DMF (6 ml). Sodium hydride (60% in oil) (51 mg) was added, and the mixture was stirred for 15 minutes at room temperature. 1-Ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione (0.55 g) was added thereto and the mixture was stirred at room temperature for 7 days. The reaction mixture was poured to ice water (50 ml), and the generated insoluble matter was separated. The insoluble matter was dissolved in ethyl acetate. The liquid was dried over sodium sulfate and condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→1:3). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether, thereby obtaining the title compound (0.28 g) as a white powder. 
       mp: 122 to 128° C. 
     Example 7 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-{3-[2-(2-methyl-4-oxo-4H-furo[3,2-c]pyridin-5-ylmethyl)imidazo[4,5-c]pyridin-1-yl]propoxy}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione dihydrochloride 
       [1651]    A DMF solution (4 ml) of 5-(2,2-dihydroxyethyl)-2-methyl-5H-furo[3,2-c]pyridine-4-one (0.20 g), 7-[3-(3-aminopyridin-4-ylamino)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.37 g), and sodium hydrogensulfite (0.47 g) were heated at 180° C. for 10 minutes (microwave reactor). After the reaction liquid was condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate:methanol=95:5→60:40). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution was added to an ethyl acetate solution of the residue, which was stirred at room temperature. The generated insoluble matter was separated by filtration, and dried to give the title compound (0.47 g) as a white amorphous solid. 
         [1652]      1 H NMR (DMSO-d 6 ), δ ppm: 0.70 (3H, s), 0.95 (3H, t, J=7.1 Hz), 1.30 (3H, s), 2.31-2.41 (2H, m), 2.40 (3H, s), 3.29 (3H, s), 3.60-3.70 (1H, m), 3.98-4.09 (1H, m), 4.16 (2H, t, J=6.0 Hz), 4.79 (2H, t, J=6.6 Hz), 5.67 (2H, s), 6.54 (1H, s), 6.80-6.85 (3H, m), 7.33 (1H, d, J=6.5 Hz), 7.76 (1H, d, J=7.5 Hz), 8.33 (1H, d, J=6.5 Hz), 8.60 (1H, d, J=6.5 Hz), 9.36 (1H, s). 
       Example 8 
     Synthesis of 7-[3-(3-bromo-2-oxo-2H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1653]    Under ice cooling, sodium hydride (60% in oil, 0.2 g) was added to a DMF solution (10 ml) of 3-bromo-1H-quinoline-2-one (1.0 g). The mixture was stirred at the same temperature for 15 minutes. Lithium bromide (0.76 g) was added to the mixture, and the liquid was stirred at the same temperature for another 15 minutes, and then at room temperature for an hour. The reaction mixture was cooled to 0° C., and 1-ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione (2.1 g) was added thereto. The mixture was stirred at room temperature for 2 hours, and at 50° C. for 8 hours. The reaction mixture was poured to ice water, and the generated insoluble matter was separated. The insoluble matter was dissolved in a mixed solvent of ethyl acetate and dichloromethane. The liquid was dried with sodium sulfate and condensed under reduced pressure. Ethyl acetate was added to the residue. The generated insoluble matter was separated and dried to give the title compound (1.2 g) as a white powder. 
       mp: 168 to 169° C. 
     Example 9 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-2H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1654]    The synthesis of the title compound was performed in the same manner as in Example 8 using appropriate starting materials. 
         [0000]    White powder 
       mp: 134 to 135° C. 
     Example 10 
     Synthesis of 1-ethyl-7-[3-(3-iodo-4-oxo-4H-quinolin-1-yl)propoxy]-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1655]    The synthesis of the title compound was performed in the same manner as in Example 8 using appropriate starting materials. 
         [0000]    White powder 
       mp: 97 to 106° C. 
     Example 11 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(4-oxo-3-(pyridin-3-yl)-4H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1656]    The synthesis of the title compound was performed in the same manner as in Example 8 using appropriate starting materials. 
         [0000]    White powder 
       mp: 199 to 201° C. 
     Example 12 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(4-oxo-4H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1657]    The synthesis of the title compound was performed in the same manner as in Example 8 using appropriate starting materials. 
         [0000]    White powder 
       mp: 174 to 177° C. 
     Example 13 
     Synthesis of 7-[3-(3-bromo-4-oxo-4H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1658]    The synthesis of the title compound was performed in the same manner as in Example 8 using appropriate starting materials. 
         [0000]    White powder 
       mp: 180 to 183° C. 
     Example 14 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-3-phenyl-2,3-dihydrobenzimidazol-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1659]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [1660]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.14 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.27-2.41 (2H, m), 3.36 (3H, s), 3.6-3.78 (1H, m), 4.09 (2H, t, J=5.9 Hz), 4.11-4.26 (1H, m), 4.20 (2H, t, J=6.6 Hz), 6.68 (1H, d, J=2.8 Hz), 6.80 (1H, dd, J=2.8, 9.0 Hz), 6.99-7.14 (4H, m), 7.19 (1H, d, J=9.0 Hz), 7.33-7.47 (1H, m), 7.47-7.58 (4H, m). 
