Patent Publication Number: US-2007105890-A1

Title: Novel condensed imidazole derivative

Description:
TECHNICAL FIELD  
      The present invention relates to novel cyclic imidazole derivatives useful as medicines. More particularly, it relates to novel cyclic imidazole derivatives effective as a dipeptidyl peptidase IV (DPP-IV) inhibitor. Furthermore, it relates to a pharmaceutical composition for the treatment of diabetes containing a novel cyclic imidazole derivative effective as a dipeptidyl peptidase IV (DPP-IV) inhibitor, as an active ingredient.  
     BACKGROUND ART  
      DPP-IV is a serine protease widely present in the body, is one of dipeptidyl aminopeptidases capable of hydrolyzing and releasing a N-terminal dipeptide, and markedly acts on, in particular, peptides containing proline as the second amino acid from the N-terminal. Therefore, DPP-IV is referred to also prolyl endopeptidase. DPP-IV is known to accept, as substrates, various biological peptides concerned in the endocrine system, the neuroendocrine system, immune functions and the like. It is known that many physiologically active peptides such as the pancreatic polypeptide family represented by pancreatic polypeptides (PP), neuropeptide Y (NPY) and the like; the glucagon/VIP family represented by vasoactive intestinal polypeptides (VIP), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptides (GIP), growth hormone release accelerating factor (GRF) and the like; and the chemocaine family are substrates for DPP-IV and feel the influences of DPP-IV, such as activation/inactivation, metabolism acceleration and the like (J. Langner and S. Ansorge, “Cellular Peptidases in Immune Functions and Disease 2”, Advances in Experimental Medicine and Biology Vol. 477).  
      DPP-IV severs two amino acids (His-Ala) from the N-terminal of GLP-1. It is known that although the severed peptide binds weekly to a GLP-1 receptor, it has no activating effect on the receptor and acts as an antagonist (L. B. Knudsen et al., European Journal of Pharmacology, Vol. 318, p429-435, 1996). The metabolism of GLP-1 by DPP-IV in blood is known to be very rapid, and the concentration of active GLP-1 in blood is increased by the inhibition of DPP-IV (T. J. Kieffer et al., Endocrinology, Vol. 136, p3585-3596, 1995). GLP-1 is a peptide secreted from intestinal tract by the ingestion of sugars and is a main accelerating factor for the glucose-responsive secretion of insulin by pancreas. In addition, GLP-1 is known to have accelerating effect on insulin synthesis in pancreatic β cells and accelerating effect on β cell proliferation. Moreover, it is known that GLP-1 receptors appear also in digestive tracts, liver, muscle, adipose tissue and the like, and it is also known that in these tissues, GLP-1 affects working of digestive tracts, the secretion of acid in stomach, the synthesis and degradation of glycogen, insulin-dependent glucose uptake, and the like. Accordingly, there is expected the development of a DPP-IV inhibitor effective against type 2 diabetes (non-insulin-dependent diabetes) which brings about effects such as the acceleration of insulin secretion dependent on blood sugar level, the improvement of pancreas function, the improvement of a high postprandial blood sugar level, the improvement of glucose tolerance abnormality, the improvement of insulin resistance, and the like, by increasing the concentration of GLP-1 in blood (R. A. Pederson et al., Diabetes Vol. 47, p1253-1258, 1998).  
      Various DPP-IV inhibitors have been reported. For example, International Publication No. WO02/02560 pamphlet reports that xanthine derivatives having a piperazine ring or the like are effective as a DPP-IV inhibitor. International Publication No. WO02/068420 pamphlet and International Publication No. WO03/004496 pamphlet report that xanthine derivatives having a piperidine ring or the like are effective as a DPP-IV inhibitor. International Publication No. WO03/024965 pamphlet reports that xanthine derivatives containing a 2-aminocyclohexylamino group are effective as a DPP-IV inhibitor. International Publication No. WO02/024698 pamphlet reports that xanthine derivatives are effective as a phosphodiesterase V inhibitor.  
     DISCLOSURE OF THE INVENTION  
      An object of the present invention is to provide a novel compound having an excellent DPP-IV inhibitory activity.  
      The present inventors earnestly investigated in order to achieve the above object, and consequently found that the following compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug (if necessary, they are hereinafter abbreviated as the present inventive compound in some cases) has an excellent DPP-IV inhibitory effect, whereby the present invention has been accomplished.  
      That is, the present invention relates to the following: 
 
 [1] A compound represented by the formula (I):  
                 
 
 wherein R 1  is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group; 
 
      R 2  and R 3  are independently a hydrogen atom, a halogen atom, a cyano group, a formyl group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkyloxy group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted amino group, an optionally substituted carbamoyl group, a carboxyl group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyl group, an optionally substituted aryl group, an optionally substituted aryloxy group, an optionally substituted aryloxycarbonyl group, an optionally substituted aralkyl group, an optionally substituted aralkyloxy group, an optionally substituted aroyl group, an optionally substituted arylthio group, an optionally substituted arylsulfinyl group, an optionally substituted arylsulfonyl group, an optionally substituted alkylthio group, an optionally substituted alkylsulfinyl group, an optionally substituted alkylsulfonyl group, an optionally substituted heteroaryl group, an optionally substituted heteroarylalkyl group, an optionally substituted heteroarylcarbonyl group, an optionally substituted heteroaryloxy group, an optionally substituted alkylcarbonyl group, an optionally substituted nitrogen-containing saturated heterocyclic group, an optionally substituted aralkyloxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  is a hydrogen atom, an alkyl group, an alkenyl group, a cycloalkyl group or an alkoxy group, and R 19  is an optionally substituted alkyl group, an optionally substituted alkenyl group, a cycloalkyl group, a cycloalkyloxy group, an optionally substituted alkoxy group, an optionally substituted alkenyloxy group, a 2-indanyloxy group, a 5-indanyloxy group or an optionally substituted aryloxy group, or R 2  and R 3  may be taken together to form an oxo group on the ring;  
      R 4  and R 5  are independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group or an alkoxycarbonylmethyl group;  
      R 3  and R 5  may be taken together to form a double bond on the ring;  
      R 2 , R 3 , R 4  and R 5  may form an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring together with the adjacent carbon atoms;  
      R 6  is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted vinyl group, an optionally substituted nitrogen-containing saturated heterocyclic group or an optionally substituted heteroaryl group; and  
      —Y—NH 2  is a group represented by the following formula (A) or a group represented by the following formula (B):  
                 
 
 wherein m is 0, 1 or 2, and R 7  is absent or one or two R 7 s are present and are independently a halogen atom, a hydroxyl group, an oxo group, an optionally substituted alkoxy group, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted amino group, a carboxyl group, an optionally substituted alkoxycarbonyl group or an optionally substituted carbamoyl group, or two R 7 s, when taken together, represent methylene or ethylene and may bind to two carbon atoms constituting the ring, to form a new ring, or  
                 
 
 wherein n is 0, 1 or 2, and R 8  is absent or one or two R 8 s are present and are independently a halogen atom, a hydroxyl group, an oxo group, an optionally substituted alkoxy group, an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, an optionally substituted amino group, a carboxyl group, an optionally substituted alkoxycarbonyl group or an optionally substituted carbamoyl group, or two R 8 s, when taken together, represent methylene or ethylene and may bind to two carbon atoms constituting the ring, to form a new ring, 
 
 a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [2] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [1], wherein —Y—NH 2  is a group represented by the formula (A) and m is 1 or 2, or —Y—NH 2  is a group represented by the formula (B) and n is 1 or 2. 
 
 [3] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [1] or [2], wherein R 2  and R 3  are taken together to form an oxo group on the ring. 
 
 [4] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [1] or [2], wherein R 3  and R 5  are taken together to form a double bond on the ring. 
 
 [5] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [1] or [2], wherein R 2 , R 3 , R 4  and R 5  form an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring together with the adjacent carbon atoms. 
 
 [6] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [4], wherein R 2  is a hydrogen atom, a cyano group, an optionally substituted alkyl group, a carboxyl group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aryloxy group, an optionally substituted aryloxycarbonyl group, an optionally substituted aralkyl group, an optionally substituted aralkyloxy group, an optionally substituted aroyl group, an optionally substituted alkylcarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]. 
 
 [7] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [4], wherein R 4  is a hydrogen atom or a methyl, ethyl or alkoxycarbonylmethyl group. 
 
 [8] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [4], wherein R 2  is a hydrogen atom, a cyano group, an optionally substituted alkyl group, a carboxyl group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aryloxy group, an optionally substituted aryloxycarbonyl group, an optionally substituted aralkyl group, an optionally substituted aralkyloxy group, an optionally substituted aroyl group, an optionally substituted alkylcarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]; and R 4  is a hydrogen atom or a methyl, ethyl or alkoxycarbonylmethyl group. 
 
 [9] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [8], wherein R 6  is a group represented by the following formula (C), (D) or (E):  
                 
 
 wherein Z is an oxygen atom, —S(O) p — or —N(R 14 )—, 
 
      R 9  is absent or one or two R 9 s are present and are independently a halogen atom, a hydroxyl group, a formyl group, a carboxyl group, a cyano group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an alkyl group, a haloalkyl group, a cycloalkyl group, an alkoxy group, a haloalkoxy group, an optionally substituted amino group, an optionally substituted carbamoyl group, an alkoxycarbonyl group, an optionally substituted alkylcarbonyl group, a cycloalkylcarbonyl group, an optionally substituted aryl group, or an optionally substituted heteroaryl group, or two R 9 s, when taken together, represent a C 1-3  alkylenedioxy group,  
      R 10  is absent or one or two R 10 s are present and are independently a halogen atom, a cyano group, an alkyl group, a haloalkyl group, a cycloalkyl group, an alkoxy group or a haloalkoxy group,  
      R 11  is methyl, ethyl, a chlorine atom or a bromine atom,  
      R 12  is a hydrogen atom, methyl, ethyl, a chlorine atom or a bromine atom,  
      R 13  is a hydrogen atom, methyl or ethyl,  
      p is 0, 1 or 2, and  
      R 14  is a hydrogen atom or an alkyl group.  
      [10] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [9], wherein R 6  is the formula (C) or the formula (E).  
      [11] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [10], wherein R 6  is the formula (C), and R 9  is absent or one or two R 9 s are present and are independently a halogen atom, a cyano group, an alkylthio group, an alkylsulfonyl group, a C 1-3  alkylenedioxy group, an alkyl group, a haloalkyl group, a cycloalkyl group, an alkoxy group, a haloalkoxy group, an alkoxycarbonyl group, an alkylcarbonyl group, a haloalkylcarbonyl group or a cycloalkylcarbonyl group. 
 
 [12] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [8], wherein R 6  is the following formula (F):  
                 
 
 wherein R 15  is a halogen atom, a cyano group, an alkyl group, a haloalkyl group, a cycloalkyl group, an alkoxy group or a haloalkoxy group, and R 16  is a hydrogen atom or a fluorine atom. 
 
 [13] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [12], wherein R 1  is a hydrogen atom or an optionally substituted alkyl group of 1 to 3 carbon atoms whose substituent(s) is selected from fluorine atom, optionally substituted aroyl groups, carboxyl group, optionally substituted alkoxycarbonyl groups, optionally substituted aryl groups and optionally substituted aryloxy groups. 
 