       Example 15 
     Synthesis of 1-ethyl-7-[3-(3-hydroxy-2-oxo-3-phenyl-2,3-dihydroindol-1-yl)prop oxy]-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1661]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [0000]    White powder 
       mp: 153 to 156° C. 
     Example 16 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-3-(pyridin-3-yl)-2,3-dihydrobenzimidazol-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione hydrochloride 
       [1662]    1-(Pyridin-3-yl)-1,3-dihydrobenzimidazole-2-one (0.2 g) was suspended in DMF (6 ml). Sodium hydride (55% in oil, 48 mg) was added under ice cooling, and the mixture was stirred at room temperature for 30 minutes. 1-Ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4 ]diazepine-2,4-dione (0.45 g) was added to the mixture. The mixture was stirred at room temperature for 3 hours. The reaction mixture was poured to ice water (100 ml), followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The purified product was condensed under reduced pressure. A 0.5N-hydrogen chloride ethanol solution (1.9 ml) was added to an isopropyl alcohol solution of the residue. The mixture was condensed under reduced pressure. Ether was added to the residue. The generated insoluble matter was separated by filtration and dried to give the title compound (0.38 g) as a white powder. 
         [0000]    White powder 
       mp: 119 to 125° C. 
     Example 17 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2r-oxospiro[[1,3]dioxolane-2,3′-ind oline]-1′-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1663]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [0000]    White powder 
       mp: 143 to 147° C. 
     Example 18 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-phenylindol-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1664]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [0000]    White powder 
       mp: 140 to 142° C. 
     Example 19 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-3-phenyl-2H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1665]    7-[3-(3-Bromo-2-oxo-2H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.5 g), phenylboronic acid (0.12 g), tetrakis(triphenyl phosphine) palladium (0) (0.11 g), and potassium carbonate (0.39 g) were added to dioxane (5 ml). The mixture was heated under reflux for 2 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was dried over sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1→3:1). The purified product was condensed to dryness under reduced pressure, thereby obtaining the title compound (0.34 g) as a white amorphous solid. 
         [1666]      1 H NMR (CDCl 3 ), δ ppm: 0.84 (3H, s), 1.14 (3H, t, J=7.1 Hz), 1.52 (3H, s), 2.27-2.42 (2H, m), 3.37 (3H, s), 3.62-3.80 (1H, m), 4.05-4.28 (3H, m), 4.62 (2H, t, J=7.2 Hz), 6.72 (1H, d, J=2.7 Hz), 6.83 (1H, dd, J=2.7, 9.0 Hz), 7.19 (1H, d, J=9.0 Hz), 7.20-7.30 (1H, m), 7.32-7.58 (5H, m), 7.60-7.67 (1H, m), 7.67-7.74 (2H, m), 7.84 (1H, s). 
       Example 20 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(4-oxo-3-phenyl-4H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1667]    The synthesis of the title compound was performed in the same manner as in Example 19 using appropriate starting materials. 
         [0000]    White powder 
       mp: 150 to 152° C. 
     Example 21 
     Synthesis of 1-ethyl-7-{3-[3-(6-methoxypyridin-3-yl)-4-oxo-4H-quinolin-1-yl]propoxy}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1668]    The synthesis of the title compound was performed in the same manner as in Example 19 using appropriate starting materials. 
         [0000]    White powder 
       mp: 159 to 161° C. 
     Example 22 
     Synthesis of 1-ethyl-7-{3-[3-(6-methoxypyridin-3-yl)-4-oxo-4H-quinoline-1-yl]propoxy}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione mesylate 
       [1669]    Methanesulfonic acid (0.024 ml) was added to an ethyl acetate/isopropyl alcohol solution (1:1, 8 ml) of 1-ethyl-7-{3-[3-(6-methoxypyridin-3-yl)-4-oxo-4H-quinoline-1-yl]propoxy}-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.2 g) at 0° C., which was stirred at the same temperature for 2 hours. The precipitated insoluble matter was separated, washed with isopropyl alcohol, and dried to give the title compound (0.19 g) as a white powder. 
         [0000]    White powder 
       mp: 188 to 189° C. 
     Example 23 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-3-phenyl-3,4-dihydro-2H-quinolin-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1670]    10% Palladium on carbon (20 mg) was added to an ethanol/ethyl acetate solution (1:1, 4 ml) of 7-[3-(4-chloro-2-oxo-3-phenyl-2H-quinoline-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.19 g). The mixture was subjected to catalytic reduction at 50° C. under normal pressure for 6 hours. The reaction mixture was subjected to celite filtration to remove the catalyst. The filtrate was condensed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether/hexane, thereby obtaining the title compound (0.1 g) as a white powder. 
       mp: 100 to 105° C. 
     Example 24 
     Synthesis of 7-[3-(2,3-dioxo-2,3-dihydroindol-1-yl)propoxy]-1-ethyl-3,3,5-trim ethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1671]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [0000]    Orange powder 
       mp: 162 to 163° C. 
     Example 25 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-[3-(2-oxo-2,3-dihydroindol-1-yl)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione 
       [1672]    7-[3-(2,3-Dioxo-2,3-dihydroindol-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.3 g) was suspended in hydrazine hydrate (3 ml), and the liquid was stirred for two hours while heated under reflux. The reaction mixture was cooled to room temperature. Water was added thereto, followed by extraction by ethyl acetate. The organic layer was dried by anhydrous sodium sulfate, and condensed under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=85:15). The purified product was condensed under reduced pressure, and the residue was recrystallized from ether/hexane, thereby obtaining the title compound (0.18 g) as a pale brownish white powder. 
       mp: 146 to 149° C. 
     Example 26 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(3-((3-(1-oxoisoquinolin-2(2H)-yl)propyl)(pyridin-4-ylmethyl)amino)propoxy)-1H-benzo[b][1,4]diazepine-2, 4 (3H, 5H)-dione 
       [1673]    The synthesis of the title compound was performed in the same manner as in Example 6 using appropriate starting materials. 
         [1674]      1 H-NMR (CDCl 3 ) δ ppm: 0.84 (s, 3H), 1.14 (t, J=7.1 Hz, 3H), 1.51 (s, 3H), 1.90-2.00 (m, 4H), 2.58 (t, J=6.8 Hz, 2H), 2.68 (t, J=6.8 Hz, 2H), 3.38 (s, 3H), 3.61 (s, 2H), 3.62-3.72 (m, 1H), 3.95-4.00 (m, 4H), 4.08-4.22 (m, 1H), 6.44 (d, J=7.3 Hz, 1H), 6.68 (d, J=2.7 Hz, 1H), 6.75 (dd, J=9.0 and 2.7 Hz, 1H), 6.95 (d, J=7.3 Hz, 1H), 7.17 (d, J=9.0 Hz, 1H), 7.25-7.27 (m, 2H), 7.45-7.52 (m, 2H), 7.60-7.70 (m, 1H), 8.40 (d, J=7.9 Hz, 1H), 8.48 (d, J=1.5 Hz, 2H). 
       Example 27 
     Synthesis of 1-ethyl-3,3,5-trimethyl-7-(3-((3-(1-oxoisoquinolin-2(2H)-yl)propyl)(pyridin-4-ylmethyl)amino)propoxy)-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione dihydrochloride 
       [1675]    A 4N-hydrogen chloride in ethyl acetate solution (0.3 ml) was added to an ethyl acetate solution (3 ml) of 1-ethyl-3,3,5-trimethyl-7-(3-((3-(1-oxoisoquinolin-2(2H)-yl)propyl)(pyridin-4-ylmethyl)amino)propoxy)-1H-benzo[b][1,4]diazepine-2,4(3H, 5H)-dione (159 mg), and the mixture was stirred at room temperature for two hours. The reaction mixture was condensed under reduced pressure to give the title compound (178 mg) as a amorphous solid. 
         [1676]      1 H-NMR (DMSO-d 6 ) δ ppm: 0.74 (s, 3H), 1.00 (t, J=7.0 Hz, 3H), 1.32 (s, 3H), 2.25 (br, 4H), 3.01-3.31 (m, 4H), 3.31 (s, 3H), 3.61-3.70 (m, 1H), 4.00-4.12 (m, 5H), 4.61 (br, 2H), 6.65 (d, J=7.4 Hz, 1H), 6.86-6.91 (m, 2H), 7.39 (d, J=8.9 Hz, 1H), 7.47-7.53 (m, 2H), 7.65-7.74 (m, 2H), 8.08 (br, 2H), 8.21 (d, J=8.0 Hz, 1H), 8.80 (br, 2H). 
       Pharmacological Test 1 
     (1) Production of Human Kv1.5-Expressing CHO-K1 Cell Lines 
       [1677]    CHO-K1 cell lines stably expressing human Kv1.5 channels were prepared in the following manner. 
         [1678]    Full-length human Kv1.5 cDNA was cloned from a human heart cDNA library (produced by Stratagene). The obtained human Kv1.5 sequence corresponds to the sequence described in FASEB J. 5, 331-337 (1991). 
         [1679]    The obtained human Kv1.5 cDNA was inserted into a plasmid encoding a CMV promoter and a G418 resistance marker to produce a Kv1.5 expression vector. The human Kv1.5 expression vector was transfected into CHO-K1 cells by the lipofectamine method. After culturing the cells in an F-12 medium (produced by Invitrogen Corp.) containing 10% FBS (produced by Invitrogen Corp.) for 3 or 4 days, the medium was replaced with a FBS-containing F-12 medium that included 1,000 μg/ml of G418 (produced by Invitrogen Corp.), and single colonies were isolated. The amount of Kv1.5 channel expression in the single colonies was quantified at the mRNA level by RT-PCR and then quantified at the protein level by western blotting. Finally, the expressed current was analyzed by patch clamp method. Cell lines expressing a current of 200 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamp method. 
       (2) Production of CHO Cell Line Expressing Human GIRK1/4 
       [1680]    CHO cell lines stably expressing human GIRK1/4 channels were prepared in the following manner. 
         [1681]    Full-length human GIRK1 cDNA was cloned from HuH cell- and HeLa cell-derived cDNA libraries. Full-length GIRK4 cDNA was amplified from a human heart cDNA library (produced by Clontech Laboratories, Inc.) by PCR using synthetic primers shown in Table 1, and cloned into the Eco-RI restriction enzyme site of pCR-Blunt (produced by Invitrogen Corporation) or into the HindII site of pUC118 (produced by Takara Bio, Inc.). 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Primer 
                 Sequence 
                   