 [14] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [12], wherein R 1  is a group represented by the formula: —Ra—Rb-Rc in which 
 
      Ra is an alkylene chain,  
      Rb is a single bond or a carbonyl group, and  
      Rc is an optionally substituted alkyl group, an optionally substituted alkoxy group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aryloxy group or an optionally substituted heteroaryloxy group.  
      [15] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [12], wherein R 1  is a hydrogen atom, methyl or ethyl.  
      [16] A compound according to [1], which is represented by the formula (II):  
                 
 
 wherein R 4  is as defined in [1]; R 15  and R 16  are as defined in [12]; R 1a  is a hydrogen atom, methyl or the formula: —Ra—Rb-Rc wherein Ra, Rb and Rc are as defined in [14]; and R 2a  is a cyano group, a carboxyl group, an oxazolyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, a tetrahydro-furanyloxycarbonyl group, an optionally substituted aryloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1], a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [17] A compound according to [1], which is represented by the formula (III):  
                 
 
 wherein R 16  is as defined in [12]; R 1a  and R 2a  are as defined in [16]; and R 15a  is a chlorine atom, a bromine atom, an iodine atom, a cyano group, methyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy or trifluoromethoxy, a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [18] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [17], wherein R 1a  is a hydrogen atom. 
 
 [19] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [17] or [18], wherein R 2a  is a carboxyl group, an optionally substituted alkoxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]. 
 
 [20] A compound according to [1], which is represented by the formula (IV):  
                 
 
 wherein R 1 , R 6  and Y are as defined in [1]; and the ring A is an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring, 
 
 a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [21] A compound according to [1], which is represented by the formula (V):  
                 
 
 wherein R 1  is as defined in [1]; R 16  is as defined in [12]; R 15a  is as defined in [17]; and A is as defined in [20], a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [22] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [21], wherein R 1  is a hydrogen atom or methyl. 
 
 [23] A compound according to [1], which is represented by the formula (VI):  
                 
 
 wherein R 1  is as defined in [1]; R 16  is as defined in [12]; R 15a  is as defined in [17]; and R 17  is absent or one to four R 17 s are present and are independently a hydroxyl group, a halogen atom, a cyano group, a carboxyl group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkyloxy group, an optionally substituted alkenyl group, an optionally substituted carbamoyl group, an optionally substituted alkoxy group, an optionally substituted alkoxycarbonyl group, an optionally substituted aryloxycarbonyl group, an optionally substituted alkylcarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, an optionally substituted aralkyloxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1], 
 
 a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug. 
 
 [24] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [23], wherein R 1  is a hydrogen atom, methyl or the formula: —Ra—Rb-Rc wherein Ra, Rb and Rc are as defined in [14]. 
 
 [25] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [23], wherein R 1  is methyl. 
 
 [26] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [25], wherein R 17  is a fluorine atom, a chlorine atom, a cyano group, a carboxyl group, acetyl, dimethylcarbamoyl, diethylcarbamoyl, methyl, ethyl, isopropyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, difluoromethoxy, trifluoromethoxy, an alkoxyalkyl group optionally substituted by a halogen atom or a hydroxyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]. 
 
 [27] A compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to [25], wherein R 17  is a fluorine atom, a cyano group, a carboxyl group, an alkoxymethyl group optionally substituted by a halogen atom, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, a tetrahydrofuranyloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]. 
 
 [28] A dipeptidyl peptidase IV inhibitor comprising a compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [27] as an active ingredient. 
 
 [29] A pharmaceutical composition for the treatment of diabetes comprising a compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [27] as an active ingredient. 
 
 [30] Use of a compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [27] in the manufacture of a dipeptidyl peptidase IV inhibitor. 
 
 [31] Use of a compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [27] in the manufacture of a pharmaceutical composition for the treatment of diabetes. 
 
 [32] A method for treating diabetes comprising administering an effective amount of a compound, a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug according to any one of [1] to [27] to a patient who needs treatment. 
 
      The present inventive compound has an excellent DPP-IV inhibitory activity and is useful as a therapeutic agent for diabetes. 
    