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 hGIRK1-S 
                 5′-ATGTCTGCACTCCGAAGGAAATTTG-3′ 
                 SEQ ID No. 1 
               
               
                   
               
               
                 hGIRK1-A 
                 5′-TTATGTGAAGCGATCAGAGTTC-3′ 
                 SEQ ID No. 2 
               
               
                   
               
               
                 hGIRK1-F2 
                 5′-GCAGGGTACCCCTTCGTATTATGTCTGCACTCC-3′ 
                 SEQ ID No. 3 
               
               
                   
               
               
                 hGIRK1-A3 
                 5′-GGTGTCTGCCGAGATTTGA-3′ 
                 SEQ ID No. 4 
               
               
                   
               
               
                 hGIRK1-A4 
                 5′-CCGAGTGTAGGCGATCACCC-3′ 
                 SEQ ID No. 5 
               
               
                   
               
               
                 hGIRK4-S 
                 5′-ATGGCTGGCGATTCTAGGAATGCC-3′ 
                 SEQ ID No. 6 
               
               
                   
               
               
                 hGIRK4-A 
                 5′-TCTCACCGAGCCCCTGGCCTCCC-3′ 
                 SEQ ID No. 7 
               
               
                   
               
               
                 hGIRK4-S2 
                 5′-AACCAGGACATGGAGATTGG-3′ 
                 SEQ ID No. 8 
               
               
                   
               
               
                 hGIRK4-A2 
                 5′-GAGAACAGGAAAGCGGACAC-3′ 
                 SEQ ID No. 9 
               
               
                   
               
             
          
         
       
     
         [1682]    The obtained human GIRK1 and GIRK4 cDNA sequences correspond to known sequences (NCBI database: GIRK1 (NM — 002239) and GIRK4 (NM — 000890) respectively). The obtained GIRK1 and GIRK4 cDNA sequences were cloned into the Eco-RI restriction enzyme site of pCR-Blunt (available from Invitrogen Corporation) or into the HincII site of pUC118 (available from Takara Bio, Inc.). A GIRK4 expression vector was constructed by insertion into the BamHI-XhoI site of pcDNA5/FRT. A GIRK1 expression vector was constructed by insertion into the KpnI-XhoI site of pcDNA3.1 (+) or pCAG_neo. FLP-IN-CHO cells (produced by Invitrogen Corporation) were transfected with human GIRK1 and GIRK4 expression vectors by using Lipofectamine 2000 (produced by Invitrogen Corporation) according to the protocol enclosed with the reagent or using an electronic induction method (“Nucleofector Kit-T”, produced by Amaxa). First, the cells transfected with the GIRK4 expression vector were cultured in a 10% serum-containing F12 medium (produced by Sigma) supplemented with 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. Then the cells expressing GIRK4 were transfected with the GIRK1 expression vector and were cultured in 10% serum-containing F12 medium supplemented with 350 μg/ml of G418 and 600 μg/ml of hygromycin in an incubator with 5% carbon dioxide at 37° C. to select GIRK1/4 expressing cell lines. Cell populations whose growth was observed after about 2 weeks were isolated using cloning rings, and the obtained single colonies were proliferated. RNA was extracted from single colonies, and single-stranded cDNA was synthesized by a cDNA synthesis kit (produced by Invitrogen Corporation), and the amount of expression was quantified at the mRNA level by real-time PCR (Applied Biosystems, Ltd.). Finally, the expressed current was analyzed by patch clamp method described below. The cell lines expressing a current of 500 pA or more per cell were selected as channel-expressing cell lines for activity measurement by patch clamping method. 
       (3) Measurement of Ion Channel Current by Patch Clamp Method (Human Kv1.5-Expressing CHO-K1 Cell Line) 
       [1683]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolated table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human Kv1.5-expressing cells were cultured was placed in the perfusion chamber. 
         [1684]    Depolarizing stimulation pulses were applied and ionic current was recorded by using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, produced by HEKA) and a personal computer (manufactured by IBM Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, produced by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1685]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   40 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose 
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1686]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1687]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate 
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (4) Measurement of Ion Channel Current by Patch Clamp Method (Human GIRK1/4-Expressing CHO-K1 Cell Line) 
       [1688]    An experiment was carried out using a patch clamp setup at room temperature (20 to 26° C.). A perfusion chamber having a diameter of 20 mm (flow rate: about 5 ml/min) was mounted on the stage of a phase-contrast inverted microscope (produced by Nikon Corporation) placed on a vibration isolation table. A poly-L-lysine (produced by Sigma)-coated coverslip (diameter: 15 mm, produced by Matsunami Glass Ind., Ltd.) on which human GIRK1/4-expressing cells were cultured was placed in the perfusion chamber. 
         [1689]    Hyperpolarizing stimulation pulses were applied and ionic current was recorded using a patch clamp amplifier (EPC-7 or EPC-7 PLUS, manufactured by HEKA) and a personal computer (manufactured by IBM. Corp.) in which software for data acquisition and analysis of ion channel current (PULSE 8.77, manufactured by HEKA) was installed. The current was measured in the whole-cell configuration of the patch-clamp technique. The tip (resistance: 2 to 4 MΩ) of a borosilicate glass pipette (produced by Sutter Instrument Co.) was gently placed on the cell membrane by using a three-dimensional mechanical micromanipulator (produced by Shoshin EM Corporation). Weak suction resulted in giga seal formation (the pipette resistance increased to more than 1 GΩ). Subsequently, stronger suction was applied to break the cell membrane. The capacitative current derived from the cell membrane was corrected using a patch clamp amplifier. Subsequently, the series resistance (Rs) between the pipette and the interior of the cell was measured and corrected. 
         [1690]    The composition of the extracellular solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 NaCl 
                  140 mM, 
               
               
                   
                 KCl 
                   4 mM, 
               
               
                   