    
     BEST MODE FOR CARRYING OUT THE INVENTION  
      The present invention is explained below in further detail.  
      In the present specification, the number of substituents of each group defined by the term “optionally substituted” or “substituted” is not particularly limited so long as the substitution is possible, and it is 1 or more. Unless otherwise specified, the explanation of each group applies also to the case where the group is a portion or the substituent of another group.  
      The “halogen atom” includes, for example, fluorine atom, chlorine atom, bromine atom and iodine atom.  
      The “alkyl group” includes, for example, linear or branched alkyl groups of 1 to 6 carbon atoms. Specific examples thereof are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Preferable examples thereof are linear or branched alkyl groups of 1 to 4 carbon atoms. Specific examples of such groups are methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, etc.  
      The “alkenyl group” includes, for example, alkenyl groups of 2 to 6 carbon atoms. Specific examples thereof are vinyl, propenyl, methylpropenyl, butenyl, methylbutenyl, etc.  
      The “alkynyl group” includes, for example, alkynyl groups of 2 to 6 carbon atoms. Specific examples thereof are ethynyl, 1-propynyl, 2-propynyl, butynyl, pentynyl, hexynyl, etc.  
      The “cycloalkyl group” includes, for example, cycloalkyl groups of 3 to 10 carbon atoms. Specific examples thereof are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl, etc. Preferable examples thereof are cycloalkyl groups of 3 to 6 carbon atoms. Specific examples of such groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.  
      The “aryl group” includes, for example, aryl groups of 6 to 10 carbon atoms. Specific examples thereof are phenyl, 1-naphthyl, 2-naphthyl, etc.  
      The “aralkyl group” includes, for example, groups formed by bonding of an aryl group to an alkylene chain. Specific examples thereof are benzyl, 2-phenylethyl, 1-naphthylmethyl, etc.  
      The “alkylene chain” includes, for example, alkylene chains of 1 to 3 carbon atoms. Specific examples thereof are methylene, ethylene, trimethylene, etc.  
      The “heteroaryl group” includes, for example, 5- to 10-membered monocyclic or polycyclic groups containing one or more (for example, 1 to 4) heteroatoms selected from nitrogen atom, sulfur atom and oxygen atom. Specific examples thereof are pyrrolyl, thienyl, benzothienyl, benzofuranyl, benzoxazolyl, benzothiazolyl, furyl, oxazolyl, thiazolyl, isoxazolyl, imidazolyl, pyrazolyl, pyridyl, pyrazyl, pyrimidyl, pyridazyl, quinolyl, isoquinolyl, triazolyl, triazinyl, tetrazolyl, indolyl, imidazo[1,2-a]pyridyl, dibenzofuranyl, benzimidazolyl, quinoxalyl, cinnolyl, quinazolyl, indazolyl, naphthyridyl, quinolinolyl, isoquinolinolyl, etc. Preferable examples thereof are 5-or 6-membered groups containing a heteroatom selected from nitrogen atom, sulfur atom and oxygen atom. Specific examples of such groups are pyridyl, thienyl, furyl, etc.  
      The heteroaryl portion of the “heteroarylalkyl group” includes the groups exemplified above as the heteroaryl group.  
      The “alkylcarbonyl group” includes, for example, alkylcarbonyl groups of 2 to 4 carbon atoms. Specific examples thereof are acetyl, propionyl, butyryl, etc.  
      The “cycloalkylcarbonyl group” includes, for example, cycloalkylcarbonyl groups of 4 to 11 carbon atoms. Specific examples thereof are cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, adamantylcarbonyl, norbornylcarbonyl, etc. Preferable examples thereof are cycloalkylcarbonyl groups of 4 to 7 carbon atoms. Specific examples of such groups are cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc  
      The “aroyl group” includes, for example, aroyl groups of 7 to 11 carbon atoms. Specific examples thereof are benzoyl, 1-naphthoyl, 2-naphthoyl, etc.  
      The heteroaryl portion of the “heteroarylcarbonyl group” includes the groups exemplified above as the heteroaryl group.  
      The “alkoxycarbonyl group” includes, for example, alkoxycarbonyl groups of 2 to 5 carbon atoms. Specific examples thereof are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, 2-propoxycarbonyl, tert-butoxycarbonyl, etc.  
      The “aryloxycarbonyl group” includes, for example, aryloxycarbonyl groups of 7 to 11 carbon atoms. Specific examples thereof are phenyloxycarbonyl, 2-naphthyloxycarbonyl, 1-naphthyloxycarbonyl group, etc.  
      The “alkoxy group” includes, for example, alkoxy groups of 1 to 4 carbon atoms. Specific examples thereof are methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.  
      The “cycloalkyloxy group” includes, for example, cycloalkyloxy groups of 3 to 10 carbon atoms. Specific examples thereof are cyclopropyloxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, adamantyloxy, norbornyloxy, etc. Preferable examples thereof are cycloalkyloxy groups of 3 to 6 carbon atoms. Specific examples of such groups are cyclopropyloxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, etc.  
      The cycloalkyloxy portion of the “cycloalkyloxycarbonyl group” includes the groups exemplified above as the cycloalkyloxy group.  
      The “aryloxy group” includes, for example, aryloxy groups of 6 to 10 carbon atoms. Specific examples thereof are phenoxy, 1-naphthyloxy, 2-naphthyloxy, etc.  
      The aralkyl portion of the “aralkyloxy group” includes the groups exemplified above as the aralkyl group. Specific examples thereof are benzyloxy, 2-phenylethyloxy, etc.  
      The aralkyl portion of the “aralkyloxycarbonyl group” includes the groups exemplified above as the aralkyl group.  
      The heteroaryl portion of the “heteroaryloxy group” includes the groups exemplified above as the heteroaryl group.  
      The “alkylthio group” includes, for example, alkylthio groups of 1 to 6 carbon atoms. Specific examples thereof are methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, tert-butylthio, pentylthio, hexylthio, etc. Preferable examples thereof are alkylthio groups of 1 to 4 carbon atoms. Specific examples of such groups are methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, tert-butylthio, etc.  
      The “alkylsulfinyl group” includes, for example, alkylsulfinyl groups of 1 to 6 carbon atoms. Specific examples thereof are methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, pentylsulfinyl, hexylsulfinyl, etc. Preferable examples thereof are alkylsulfinyl groups of 1 to 4 carbon atoms. Specific examples of such groups are methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, etc.  
      The “alkylsulfonyl group” includes, for example, alkylsulfonyl groups of 1 to 6 carbon atoms. Specific examples thereof are methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc. Preferable examples thereof are alkylsulfonyl groups of 1 to 4 carbon atoms. Specific examples of such groups are methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, etc.  
      The “arylthio group” includes, for example, arylthio groups of 6 to 10 carbon atoms. Specific examples thereof are phenylthio, 1-naphthylthio, 2-naphthylthio, etc.  
      The “arylsulfinyl group” includes, for example, arylsulfinyl groups of 6 to 10 carbon atoms. Specific examples thereof are phenylsulfinyl, 1-naphthylsulfinyl, 2-naphthylsulfinyl, etc.  
      The “arylsulfonyl group” includes, for example, arylsulfonyl groups of 6 to 10 carbon atoms. Specific examples thereof are phenylsulfonyl, tosyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl, etc.  
      The “nitrogen-containing saturated heterocyclic group” includes, for example, 5-or 6-membered saturated heterocyclic groups which have one or two nitrogen atoms and may further have an oxygen atom or a sulfur atom. Specific examples thereof are pyrrolidinyl, imidazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, hexamethyleniminyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, oxoimidazolidinyl, dioxoimidazolidinyl, oxooxazolidinyl, dioxooxazolidinyl, dioxothiazolidinyl, tetrahydrofuranyl, tetrahydropyridinyl, etc.  
      The substituent(s) of the “optionally substituted alkyl group” includes, for example, (1) halogen atoms, (2) hydroxyl group, (3) cyano group, (4) carboxyl group, (5) optionally substituted cycloalkyl groups, (6) optionally substituted aryl groups, (7) optionally substituted heteroaryl groups, (8) optionally substituted aroyl groups, (9) optionally substituted heteroarylcarbonyl groups, (10) optionally substituted arylaminocarbonyl groups, (11) optionally substituted heteroarylaminocarbonyl groups, (12) optionally substituted aryloxy groups, (13) optionally substituted arylsulfonyl groups, (14) optionally substituted aralkylsulfonyl groups, (15) optionally substituted alkoxy groups, (16) optionally substituted cycloalkyloxy groups, (17) optionally substituted alkoxycarbonyl groups, (18) optionally substituted aryloxycarbonyl groups, (19) optionally substituted amino groups, (20) optionally substituted carbamoyl groups, (21) alkylsulfonyl groups, (22) optionally substituted alkylcarbonyl groups, (23) cycloalkyloxycarbonyl groups, (24) tetrahydrofuranyloxycarbonyl group, and (25) tetrahydrofuranyl group.  
      Here, the above items (1) to (25) are explained below.  
      The substituents of the “optionally substituted cycloalkyl groups” of the above item (5) include, for example, alkyl groups, aralkyl groups, alkoxy groups, alkoxycarbonyl groups and fluorine atom.  
      The substituents of the “optionally substituted aryl groups” of the above item (6) include those exemplified hereinafter as the substituent(s) of the “optionally substituted aryl group”.  
      The substituents of the “optionally substituted heteroaryl groups” of the above item (7) include, for example,  
      (a) hydroxyl group,  
      (b) halogen atoms,  
      (c) alkyl groups,  
      (d) alkyl groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (e) alkoxy groups,  
      (f) alkoxy groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (g) cyano group,  
      (h) carboxyl group,  
      (i) alkoxycarbonyl groups,  
      (j) carbamoyl groups which may be substituted by an alkyl group(s) (for example, carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl and diethylcarbamoyl),  
      (k) aryl groups,  
      and (l) amino group.  
      The substituents of the “optionally substituted aroyl groups” of the above item (8) include those exemplified as the substituents of the “optionally substituted aryl groups” of the above item (6).  
      The substituents of the “optionally substituted heteroarylcarbonyl groups” of the above item (9) include those exemplified as the substituents of the “optionally substituted heteroaryl groups” of the above item (7).  
      The substituents of the “optionally substituted arylaminocarbonyl groups” of the above item (10) include those exemplified as the substituents of the “optionally substituted aryl groups” of the above item (6).  
      The substituents of the “optionally substituted heteroarylaminocarbonyl groups” of the above item (11) include those exemplified as the substituents of the “optionally substituted heteroaryl groups” of the above item (7).  
      The substituents of the “optionally substituted aryloxy groups” of the above item (12) and the “optionally substituted arylsulfonyl groups” of the above item (13) include those exemplified as the substituents of the “optionally substituted aryl groups” of the above item (6).  
      The aralkyl portion of each of the “optionally substituted aralkylsulfonyl groups” of the above item (14) includes the groups exemplified above as the aralkyl group.  
      The substituents of the “optionally substituted aralkylsulfonyl groups” include those exemplified as the substituents of the “optionally substituted aryl groups” of the above item (6).  
      The substituents of the “optionally substituted alkoxy groups” of the above item (15) include, for example,  
      (a) hydroxyl group,  
      (b) carboxyl group,  
      (c) alkoxy groups,  
      (d) alkylcarbonyloxy groups (for example, methylcarbonyloxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, butylcarbonyloxy and tert-31′ butylcarbonyloxy),  
      (e) alkoxycarbonyl groups,  
      (f) amino groups which may be substituted by an alkyl group(s) (for example, amino, dimethylamino and diethylamino),  
      (g) carbamoyl groups substituted by an alkyl group(s),  
      (h) sulfamoyl groups substituted by an alkyl group(s),  
      (i) ureido groups substituted by an alkyl group(s),  
      (j) alkoxycarbonyloxy groups (for example, methoxycarbonyloxy, ethoxycarbonyloxy, 2-propoxycarbonyloxy and tert-butoxycarbonyloxy),  
      (k) cycloalkyloxycarbonyloxy groups (for example, cyclopentyloxycarbonyloxy, cyclohexyloxycarbonyloxy and cycloheptyloxycarbonyloxy),  
      (l) phenyl groups which may be substituted by a halogen atom or an alkoxy group (for example, phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-isopropoxyphenyl and 3-isopropoxyphenyl),  
      (m) 5-methyl-2-oxo-1,3-dioxolen-4-yl,  
      (n) 5-oxo-2-tetrahydrofuranyl,  
      (o) 1,3-dihydro-3-oxo-1-isobenzofuranyl,  
      (p) tetrahydrofuranyl,  
      (q) nitrogen-containing saturated heterocyclic groups,  
      (r) alkoxy groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (s) cycloalkyl groups,  
      (t) cycloalkyl groups substituted by a halogen atom or an alkoxy group (for example, 2-fluorocyclopropyl, 2-methoxycyclopropyl, 2-fluorocyclobutyl, 3-fluorocyclobutyl and 3-methoxycyclobutyl), and  
      (u) halogen atoms.  
      The substituents of the “optionally substituted cycloalkyloxy groups” of the above item (16) and the “optionally substituted alkoxycarbonyl groups” of the above item (17) include those exemplified as the substituents of the “optionally substituted alkoxy groups” of the above item (15).  
      The substituents of the “optionally substituted aryloxycarbonyl groups” of the above item (18) include those exemplified as the substituents of the “optionally substituted aryl groups” of the above item (6).  
      The substituents of the “optionally substituted amino groups” of the above item (19) include, for example,  
      (a) alkyl groups,  
      (b) alkylcarbonyl groups,  
      (c) aroyl groups,  
      (d) alkylsulfonyl groups,  
      (e) arylsulfonyl groups,  
      (f) optionally substituted aryl groups (whose substituent(s) includes, for example, halogen atoms, alkyl groups and alkoxy groups),  
      (g) alkoxycarbonylmethyl groups (the carbon atom of the methyl portion may be substituted by one or two alkyl groups, and the two alkyl groups on the carbon atom of the methyl portion may bind to each other to form cyclopropyl, cyclobutyl or cyclopentyl together with the carbon atom of the methyl portion), and (h) aralkyl groups.  
      As the optionally substituted amino groups, (i) imides are also exemplified.  
      The substituents of the “optionally substituted carbamoyl groups” of the above item (20) include, for example, alkyl groups and cycloalkyl groups. The two substituents of the carbamoyl group may bind to each other to form an aliphatic heterocyclic ring which may contain carbon, nitrogen or oxygen, such as pyrrolidine (which may be substituted by a hydroxyl group), piperidine, morpholine, thiomorpholine, thiomorpholine oxide, thiomorpholine dioxide, piperazine (whose nitrogen atom may be substituted by methyl or ethyl), or the like.  
      Specific examples of the “optionally substituted carbamoyl groups” are carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, diethylcarbamoyl, ethylmethylcarbamoyl, methylpropylcarbamoyl, cyclopropylcarbamoyl, cyclopropylmethylcarbamoyl, pyrrolidinocarbonyl, piperidinocarbonyl, morpholinocarbonyl, etc.  
      The substituents of the “optionally substituted alkylcarbonyl groups” of the above item (22) include, for example,  
      (a) halogen atoms,  
      (b) alkoxy groups,  
      (c) cycloalkyl groups,  
      (d) alkoxycarbonyl groups,  
      (e) optionally substituted aryl groups (whose substituent(s) include, for example, halogen atoms, alkyl groups, alkoxy groups and alkoxycarbonyl groups), and (f) hydroxyl group.  
      The substituent(s) of each of the “optionally substituted alkylthio group”, “optionally substituted alkylsulfinyl group” and “optionally substituted alkylsulfonyl group” includes those exemplified as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of the “optionally substituted alkenyl group” or the “optionally substituted alkynyl group” includes  
      (1) hydroxyl group,  
      (2) halogen atoms,  
      (3) alkyl groups,  
      (4) alkyl groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, methoxypropyl and ethoxypropyl),  
      (5) alkoxy groups,  
      (6) alkoxy groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (7) phenyl groups or aroyl groups, which may be substituted by the following (aa), (bb) or (cc):  
      (aa) an alkoxy group(s) which may be substituted by a halogen atom(s) or an alkoxy group (for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (bb) an alkyl group(s) which may be substituted by a halogen atom(s) (for example, methyl, ethyl, propyl, isopropyl, butyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl and 1-(difluoromethyl)-2,2-difluoroethyl), or  
      (cc) a halogen atom(s),  
      (8) cyano group,  
      (9) carboxyl group,  
      (10) optionally substituted alkoxycarbonyl groups (whose substituent(s) includes those exemplified as the substituents of (15) the “optionally substituted alkoxy groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”),  
      (11) carbamoyl groups which may be substituted by an alkyl group(s) (for example, carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl and diethylcarbamoyl),  
      (12) alkylsulfonyl groups,  
      and (13) phenyloxy group.  
      The substituent(s) of the “optionally substituted vinyl group” includes, for example, halogen atoms and alkyl groups.  
      Specific examples of the substituted vinyl groups are 1-propylene, 2-methyl-1-propylene, 2-chloro-1-propylene, etc.  
      The substituent(s) of the “optionally substituted ethynyl group” includes, for example, alkyl groups and cycloalkyl groups.  
      Specific examples of the substituted ethynyl groups are ethylidyne, propylidyne, 2-cyclopropyl-1-ethylidyne, etc.  
      The substituent(s) of the “optionally substituted cycloalkyl group” includes those exemplified as the substituents of (5) the “optionally substituted cycloalkyl groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of the “optionally substituted aryl group” includes, for example,  
      (1) hydroxyl group,  
      (2) halogen atoms,  
      (3) alkyl groups,  
      (4) alkyl groups substituted by a halogen atom(s), an alkoxy group or a cycloalkyl group (for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, methoxypropyl and ethoxypropyl),  
      (5) phenyl groups which may be substituted by the following (aa), (bb) or (cc):  
      (aa) an alkoxy group(s) which may be substituted by a halogen atom(s) or an alkoxy group (for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, fluoromethoxy, difluoromethoxy, trifluoro-methoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-difluoroethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (bb) an alkyl group(s) which may be substituted by a halogen atom(s) (for example, methyl, ethyl, propyl, isopropyl, butyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl and 1-(difluoromethyl)-2,2-difluoroethyl), or  
      (cc) a halogen atom(s),  
      (6) cyano group,  
      (7) carboxyl group,  
      (8) alkoxycarbonyl groups which may be substituted by a halogen atom(s) (for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, fluoromethoxycarbonyl, difluoromethoxycarbonyl, 2,2-difluoroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, methoxycarbonyl and ethoxycarbonyl),  
      (9) carbamoyl groups which may be substituted by an alkyl group(s) (for example, carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl and diethylcarbamoyl),  
      (10) alkylsulfonyl groups,  
      (11) C 1-3  alkylenedioxy groups,  
      (12) formyl group,  
      (13) optionally substituted phenyloxy groups (whose substituent(s) includes, for example, halogen atoms, alkyl groups and alkoxy groups),  
      (14) nitrogen-containing saturated heterocyclic groups (for example, pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl (whose nitrogen atoms may be substituted, for example, by methyl, ethyl or propyl)),  
      (15) cycloalkyloxy groups which may be substituted by a hydroxyl group, an oxo group, a carboxyl group, a carboxymethyl group, an alkoxycarbonyl group, an alkoxycarbonylalkyl group (e.g. methoxycarbonylmethyl, ethoxycarbonylmethyl or isopropoxycarbonylmethyl), an alkyl group, a fluoroalkyl group (e.g. fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl or perfluoroethyl), an alkoxyalkyl group (e.g. methoxymethyl, ethoxymethyl or isopropoxymethyl), a cycloalkyloxyalkyl group (e.g. cyclopropyloxymethyl, cyclopropyloxyethyl or cyclobutoxy), an alkoxy group, a cycloalkyloxy group or a halogen atom(s) (for example, 3-carboxycyclobutoxy, 3-methoxycarbonylcyclobutoxy, 3-ethoxycarbonylbutoxy, 2-methylcyclopropyloxy, 2-fluorocyclopropyloxy, 3-methoxycyclobutoxy, 3-fluorocyclobutoxy, 3,3-difluorocyclobutoxy and 3-(2-fluoroethyl)cyclobutoxy),  
      (16) alkoxy groups which may be substituted by a hydroxyl group, an oxo group, a carboxyl group, an alkoxycarbonyl group, a cycloalkyl group, an alkoxy group, a cycloalkyloxy group, an optionally substituted oxygen-containing heterocyclic group (e.g. a 5-or 6-membered saturated heterocyclic group having an oxygen atom(s), specific examples of which are tetrahydrofuranyl, tetrahydropyranyl, etc.; its substituent(s) includes, for example, halogen atoms, oxo group and alkoxy groups), or a halogen atom(s) (for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, 2-hydroxyethoxy, carboxymethoxy, methoxycarbonylmethoxy, ethoxycarbonylmethoxy, tert-butoxycarbonylmethoxy, cyclopropylmethoxy, cyclobutylmethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, isopropoxymethoxy, cyclopropyloxymethoxy, cyclobutoxymethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy and 1-(difluoromethyl)-2,2-difluoroethoxy),  
      (17) difluoromethylenedioxy,  
      (18) alkenyl groups which may be substituted by a halogen atom(s) (for example, vinyl, propenyl, methylpropenyl, butenyl and methylbutenyl),  
      (19) amino groups which may be substituted by an alkyl group(s) (for example, amino, methylamino, ethylamino, propylamino, dimethylamino, methylethylamino and diethylamino),  
      (20) optionally substituted alkylcarbonyl groups (whose substituent(s) includes, for example, halogen atoms, alkoxy groups and cycloalkyl groups),  
      (21) alkylcarbonyloxy groups (for example, methylcarbonyloxy, ethylcarbonyloxy and isopropylcarbonyloxy),  
      (22) cycloalkyl groups which may be substituted by a fluorine atom (for example, cyclopropyl, cyclobutyl, cyclopentyl, 2-fluorocyclopropyl, 2-fluorocyclobutyl, 3-fluorocyclobutylcyclobutyl, adamantyl and norbornyl),  
      (23) cycloalkylcarbonyl groups which may be substituted by a fluorine atom (for example, cyclopropylcarbonyl, 2-fluorocyclopropylcarbonyl, cyclobutylcarbonyl and cyclopentylcarbonyl),  
      (24) alkylthio groups,  
      (25) alkylsulfinyl groups,  
      (26) optionally substituted heteroaryl groups (whose substituent(s) includes, for example, halogen atoms, alkyl groups, alkoxy groups, haloalkyl groups and haloalkoxy groups),  
      (27) groups represented by the following formulas (T1) to (T16):  
                 
                 
 
 wherein R T  is absent or one or more R T s are present and are independently a halogen atom, a hydroxyl group, an oxo group, a carboxyl group, an optionally substituted alkyl group (whose substituent(s) includes, for example, halogen atoms and alkoxy groups), an optionally substituted alkoxycarbonyl group (whose substituent(s) includes, for example, halogen atoms and alkoxy groups), an optionally substituted alkoxy group (whose substituent(s) includes, for example, halogen atoms and alkoxy groups), an optionally substituted carbamoyl group (whose substituent(s) includes, for example, alkyl groups), or a saturated heterocyclic group oxycarbonyl group (the saturated heterocyclic group includes, for example, 5-or 6-membered saturated heterocyclic groups having one or two oxygen atoms, nitrogen atoms and/or sulfur atoms, specific examples of which are tetrahydrofuranyl, tetrahydropyranyl, dihydrofuranyl, tetrahydrothiopyranyl, tetrahydrodioxothiopyranyl, pyrrolidinyl, piperidyl, piperazyl, imidazolidinyl, oxazolidinyl, thiazolidinyl, etc.), or two R T s, when taken together, represent methylene, ethylene, trimethylene, tetramethylene or butenylene and may bind to one or more carbon atoms constituting the ring, to form a new ring; and R x  is a hydrogen atom or an alkyl group, and (28) aroyl groups. 
 
      The substituent(s) of each of the “optionally substituted heteroaryl group”, “optionally substituted aralkyl group”, “optionally substituted heteroarylalkyl group”, “optionally substituted aroyl group”, “optionally substituted heteroarylcarbonyl group”, “optionally substituted aryloxycarbonyl group”, “optionally substituted aryloxy group”, “optionally substituted aralkyloxy group”, “optionally substituted aralkyloxycarbonyl group”, “optionally substituted heteroaryloxy group”, “optionally substituted arylthio group”, “optionally substituted arylsulfinyl group” and “optionally substituted arylsulfonyl group” includes those exemplified as the substituent(s) of the above-mentioned “optionally substituted aryl group”.  
      The substituent(s) of the “optionally substituted alkylcarbonyl group” includes those exemplified as the substituents of (22) the “optionally substituted alkylcarbonyl groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of the “optionally substituted cycloalkylcarbonyl group” includes, for example, halogen atoms and alkoxy groups.  
      The substituent(s) of each of the “optionally substituted alkoxy group” and the “optionally substituted alkoxycarbonyl group” includes those exemplified as the substituents of (15) the “optionally substituted alkoxy groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of each of the “optionally substituted cycloalkyloxy group” and the “optionally substituted cycloalkyloxycarbonyl group” includes those exemplified as the substituents of (16) the “optionally substituted cycloalkyloxy groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of the “optionally substituted amino group” includes those exemplified as the substituents of (19) the “optionally substituted amino groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The substituent(s) of the “optionally substituted carbamoyl group” includes, for example,  
      (1) alkyl groups,  
      (2) cycloalkyl groups,  
      (3) aryl groups which may be substituted by the following (aa), (bb), (cc) or (dd):  
      (aa) a halogen atom(s),  
      (bb) an alkoxy group(s) which may be substituted by a halogen atom(s) (for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, perfluoroethoxy, 2-fluoro-1-(fluoromethyl)ethoxy and 1-(difluoromethyl)-2,2-difluoroethoxy),  
      (cc) an alkyl group(s) which may be substituted by a halogen atom(s) (for example, methyl, ethyl, propyl, isopropyl, butyl, methyl, ethyl, propyl, isopropyl, butyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2-fluoro-1-(fluoromethyl)ethyl and 1-(difluoromethyl)-2,2-difluoroethyl), or  
      (dd) a C 1-3  alkylenedioxy group,  
      (4) alkylsulfonyl groups,  
      (5) cycloalkylsulfonyl groups,  
      (6) optionally substituted arylsulfonyl groups (whose substituent(s) includes, for example, halogen atoms, alkyl groups, haloalkyl groups, alkoxy groups and haloalkoxy groups),  
      (7) alkylcarbonyl groups,  
      (8) alkoxycarbonyl groups,  
      and (9) optionally substituted aroyl groups (whose substituent(s) includes, for example, halogen atoms, alkyl groups, haloalkyl groups, alkoxy groups, haloalkoxy groups, alkoxycarbonyl groups and C 1-3  alkylenedioxy groups).  
      Specific examples of the “optionally substituted carbamoyl group” are carbamoyl, methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, diethylcarbamoyl, ethylmethylcarbamoyl, phenylcarbamoyl, phenylmethylcarbamoyl, etc.  
      The two substituents of the carbamoyl group may bind to each other to form an aliphatic heterocyclic ring which may contain carbon, nitrogen, oxygen or sulfur, such as pyrrolidine, piperidine, morpholine, thiomorpholine, thiomorpholine oxide, thiomorpholine dioxide, piperazine (whose nitrogen atom may be substituted, for example, by methyl, ethyl or propyl), or the like. Specific examples of such a carbamoyl group are pyrrolidinocarbamoyl, piperidinocarbamoyl, morpholinocarbamoyl, etc.  
      The substituent(s) of the “optionally substituted nitrogen-containing saturated heterocyclic group” includes, for example,  
      (1) halogen atoms,  
      (2) alkyl groups,  
      (3) alkyl groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, perfluoroethyl and methoxyethyl),  
      (4) alkoxy groups,  
      (5) alkoxy groups substituted by a halogen atom(s) or an alkoxy group (for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, methoxymethoxy, ethoxymethoxy, methoxyethoxy, ethoxyethoxy, methoxypropoxy and ethoxypropoxy),  
      (6) cyano group,  
      and (7) oxo group.  
      When two R 7 s or R 8 s are present, they may be present either on one and the same carbon atom or on different carbon atoms, respectively.  
      The phrase “two R 7 s or R 8 s, when taken together, represent methylene or ethylene and bind to one or more carbon atoms constituting the ring, to form a new ring” means that they form a spiro ring or a bicyclo ring through one and the same carbon atom or different carbon atoms.  
      The phrase “two R T s, when taken together, represent methylene, ethylene, trimethylene, tetramethylene or butenylene and bind to one or two carbon atoms constituting the ring, to form a new ring” means that they form a Spiro ring or a bicyclo ring through one and the same carbon atom or different carbon atoms.  
      The “haloalkoxy group” includes, for example, alkoxy groups of 1 to 4 carbon atoms substituted by a halogen atom(s). Specific examples thereof are fluoromethoxy, difluoromethoxy, trifluoromethoxy, etc.  
      The “haloalkyl group” includes, for example, alkyl groups of 1 to 4 carbon atoms substituted by a halogen atom(s). Specific examples thereof are fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, perfluoroethyl, etc.  
      The “C 1-3  alkylenedioxy group” includes, for example, methylenedioxy, ethylenedioxy and trimethylenedioxy.  
      The “substituted alkyl group” for R 19  includes, for example, alkyl groups of 1 to 3 carbon atoms substituted by a cycloalkyl group of 3 to 7 carbon atoms (for example, cyclopentyl, cyclohexyl or cycloheptyl) or an optionally substituted aryl group (for example, phenyl). Specific examples thereof are benzyl, p-chlorobenzyl, p-methoxybenzyl, p-fluorobenzyl, cyclopentylmethyl, cyclohexylmethyl, etc.  
      The “substituted alkenyl group” for R 19  includes, for example, alkenyl groups of 2 or 3 carbon atoms substituted by a cycloalkyl group of 5 to 7 carbon atoms (for example, cyclopentyl, cyclohexyl or cycloheptyl) or an aryl group (for example, phenyl). Examples thereof are vinyl, propenyl, allyl, isopropenyl and the like, which are substituted by phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or the like.  
      The “alkenyloxy group” for R 19  includes, for example, linear or branched alkenyloxy groups of 2 to 8 carbon atoms. Specific examples thereof are allyloxy, isobutenyloxy, etc.  
      The “substituted alkoxy group” for R 19  includes, for example, alkoxy groups of 1 to 3 carbon atoms substituted by a cycloalkyl group of 3 to 7 carbon atoms (for example, cyclopropyl, cyclopentyl, cyclohexyl or cycloheptyl) or an optionally substituted aryl group (for example, phenyl). Specific examples thereof are benzyloxy, phenethyloxy, cyclopropylmethyloxy, cyclopropylethyloxy, cyclopentylmethyloxy, etc.  
      The “substituted alkenyloxy group” for R 19  includes, for example, alkenyloxy groups of 2 or 3 carbon atoms substituted by a cycloalkyl group of 3 to 7 carbon atoms (for example, cyclopropyl, cyclopentyl, cyclohexyl or cycloheptyl) or an optionally substituted aryl group (for example, phenyl). Examples thereof are vinyloxy, propenyloxy, allyloxy and isopropenyloxy which are substituted by phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or the like.  
      Specific examples of the “optionally substituted aryloxy group” for R 19  are phenoxy, p-nitrophenoxy, p-methoxyphenoxy, p-fluorophenoxy, naphthoxy, etc.  
      Specific examples of each of the “substituted alkoxycarbonyl group” and the group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  (wherein R 18  and R 19  are as defined above) are pivaloyloxymethoxycarbonyl, 1-(cyclohexyloxycarbonyloxy)ethoxycarbonyl, 5-methyl-2-oxo-1,3-dioxolen-4-ylmethoxycarbonyl, acetoxymethyloxycarbonyl, propyloxymethoxycarbonyl, n-butoxymethoxycarbonyl, isobutoxymethoxycarbonyl, 1-(ethoxycarbonyloxy)ethoxycarbonyl, 1-(acetyloxy)ethoxycarbonyl, 1-(isobutoxy)ethoxycarbonyl, cyclohexylcarbonyloxymethoxycarbonyl, cyclopentylcarbonyloxymethoxycarbonyl, etc.  
      The substituent(s) of each of the “optionally substituted alkyl group” and the “optionally substituted alkoxy group” for Rc includes, for example, halogen atoms, alkoxy groups and cycloalkyl groups.  
      The substituent(s) of each of the “optionally substituted heteroaryl group” and the “optionally substituted heteroaryloxy group” for Rc includes those exemplified as the substituents of (7) the “optionally substituted heteroaryl groups” as the substituent(s) of the above-mentioned “optionally substituted alkyl group”.  
      The phrase “R 2 , R 3 , R 4  and R 5  may form an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring together with the adjacent carbon atoms” means that the formula (I):  
                 