                 CaCl 2   
                  1.8 mM, 
               
               
                   
                 MgCl 2   
                   1 mM, 
               
               
                   
                 NaH 2 PO 4   
                 0.33 mM, 
               
               
                   
                 HEPES 
                   5 mM 
               
               
                   
                 Glucose 
                  5.5 mM (pH = 7.4) 
               
               
                   
                   
               
             
          
         
       
     
         [1691]    Each test compound was prepared as a 1000-fold concentrated stock solution that was dissolved in DMSO and then diluted in the extracellular solution. 
         [1692]    The composition of the electrode internal solution used is shown below. Unless otherwise specified, these components were obtained from Wako Pure Chemical Industries, Ltd. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 KOH 
                 100 mM, 
               
               
                   
                 KCl 
                  40 mM, 
               
               
                   
                 Aspartic acid 
                  70 mM, 
               
               
                   
                 MgCl 2   
                  1 mM, 
               
               
                   
                 MgATP 
                  5 mM, 
               
               
                   
                 K 2  creatine phosphate 
                  5 mM, 
               
               
                   
                 HEPES 
                  5 mM 
               
               
                   
                 EGTA 
                  5 mM (pH = 7.2) 
               
               
                   
                   
               
             
          
         
       
     
       (5) Measurement of Human Kv1.5 Current 
       [1693]    While the membrane potential was holded at −80 mV, depolarizing pulses (−80 mV for 0.05 seconds→□□+40 mV for 0.2 seconds→□□−40 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure Kv1.5 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and holding the membrane potential at −80 mV, depolarizing pulses were applied. The current obtained during the pulse application was recorded as a current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and holding the membrane potential at −80 mV, depolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration was recorded. 
         [1694]    The data was analyzed by using the step end current recorded during the +40 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the +40 mV depolarizing pulse stimulation. 
         [1695]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (6) Measurement of Human GIRK1/4 Current 
       [1696]    While the membrane potential was holded at −80 mV, hyperpolarizing pulses (−80 mV for 0.05 seconds→□□−120 mV for 0.2 seconds→□□−80 mV for 0.05 seconds) were applied at a stimulation frequency of 1 Hz to measure GIRK1/4 channel current. More specifically, first, while perfusing an extracellular solution containing 0.1% DMSO and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. The current obtained during the pulse application was recorded as the current in the absence of the test compounds. Subsequently, while perfusing an extracellular solution containing 0.1 μM of a test compound and maintaining the membrane potential at −80 mV, hyperpolarizing pulses were applied. After the inhibitory effect of the test compound had been stabilized, the current was recorded. The same procedure was repeated using an extracellular solution containing 1 μM of the test compound and then using an extracellular solution containing 10 μM of the test compound. The current obtained using the solution containing the test compound at each concentration were recorded. 
         [1697]    The data was analyzed by using the step end current recorded during the −120 mV depolarizing stimulation. The “step end current” refers to the average current flowing for a period of 195 to 199 milliseconds from the start of the −120 mV depolarizing pulse stimulation. 
         [1698]    Using the step end current in the presence of the test compound and the step end current in the absence of the test compound, the relative current in the solution containing the test compound at each concentration was calculated according to the following formula: 
         [0000]      Relative current=(Step end current in the presence of the test compound)/(Step end current in the absence of the test compound) 
       (7) Calculation of Inhibitory Activity on Kv1.5 Channel Ionic Current and GIRK1/4 Channel Current 
       [1699]    The concentration for 50% inhibition of Kv1.5 channel current or GIRK1/4 channel current (IC 50  value) was calculated according to the following nonlinear regression equation: 
         [0000]      Relative current=1/(1+[Concentration of the compound]/IC 50 ) nH    
         [0000]    wherein nH is the Hill coefficient. 
         [1700]    Table 2 shows the test results. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Test Compound 
                 KV1.5 IC 50  (μM) 
               
               
                   
                   
               
             
             
               
                   
                 Compound of Example 2 
                 1.10 
               
               
                   
                 Compound of Example 5 
                 0.87 
               
               
                   
                 Compound of Example 6 
                 0.60 
               
               
                   
                 Compound of Example 14 
                 0.40 
               
               
                   
                 Compound of Example 20 
                 0.34 
               
               
                   
                 Compound of Example 21 
                 0.84 
               
               
                   
                 Compound of Example 22 
                 1.50