 
 is shown as the formula (IV):  
                 
 
 wherein the ring A is an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring. The substituent of the ring A may be a carboxyl group or a group for obtaining a prodrug of a compound of the formula (IV) in which the substituent of the ring A is a carboxyl group. The substituent of the ring A may be one which is biologically or chemically convertible in a living body. 
 
      Specifically, the phrase “the ring A forms a benzene ring” means that the formula (IV) is shown as the formula (IVa):  
                 
 
      The substituent of the “optionally substituted benzene ring” portion as the ring A includes those exemplified as the substituent(s) of the “optionally substituted aryl group”, besides the above-mentioned groups represented by R 17 .  
      The cycloalkene ring in the case of the “optionally substituted cycloalkene ring” as the ring A includes, for example, cycloalkene rings of 4 to 10 carbon atoms. Specific examples thereof are cyclobutene, cyclopentene, cyclohexene, cycloheptene, norbornylene, etc.  
      Specifically, the phrase “the ring A forms a cycloalkene ring” means, for example, that the formula (IV) becomes, for instance, the formula (IVb):  
                 
 
 wherein i is an integer of 0 to 6. In addition, the aforesaid cycloalkene ring may contain an oxygen atom. Specific examples of such a compound are compounds of the formula (IVb-1):  
                 
 
 wherein each of j and k is an integer of 0 to 3, provided that when one of j and k is 0, the other is 2 or 3. 
 
      The substituent of the “optionally substituted cycloalkene ring” portion as the ring A includes, for example, alkyl groups, aralkyl groups, alkoxycarbonyl groups, alkoxy groups, oxo group and fluorine atom.  
      The 5-or 6-membered heteroaromatic ring in the case of the “optionally substituted 5-or 6-membered heteroaromatic ring” as the ring A includes, for example, 5-or 6-membered heteroaromatic rings containing, besides carbon atoms, one to three heteroatoms of one or two kinds selected from nitrogen atom, sulfur atom and oxygen atom. Specific examples thereof are thiophene, furan, pyrrole, imidazole, pyrazole, oxazole, pyridine, pyrazine, pyrimidine, pyridazine, thiazole, isothiazole, oxazole, isoxazole, etc.  
      Specifically, the phrase “the ring A forms a 5-or 6-membered heteroaromatic ring” means, for example, that the formula (IV) becomes, for instance, the formula (IVc-1), (IVc-2), (IVc-3), (IVc-4), (IVc-5), (IVc-6), (IVc-7), (IVc-8), (IVc-9), (IVc-10), (IVc-11) or (IVc-12):  
                 
                 
 
      The substituent of the “optionally substituted 5-or 6-membered heteroaromatic ring” portion as the ring A includes, for example, “optionally substituted alkoxycarbonyl groups” and groups of the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined above, besides the substituents exemplified as the substituent(s) of the “optionally substituted heteroaryl group”.  
      When R 3  and R 5  are taken together to form a double bond on the ring, the formula (I) preferably represents the formula (II):  
                 
 
 wherein R 4  is as defined in [1]; R 15  and R 16  are as defined in [12]; R 1a  is a hydrogen atom, methyl or the formula: —Ra—Rb-Rc wherein Ra, Rb and Rc are as defined in [14]; and R 2a  is a cyano group, a carboxyl group, an oxazolyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted cycloalkyloxycarbonyl group, a tetrahydro-furanyloxycarbonyl group, an optionally substituted aryloxycarbonyl group, a cinnamyloxycarbonyl group, or a group represented by the formula: —C(O)OCH(R 18 )OC(O)R 19  wherein R 18  and R 19  are as defined in [1]. More preferably, the formula (I) represents the formula (III):  
                 
 
 wherein R 16  is as defined in [12]; R 1a  and R 2a  are as defined in [16]; and R 15a  is a chlorine atom, a bromine atom, an iodine atom, a cyano group, methyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy or trifluoromethoxy. 
 
      As the “prodrug”, there are exemplified those which are easily hydrolyzed in a living body to regenerate the compound (I) of the present invention. Specific examples thereof are compounds obtained by converting the amino group of a compound represented by the formula (I) to —NHQX. Here, the following are exemplified as Q x :  
                 
 
 (2) —COR 21  
 
 (3) —COO—CR 22 (R 23 )—OCOR 24  
 
 (4) —COOR 25  
 
 wherein R 21  is a hydrogen atom, an alkyl group or an optionally substituted aryl group; R 22  and R 23  are independently a hydrogen atom or an alkyl group; R 24  is a hydrogen atom, an alkyl group, an aryl group or a benzyl group; and R 25  is an alkyl group or a benzyl group. 
 
      Preferable examples of Q x  are the group of (1) and the groups of (3). Preferable examples of the groups of (3) are groups in which R 22  is a hydrogen atom, R 23  is a hydrogen atom, methyl or ethyl and R 24  is methyl or ethyl. These compounds may be produced according to conventional processes (for example, J. Med. Chem. 35, 4727 (1992) and WO 01/40180). In addition, the prodrug may be one which is converted to the original compound under physiological conditions, such as those described in “Development of Medicines Vol. 7, Molecular Design”, pp. 163-198, Hirokawa Shoten, 1990.  
      As the “pharmaceutically acceptable salt”, there are exemplified inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, etc., and organic acid salts such as acetate, propionate, oxalate, succinate, lactate, malate, tartrate, citrate, maleate, fumarate, methanesulfonate, benzenesulfonate, p-toluenesulfonate, ascorbate, etc.  
      In addition, the present invention includes compounds represented by the formula (I), prodrugs thereof and pharmaceutically acceptable salts of the compounds or prodrugs. The present invention also includes their hydrates or solvates (e.g. ethanol solvate). Furthermore, the present invention includes all tautomers, all existing stereoisomers and all crystal forms of the compound (I) of the present invention.  
      Preferable examples of the compound of the present invention are the following compounds. In the compounds listed in the following tables, the following abbreviations are used in some cases for the simplification of description.  
      2-Py: 2-pyridyl group, 3-Py: 3-pyridyl group, 4-Py: 4-pyridyl group, Ph: phenyl group, Et: ethyl group, Me: methyl group, n-Pr: n-propyl group, i-Pr: isopropyl group, n-Bu: n-butyl group, t-Bu: tert-butyl group, Bn: benzyl group, Ac: acetyl group, cycpro: cyclopropyl group, cycbu: cyclobutyl group, cychex: cyclohexyl group, etoet: ethoxyethyl group, meoet: methoxyethyl group, f2etoet: 2,2-difluoroethoxyethyl group, f2meoet: difluoromethoxyethyl group, cycprooet: cyclopropyloxyethyl group, isoproet: isopropyloxyethyl group, ms: methanesulfonyl group, etomet: ethoxymethyl group, meomet: methoxymethyl group, f2meomet: difluoromethoxymethyl group, f2etomet: 2,2-difluoroethoxymethyl group.  
      In addition, the following abbreviations of partial structures are used in some cases.  
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
 
                                                                                                  No.   R 6     Y-NH 2     R 2     R 4                                           1   Q3   Q1   H   Me       2   Q4   Q2   H   H       3   Q5   Q1   H   Me       4   Q13   Q1   H   Me       5   Q6   Q1   H   Me       6   Q7   Q1   H   H       7   Q8   Q1   H   H       8   Q9   Q1   H   H       9   Q10   Q1   H   H       10   Q11   Q1   H   H       11   Q12   Q1   H   H       12   Q5   Q1   Me   H       13   Q13   Q1   Me   H       14   Q5   Q1   H   Me       15   Q13   Q1   H   Me       16   Q5   Q1   Me   Me       17   Q13   Q1   Me   Et       18   Q13   Q1   CF 3     H       19   Q4   Q1   CF 3     H       20   Q5   Q1   Me   CF 3         21   Q13   Q1   H   CF 3         22   Q8   Q1   CF 3     H       23   Q8   Q1   CN   H       24   Q8   Q1   Ac   H       25   Q5   Q1   Et   H       26   Q13   Q1   Et   H       27   Q13   Q1   Et   H       28   Q5   Q1   i-Pr   H       29   Q13   Q1   cycpro   H       30   Q8   Q1   cycpro   H       31   Q5   Q1   MeO(Me) 2 C   H       32   Q8   Q1   MeO(Me) 2 C   H       33   Q4   Q1   MeO(Me) 2 C   H       34   Q8   Q1   meomet   H       35   Q13   Q1   meomet   H       36   Q4   Q1   meomet   H       37   Q5   Q1   MsNHCH 2     H       38   Q8   Q1   MsNHCH 3     H       39   Q13   Q1   MsC(Me) 2     H       40   Q13   Q1   Q117   H       41   Q8   Q1   Q133   H       42   Q5   Q1   Q133   H       43   Q8   Q1   Q155   H       44   Q4   Q1   Q155   H                  
 
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No. 
                 R 6   
                 R 2   
               
               
                   
               
            
           
           
               
               
               
            
               
                 45 
                 Q8 
                 Q167 
               
               
                 46 
                 Q13 
                 Q154 
               
               
                 47 
                 Q4 
                 A167 
               
               
                 48 
                 Q13 
                 CN 
               
               
                 49 
                 Q4 
                 CO 2 H 
               
               
                 50 
                 Q4 
                 Q134 
               
               
                 51 
                 Q13 
                 Q131 
               
               
                 52 
                 Q13 
                 Q132 
               
               
                 53 
                 Q8 
                 MsC(Me) 2   
               
               
                 54 
                 Q13 
                 Q14 
               
               
                 55 
                 Q8 
                 Q14 
               
               
                 56 
                 Q4 
                 Bn 
               
               
                 57 
                 Q13 
                 Q15 
               
               
                 58 
                 Q5 
                 Q16 
               
               
                 59 
                 Q13 
                 Q16 
               
               
                 60 
                 Q5 
                 Q17 
               
               
                 61 
                 Q13 
                 Q18 
               
               
                 62 
                 Q5 
                 Q19 
               
               
                 63 
                 Q13 
                 Q19 
               
               
                 64 
                 Q5 
                 Q20 
               
               
                 65 
                 Q13 
                 Q21 
               
               
                 66 
                 Q5 
                 2-Py 
               
               
                 67 
                 Q13 
                 3-Py 
               
               
                 68 
                 Q5 
                 4-Py 
               
               
                 69 
                 Q13 
                 Q25 
               
               
                 70 
                 Q5 
                 Q26 
               
               
                 71 
                 Q13 
                 Q27 
               
               
                 72 
                 Q5 
                 Q3 
               
               
                 73 
                 Q13 
                 Q28 
               
               
                 74 
                 Q5 
                 Q29 
               
               
                 75 
                 Q13 
                 Q30 
               
               
                 76 
                 Q5 
                 Q6 
               
               
                 77 
                 Q13 
                 Q31 
               
               
                 78 
                 Q13 
                 Q32 
               
               
                 79 
                 Q5 
                 Q33 
               
               
                 80 
                 Q13 
                 Q34 
               
               
                 81 
                 Q13 
                 Q35 
               
               
                 82 
                 Q5 
                 Q36 
               
               
                 83 
                 Q13 
                 Q37 
               
               
                 84 
                 Q9 
                 Q38 
               
               
                 85 
                 Q5 
                 Q39 
               
               
                 86 
                 Q13 
                 Q67 
               
               
                 87 
                 Q8 
                 Q40 
               
               
                 88 
                 Q5 
                 Q41 
               
               
                 89 
                 Q8 
                 Q42 
               
               
                 90 
                 Q4 
                 Q43 
               
               
                 91 
                 Q5 
                 Q44 
               
               
                 92 
                 Q13 
                 Ph 
               
               
                 93 
                 Q4 
                 2-Py 
               
               
                 94 
                 Q5 
                 3-Py 
               
               
                 95 
                 Q5 
                 Q45 
               
               
                 96 
                 Q5 
                 Q46 
               
               
                 97 
                 Q13 
                 Q26 
               
               
                 98 
                 Q8 
                 Q27 
               
               
                 99 
                 Q4 
                 Q3 
               
               
                 100 
                 Q5 
                 Q28 
               
               
                 101 
                 Q13 
                 Q29 
               
               
                 102 
                 Q4 
                 Q30 
               
               
                 103 
                 Q5 
                 Q47 
               
               
                 104 
                 Q13 
                 Q48 
               
               
                 105 
                 Q5 
                 Q32 
               
               
                 106 
                 Q13 
                 Q49 
               
               
                 107 
                 Q4 
                 Q50 
               
               
                 108 
                 Q5 
                 Q51 
               
               
                 109 
                 Q13 
                 Q52 
               
               
                 110 
                 Q4 
                 Q53 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 No. 
                 R 1   
                 R 6   
                 R 2   
                 Y-NH 2   
               
               
                   
               
               
                 111 
                 Me 
                 Q5 
                 Q55 
                 Q1 
               
               
                 112 
                 Me 
                 Q13 
                 Q55 
                 Q1 
               
               
                 113 
                 Me 
                 Q4 
                 Q56 
                 Q1 
               
               
                 114 
                 Me 
                 Q5 
                 Q22 
                 Q1 
               
               
                 115 
                 Me 
                 Q13 
                 Q23 
                 Q1 
               
               
                 116 
                 Me 
                 Q4 
                 Q24 
                 Q1 
               
               
                 117 
                 Me 
                 Q5 
                 Q57 
                 Q1 
               
               
                 118 
                 Me 
                 Q13 
                 Q58 
                 Q1 
               
               
                 119 
                 Me 
                 Q4 
                 Q59 
                 Q1 
               
               
                 120 
                 Me 
                 Q5 
                 Q60 
                 Q1 
               
               
                 121 
                 Me 
                 Q13 
                 Q61 
                 Q1 
               
               
                 122 
                 Me 
                 Q4 
                 Q62 
                 Q1 
               
               
                 123 
                 Me 
                 Q5 
                 Q63 
                 Q1 
               
               
                 124 
                 Me 
                 Q13 
                 Q15 
                 Q1 
               
               
                 125 
                 Me 
                 Q4 
                 Q64 
                 Q1 
               
               
                 126 
                 Me 
                 Q5 
                 Q65 
                 Q1 
               
               
                 127 
                 Me 
                 Q13 
                 Q66 
                 Q1 
               
               
                 128 
                 Me 
                 Q4 
                 Q70 
                 Q1 
               
               
                 129 
                 Me 
                 Q5 
                 Q68 
                 Q1 
               
               
                 130 
                 Me 
                 Q13 
                 Q69 
                 Q1 
               
               
                 131 
                 Q70 
                 Q5 
                 CN 
                 Q1 
               
               
                 132 
                 Q71 
                 Q13 
                 Me 
                 Q1 
               
               
                 133 
                 Q72 
                 Q8 
                 CF 3   
                 Q1 
               
               
                 134 
                 Q73 
                 Q5 
                 Ac 
                 Q1 
               
               
                 135 
                 Q74 
                 Q13 
                 CN 
                 Q1 
               
               
                 136 
                 Q75 
                 Q4 
                 CF 3   
                 Q1 
               
               
                 137 
                 Q76 
                 Q5 
                 H 
                 Q1 
               
               
                 138 
                 Q77 
                 Q13 
                 Me 
                 Q1 
               
               
                 139 
                 Q78 
                 Q13 
                 CN 
                 Q1 
               
               
                 140 
                 Q79 
                 Q5 
                 Ac 
                 Q1 
               
               
                 141 
                 Q80 
                 Q13 
                 CN 
                 Q1 
               
               
                 142 
                 Q81 
                 Q4 
                 CF 3   
                 Q1 
               
               
                 143 
                 Q82 
                 Q8 
                 H 
                 Q1 
               
               
                 144 
                 Q83 
                 Q13 
                 Me 
                 Q1 
               
               
                 145 
                 Q84 
                 Q4 
                 CF 3   
                 Q1 
               
               
                 146 
                 Q85 
                 Q5 
                 Ac 
                 Q1 
               
               
                 147 
                 Q86 
                 Q13 
                 CN 
                 Q1 
               
               
                 148 
                 Q78 
                 Me 
                 CN 
                 Q1 
               
               
                 149 
                 Q79 
                 Q5 
                 H 
                 Q1 
               
               
                 150 
                 Q87 
                 Q13 
                 Me 
                 Q1 
               
               
                 151 
                 Q88 
                 Q4 
                 Me 
                 Q1 
               
               
                 152 
                 Q89 
                 Q5 
                 Ac 
                 Q1 
               
               
                 153 
                 Q90 
                 Q13 
                 CN 
                 Q1 
               
               
                 154 
                 Q91 
                 Q8 
                 CF 3   
                 Q1 
               
               
                 155 
                 Q92 
                 Q5 
                 CN 
                 Q1 
               
               
                 156 
                 Q93 
                 Q13 
                 CF 3   
                 Q1 
               
               
                 157 
                 Me 
                 Q5 
                 H 
                 Q94 
               
               
                 158 
                 Me 
                 Q13 
                 Me 
                 Q94 
               
               
                 159 
                 Me 
                 Q4 
                 Et 
                 Q94 
               
               
                 160 
                 Me 
                 Q5 
                 Ac 
                 Q94 
               
               
                 161 
                 Me 
                 Q13 
                 CN 
                 Q94 
               
               
                 162 
                 Me 
                 Q4 
                 Me 
                 Q94 
               
               
                 163 
                 Me 
                 Q5 
                 H 
                 Q95 
               
               
                 164 
                 Me 
                 Q13 
                 CN 
                 Q95 
               
               
                 165 
                 Me 
                 Q4 
                 Et 
                 Q96 
               
               
                 166 
                 Me 
                 Q5 
                 Ac 
                 A97 
               
               
                 167 
                 Me 
                 Q13 
                 CN 
                 Q98 
               
               
                 168 
                 Me 
                 Q4 
                 CF 3   
                 Q97 
               
               
                 169 
                 Me 
                 Q5 
                 H 
                 Q99 
               
               
                 170 
                 Me 
                 Q13 
                 Me 
                 Q100 
               
               
                 171 
                 Me 
                 Q4 
                 Et 
                 Q101 
               
               
                 172 
                 Me 
                 Q5 
                 Ac 
                 Q102 
               
               
                 173 
                 Me 
                 Q13 
                 CN 
                 Q103 
               
               
                 174 
                 Me 
                 Q4 
                 CF 3   
                 Q103 
               
               
                 175 
                 Me 
                 Q5 
                 H 
                 Q103 
               
               
                 176 
                 Me 
                 Q13 
                 Me 
                 Q103 
               
               
                 177 
                 Me 
                 Q4 
                 Me 
                 Q104 
               
               
                 178 
                 Me 
                 Q5 
                 Ac 
                 Q105 
               
               
                 179 
                 Me 
                 Q13 
                 CN 
                 Q106 
               
               
                 180 
                 Me 
                 Q4 
                 CF 3   
                 Q107 
               
               
                 181 
                 Me 
                 Q5 
                 CN 
                 Q98 
               
               
                 182 
                 Me 
                 Q13 
                 CF 3   
                 Q108 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 No. 
                 R 1   
                 R 6   
                 R 2   
                 R 4   
               
               
                   
               
               
                 183 
                 H 
                 Q5 
                 Q117 
                 Me 
               
               
                 184 
                 Me 
                 Q13 
                 Q117 
                 Me 
               
               
                 185 
                 H 
                 Q4 
                 Q133 
                 Me 
               
               
                 186 
                 Me 
                 Q13 
                 Q133 
                 Me 
               
               
                 187 
                 H 
                 Q5 
                 Q133 
                 Me 
               
               
                 188 
                 H 
                 Q13 
                 Q134 
                 Me 
               
               
                 189 
                 H 
                 Q5 
                 Q135 
                 Me 
               
               
                 190 
                 H 
                 Q13 
                 Q135 
                 Me 
               
               
                 191 
                 Q79 
                 Q5 
                 Q133 
                 Me 
               
               
                 192 
                 Q71 
                 Q13 
                 Q117 
                 Me 
               
               
                 193 
                 Q80 
                 Q5 
                 Q133 
                 Me 
               
               
                 194 
                 Q81 
                 Q13 
                 Q117 
                 Me 
               
               
                 195 
                 Q89 
                 Q5 
                 Q133 
                 Me 
               
               
                 196 
                 Q87 
                 Q5 
                 Q135 
                 Me 
               
               
                 197 
                 Q78 
                 Q13 
                 Q117 
                 Me 
               
               
                 198 
                 Q85 
                 Q5 
                 Q133 
                 Me 
               
               
                 199 
                 Q86 
                 Q13 
                 Q117 
                 Me 
               
               
                 200 
                 Q78 
                 Q5 
                 Q135 
                 Me 
               
               
                 201 
                 Q72 
                 Q13 
                 Q133 
                 Me 
               
               
                 202 
                 Q73 
                 Q5 
                 Q117 
                 Me 
               
               
                 203 
                 Q74 
                 Q4 
                 Q135 
                 Me 
               
               
                 204 
                 Q75 
                 Q5 
                 Q117 
                 Me 
               
               
                 205 
                 Q90 
                 Q13 
                 Q135 
                 Me 
               
               
                 206 
                 Q91 
                 Q5 
                 Q117 
                 Me 
               
               
                 207 
                 Q76 
                 Q5 
                 Q133 
                 Me 
               
               
                 208 
                 Q79 
                 Q13 
                 Q135 
                 Me 
               
               
                 209 
                 Me 
                 Q5 
                 Q109 
                 H 
               
               
                 210 
                 Me 
                 Q5 
                 Q110 
                 H 
               
               
                 211 
                 Me 
                 Q5 
                 Q111 
                 H 
               
               
                 212 
                 Q136 
                 Q5 
                 CF 3   
                 H 
               
               
                 213 
                 Q137 
                 Q5 
                 Ac 
                 H 
               
               
                 214 
                 Q138 
                 Q5 
                 H 
                 H 
               
               
                 215 
                 Q138 
                 Q5 
                 Me 
                 H 
               
               
                 216 
                 Q139 
                 Q5 
                 CN 
                 H 
               
               
                 217 
                 Q140 
                 Q5 
                 CN 
                 H 
               
               
                 218 
                 Q141 
                 Q5 
                 CN 
                 H 
               
               
                 219 
                 Q142 
                 Q5 
                 CN 
                 H 
               
               
                 220 
                 Q143 
                 Q5 
                 CN 
                 H 
               
               
                 221 
                 Q144 
                 Q5 
                 Q58 
                 H 
               
               
                 222 
                 Q136 
                 Q5 
                 Q5 
                 H 
               
               
                 223 
                 Q136 
                 Q5 
                 Q12 
                 Me 
               
               
                 224 
                 Q136 
                 Q5 
                 Q11 
                 H 
               
               
                 225 
                 Q136 
                 Q5 
                 Ph 
                 Me 
               
               
                 226 
                 Q137 
                 Q5 
                 Ph 
                 H 
               
               
                 227 
                 Me 
                 Q5 
                 PhO 
                 H 
               
               
                 228 
                 Q136 
                 Q5 
                 PhO 
                 H 
               
               
                 229 
                 Me 
                 Q5 
                 PhO 
                 Me 
               
               
                 230 
                 Q136 
                 Q5 
                 PhS 
                 H 
               
               
                 231 
                 Me 
                 Q5 
                 Q168 
                 H 
               
               
                 232 
                 Q136 
                 Q5 
                 Q168 
                 H 
               
               
                 233 
                 Q143 
                 Q5 
                 Ac 
                 H 
               
               
                 234 
                 Q137 
                 Q5 
                 Ac 
                 Me 
               
               
                 235 
                 Q144 
                 Q5 
                 Ph 
                 H 
               
               
                 236 
                 Q144 
                 Q5 
                 CN 
                 H 
               
               
                 237 
                 Q145 
                 Q5 
                 CN 
                 H 
               
               
                 238 
                 Q144 
                 Q5 
                 CF 3   
                 H 
               
               
                 239 
                 Q144 
                 Q5 
                 Ac 
                 H 
               
               
                 240 
                 Q144 
                 Q5 
                 CN 
                 Me 
               
               
                 241 
                 Q146 
                 Q5 
                 CN 
                 H 
               
               
                 242 
                 Q136 
                 Q5 
                 Q15 
                 H 
               
               
                 243 
                 Q147 
                 Q5 
                 Ph 
                 H 
               
               
                 244 
                 Q138 
                 Q5 
                 Ph 
                 H 
               
               
                 245 
                 Me 
                 Q5 
                 Q45 
                 H 
               
               
                 246 
                 Me 
                 Q5 
                 Q113 
                 H 
               
               
                 247 
                 Me 
                 Q5 
                 Q114 
                 H 
               
               
                 248 
                 Q136 
                 Q5 
                 Q117 
                 Me 
               
               
                 249 
                 Q148 
                 Q5 
                 Q117 
                 Me 
               
               
                 250 
                 Q149 
                 Q5 
                 Q113 
                 Me 
               
               
                 251 
                 Q136 
                 Q5 
                 Q150 
                 Me 
               
               
                 252 
                 Q136 
                 Q5 
                 Q135 
                 Me 
               
               
                 253 
                 Q136 
                 Q5 
                 Q134 
                 Me 
               
               
                 254 
                 Q150 
                 Q5 
                 Q117 
                 Me 
               
               
                 255 
                 Q136 
                 Q5 
                 Q154 
                 H 
               
               
                 256 
                 Q136 
                 Q5 
                 Q155 
                 H 
               
               
                 257 
                 H 
                 Q5 
                 Q153 
                 Me 
               
               
                 258 
                 Q115 
                 Q5 
                 CN 
                 H 
               
               
                 259 
                 Q151 
                 Q5 
                 CN 
                 H 
               
               
                 260 
                 Q152 
                 Q5 
                 CN 
                 Me 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 R 1   
                 R 2   
                 R 4   
                 R 15   
                 R 16   
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 261 
                 Q156 
                 Ph 
                 H 
                 Me 
                 H 
               
               
                 262 
                 Q157 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 263 
                 Q158 
                 CN 
                 H 
                 Me 
                 F 
               
               
                 264 
                 Q159 
                 CN 
                 H 
                 Cl 
                 F 
               
               
                 265 
                 Q160 
                 Ac 
                 H 
                 Me 
                 H 
               
               
                 266 
                 Q161 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 267 
                 Q162 
                 Ph 
                 H 
                 Me 
                 F 
               
               
                 268 
                 Q162 
                 CN 
                 H 
                 Cl 
                 F 
               
               
                 269 
                 Q162 
                 CN 
                 H 
                 Me 
                 H 
               
               
                 270 
                 Q160 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 271 
                 Q161 
                 CN 
                 H 
                 Me 
                 F 
               
               
                 272 
                 H 
                 Q156 
                 Me 
                 Cl 
                 F 
               
               
                 273 
                 H 
                 Q157 
                 Me 
                 Me 
                 H 
               
               
                 274 
                 Me 
                 Q158 
                 Me 
                 Me 
                 H 
               
               
                 275 
                 Me 
                 Q159 
                 Me 
                 Cl 
                 H 
               
               
                 276 
                 Me 
                 Q161 
                 Me 
                 Me 
                 F 
               
               
                 277 
                 Me 
                 Q162 
                 Me 
                 Cl 
                 F 
               
               
                 278 
                 Q143 
                 Q117 
                 Me 
                 Me 
                 H 
               
               
                 279 
                 Q165 
                 Q117 
                 Me 
                 Cl 
                 H 
               
               
                 280 
                 Q143 
                 Q133 
                 Me 
                 Me 
                 F 
               
               
                 281 
                 Q166 
                 Q117 
                 Me 
                 Cl 
                 F 
               
               
                 282 
                 Q143 
                 Ph 
                 Me 
                 Me 
                 H 
               
               
                 283 
                 Q165 
                 Et 
                 Me 
                 Cl 
                 H 
               
               
                 284 
                 Q136 
                 CN 
                 Me 
                 Me 
                 F 
               
               
                 285 
                 Q166 
                 CF 3   
                 H 
                 Cl 
                 F 
               
               
                 286 
                 Q143 
                 Ac 
                 H 
                 Me 
                 H 
               
               
                 287 
                 Me 
                 Ph 
                 Me 
                 Me 
                 H 
               
               
                 288 
                 Me 
                 Me 
                 Me 
                 Cl 
                 F 
               
               
                 289 
                 Me 
                 CN 
                 Me 
                 Me 
                 F 
               
               
                 290 
                 Me 
                 CF 3   
                 Me 
                 Cl 
                 H 
               
               
                 291 
                 Me 
                 Ac 
                 Me 
                 Me 
                 H 
               
               
                 292 
                 Me 
                 H 
                 Me 
                 Cl 
                 F 
               
               
                 293 
                 Me 
                 PhO 
                 Me 
                 Me 
                 H 
               
               
                 294 
                 Me 
                 PhO 
                 Me 
                 Cl 
                 H 
               
               
                 295 
                 Me 
                 PhO 
                 Me 
                 Cl 
                 F 
               
               
                 296 
                 Me 
                 Q117 
                 Me 
                 Cl 
                 F 
               
               
                 297 
                 Me 
                 Q133 
                 Me 
                 Me 
                 F 
               
               
                 298 
                 Me 
                 Q135 
                 Me 
                 Cl 
                 H 
               
               
                 299 
                 Me 
                 CN 
                 Me 
                 Me 
                 H 
               
               
                 300 
                 Me 
                 Q15 
                 Me 
                 Me 
                 H 
               
               
                 301 
                 Me 
                 Q116 
                 Me 
                 Cl 
                 F 
               
               
                 302 
                 Me 
                 Ph 
                 Me 
                 Me 
                 F 
               
               
                 303 
                 Me 
                 Q26 
                 Me 
                 Cl 
                 H 
               
               
                 304 
                 Me 
                 Q25 
                 Me 
                 Me 
                 H 
               
               
                 305 
                 Me 
                 Q26 
                 Me 
                 Cl 
                 H 
               
               
                 306 
                 Me 
                 Q111 
                 Me 
                 Me 
                 H 
               
               
                 307 
                 Me 
                 Q118 
                 Me 
                 Cl 
                 H 
               
               
                 308 
                 Me 
                 Q57 
                 Me 
                 Me 
                 H 
               
               
                 309 
                 Me 
                 Q119 
                 Me 
                 Cl 
                 H 
               
               
                 310 
                 Me 
                 Q120 
                 Me 
                 Me 
                 F 
               
               
                 311 
                 Me 
                 Q121 
                 Me 
                 Cl 
                 H 
               
               
                 312 
                 Me 
                 Q122 
                 Me 
                 Cl 
                 F 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 No. 
                 R 1   
                 R 2   
                 R 4   
                 R 15   
                 R 16   
               
               
                   
               
               
                 313 
                 Me 
                 Q123 
                 H 
                 Me 
                 H 
               
               
                 314 
                 Me 
                 Q124 
                 H 
                 Cl 
                 H 
               
               
                 315 
                 Me 
                 Q125 
                 H 
                 Me 
                 H 
               
               
                 316 
                 Q79 
                 Q126 
                 H 
                 Cl 
                 H 
               
               
                 317 
                 Q118 
                 Ac 
                 H 
                 Me 
                 H 
               
               
                 318 
                 Q127 
                 Ac 
                 H 
                 Cl 
                 H 
               
               
                 319 
                 Q118 
                 CN 
                 H 
                 Me 
                 H 
               
               
                 320 
                 Q127 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 321 
                 Me 
                 Q128 
                 H 
                 Me 
                 H 
               
               
                 322 
                 Me 
                 Q136 
                 H 
                 Cl 
                 H 
               
               
                 323 
                 Me 
                 Q137 
                 H 
                 Me 
                 H 
               
               
                 324 
                 Q79 
                 Q136 
                 H 
                 Cl 
                 H 
               
               
                 325 
                 Q130 
                 Q136 
                 H 
                 Me 
                 H 
               
               
                 326 
                 Q26 
                 CN 
                 H 
                 Me 
                 H 
               
               
                 327 
                 Q53 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 328 
                 Q26 
                 Ac 
                 H 
                 Me 
                 H 
               
               
                 329 
                 Q121 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 330 
                 Q26 
                 Ac 
                 Me 
                 Me 
                 H 
               
               
                 331 
                 Q129 
                 CN 
                 H 
                 Cl 
                 H 
               
               
                 332 
                 3-Py 
                 CN 
                 Me 
                 Me 
                 H 
               
               
                 333 
                 Q79 
                 H 
                 Q136 
                 Cl 
                 H 
               
               
                 334 
                 H 
                 H 
                 Q136 
                 Me 
                 H 
               
               
                 335 
                 Me 
                 H 
                 Q136 
                 Cl 
                 H 
               
               
                 336 
                 Me 
                 CN 
                 Q136 
                 Me 
                 H 
               
               
                 337 
                 Q79 
                 Ac 
                 Q136 
                 Cl 
                 H 
               
               
                 338 
                 Q79 
                 CN 
                 Q136 
                 Me 
                 H 
               
               
                 339 
                 Me 
                 Q169 
                 H 
                 Me 
                 H 
               
               
                 340 
                 Me 
                 Q170 
                 H 
                 Cl 
                 F 
               
               
                 341 
                 Me 
                 Q171 
                 Me 
                 Me 
                 F 
               
               
                 342 
                 Me 
                 Q172 
                 Me 
                 Cl 
                 H 
               
               
                 343 
                 Me 
                 Q172 
                 Me 
                 Cl 
                 F 
               
               
                 344 
                 Me 
                 Q172 
                 Q173 
                 Cl 
                 F 
               
               
                 345 
                 Me 
                 Q172 
                 f2etoet 
                 Cl 
                 F 
               
               
                 346 
                 Me 
                 Q172 
                 f2Meoet 
                 Cl 
                 F 
               
               
                 347 
                 Me 
                 Q172 
                 etoet 
                 Cl 
                 F 
               
               
                 348 
                 Me 
                 Q172 
                 Q137 
                 Cl 
                 F 
               
               
                 349 
                 Me 
                 Q172 
                 isopret 
                 Me 
                 F 
               
               
                 350 
                 H 
                 Q172 
                 H 
                 Cl 
                 H 
               
               
                 351 
                 Me 
                 CN 
                 Me 
                 Me 
                 H 
               
               
                 352 
                 Me 
                 Q15 
                 Me 
                 Me 
                 H 
               
               
                 353 
                 Me 
                 Q116 
                 Me 
                 Cl 
                 F 
               
               
                 354 
                 Me 
                 Ph 
                 Me 
                 Me 
                 F 
               
               
                 355 
                 Me 
                 Q26 
                 Me 
                 Cl 
                 H 
               
               
                 356 
                 Me 
                 Q25 
                 Me 
                 Me 
                 H 
               
               
                 357 
                 Me 
                 Q26 
                 Me 
                 Cl 
                 H 
               
               
                 358 
                 Me 
                 Q111 
                 Me 
                 Me 
                 H 
               
               
                 359 
                 Me 
                 Q118 
                 Me 
                 Cl 
                 H 
               
               
                 360 
                 Me 
                 Q57 
                 Me 
                 Me 
                 H 
               
               
                 361 
                 Me 
                 Q119 
                 Me 
                 Cl 
                 H 
               
               
                 362 
                 Me 
                 Q120 
                 Me 
                 Me 
                 F 
               
               
                 363 
                 Me 
                 Q121 
                 Me 
                 Cl 
                 H 
               
               
                 364 
                 Me 
                 Q122 
                 Me 
                 Cl 
                 F 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 No. 
                 R 17   
                 R 15   
                 R 16   
               
               
                   
               
               
                 365 
                 6-OMe 
                 Cl 
                 H 
               
               
                 366 
                 8-Cl 
                 Me 
                 H 
               
               
                 367 
                 6-Q117 
                 Cl 
                 H 
               
               
                 368 
                 6-CN 
                 Cl 
                 F 
               
               
                 369 
                 7-Q117 
                 Cl 
                 H 
               
               
                 370 
                 6-Me 
                 Cl 
                 H 
               
               
                 371 
                 8-Q117 
                 Cl 
                 H 
               
               
                 372 
                 7-OEt 
                 Cl 
                 H 
               
               
                 373 
                 6-Me/8-CN 
                 Me 
                 H 
               
               
                 374 
                 8-Me/7-OMe 
                 Cl 
                 H 
               
               
                 375 
                 6-Ac 
                 Cl 
                 H 
               
               
                 376 
                 6-Q117/8-F 
                 Cl 
                 H 
               
               
                 377 
                 9-Q117 
                 Cl 
                 H 
               
               
                 378 
                 6-OPh 
                 Cl 
                 H 
               
               
                 379 
                 9-OMe 
                 Cl 
                 H 
               
               
                 380 
                 7-CN/8-F 
                 Cl 
                 F 
               
               
                 381 
                 9-CN/8-F 
                 Cl 
                 H 
               
               
                 382 
                 7-CN/9-F 
                 Cl 
                 H 
               
               
                 383 
                 7-CN/8-OMe 
                 Cl 
                 H 
               
               
                 384 
                 9-CN/8-OMe 
                 Cl 
                 F 
               
               
                 385 
                 7-CN/8-meoet 
                 Cl 
                 H 
               
               
                 386 
                 7-CN/8-f2etoet 
                 Cl 
                 F 
               
               
                 387 
                 9-CN/7-OMe 
                 Cl 
                 H 
               
               
                 388 
                 9-CN/7-meomet 
                 Cl 
                 F 
               
               
                 389 
                 9-CN/8-meomet 
                 Cl 
                 H 
               
               
                 390 
                 7-CN/8-O(i-Pr) 
                 Cl 
                 F 
               
               
                   
               
            
           
           
               
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17   
               
               
                   
               
               
                 391 
                 7-CN/8-Q137 
               
               
                 392 
                 7-CN/8-Q140 
               
               
                 393 
                 7-CN/8-Q138 
               
               
                 394 
                 7-CN/8-Q143 
               
               
                 395 
                 7-CN/8-Q115 
               
               
                 396 
                 7-CN/8-Q151 
               
               
                 397 
                 7-Q115/8-CN 
               
               
                 398 
                 7-Q151/8-CN 
               
               
                 399 
                 7-Q138/8-CN 
               
               
                 400 
                 7-Q140/8-CN 
               
               
                 401 
                 7-Q137/8-CN 
               
               
                 402 
                 7-Q115/9-CN 
               
               
                 403 
                 7-Q151/9-CN 
               
               
                 404 
                 7-Q138/9-CN 
               
               
                 405 
                 7-Q140/9-CN 
               
               
                 406 
                 7-Q137/9-CN 
               
               
                 407 
                 9-A115/7-CN 
               
               
                 408 
                 9-Q151/7-CN 
               
               
                 409 
                 9-Q138/7-CN 
               
               
                 410 
                 9-Q140/7-CN 
               
               
                 411 
                 9-Q137/7-CN 
               
               
                 412 
                 9-Q175/7-CN 
               
               
                 413 
                 7-Q175/9-CN 
               
               
                 414 
                 7-Q175/8-CN 
               
               
                 415 
                 8-Q175/9-CN 
               
               
                 416 
                 7-CN/8-CN 
               
               
                 417 
                 7-CN/9-CN 
               
               
                 418 
                 8-CN/9-CN 
               
               
                 419 
                 8-Q133/7-CN 
               
               
                 420 
                 8-Q133/9-CN 
               
               
                 421 
                 8-Q133/7-OEt 
               
               
                 422 
                 8-Q133/9-OEt 
               
               
                 423 
                 8-Q133/9-etomet 
               
               
                 424 
                 7-Q135/9-CO 2 H 
               
               
                 425 
                 7-Q133/9-CO 2 H 
               
               
                 426 
                 7-Q135/9-etomet 
               
               
                 427 
                 7-Q135/9-f2meoet 
               
               
                 428 
                 7-CN/8-Q174 
               
               
                 429 
                 7-CN/8-Q153 
               
               
                 430 
                 7-CN/8-Q158 
               
               
                 431 
                 7-CN/8-CO 2 H 
               
               
                 432 
                 8-CN/7-Q174 
               
               
                 433 
                 8-CN/7-Q153 
               
               
                 434 
                 8-CN/7-Q158 
               
               
                 435 
                 8-CN/7-CO 2 H 
               
               
                 436 
                 9-CN/7-Q174 
               
               
                 437 
                 9-CN/7-Q153 
               
               
                 438 
                 9-CN/7-Q158 
               
               
                 439 
                 9-CN/7-CO 2 H 
               
               
                 440 
                 7-CN/9-Q174 
               
               
                 441 
                 7-CN/9-Q153 
               
               
                 442 
                 7-CN/9-Q158 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17   
               
               
                   
               
               
                 443 
                 7-CN/9-CO 2 H 
               
               
                 444 
                 7-CN/8-Q174 
               
               
                 445 
                 7-CN/8-Q153 
               
               
                 446 
                 7-CN/8-Q158 
               
               
                 447 
                 7-CN/8-CO 2 H 
               
               
                 448 
                 7-Q174 
               
               
                 449 
                 7-Q175 
               
               
                 450 
                 7-Q176 
               
               
                 451 
                 7-Q177 
               
               
                 452 
                 7-Q178 
               
               
                 453 
                 7-Q179 
               
               
                 454 
                 7-Q180 
               
               
                 455 
                 8-Q174 
               
               
                 456 
                 8-Q175 
               
               
                 457 
                 8-Q176 
               
               
                 458 
                 8-Q177 
               
               
                 459 
                 8-Q178 
               
               
                 460 
                 8-Q179 
               
               
                 461 
                 8-Q180 
               
               
                 462 
                 9-Q174 
               
               
                 463 
                 9-Q175 
               
               
                 464 
                 9-Q176 
               
               
                 465 
                 9-Q177 
               
               
                 466 
                 9-Q178 
               
               
                 467 
                 9-Q179 
               
               
                 468 
                 9-Q180 
               
               
                 469 
                 7-Q136 
               
               
                 470 
                 7-Q137 
               
               
                 471 
                 7-Q138 
               
               
                 472 
                 7-Q181 
               
               
                 473 
                 7-Q182 
               
               
                 474 
                 7-Q183 
               
               
                 475 
                 7-Q184 
               
               
                 476 
                 7-Q185 
               
               
                 477 
                 7-Q186 
               
               
                 478 
                 8-Q136 
               
               
                 479 
                 8-Q137 
               
               
                 480 
                 8-Q138 
               
               
                 481 
                 8-Q181 
               
               
                 482 
                 8-Q182 
               
               
                 483 
                 8-Q183 
               
               
                 484 
                 8-Q184 
               
               
                 485 
                 8-Q185 
               
               
                 486 
                 8-Q186 
               
               
                 487 
                 7-CN/9-f2etoet 
               
               
                 488 
                 7-CN/9-OEt 
               
               
                 489 
                 7-Q158/9-OCHF 2   
               
               
                 490 
                 7-Q174/9-OCHF 2   
               
               
                 491 
                 7-CO 2 H/9-OCHF 2   
               
               
                 492 
                 7-OCHF 2 /9-CO 2 H 
               
               
                 493 
                 7-cycpro-CH 2 O/9-CO 2 H 
               
               
                 494 
                 7-CN/9-cycpro-CH 2 O 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No. 
                 R 17   
                 R 6   
               
               
                   
               
               
                 495 
                 6-OMe 
                 Q3 
               
               
                 496 
                 8-Cl 
                 Q4 
               
               
                 497 
                 6-Q117 
                 Q6 
               
               
                 498 
                 6-CN 
                 Q8 
               
               
                 499 
                 7-Q117 
                 Q10 
               
               
                 500 
                 6-Me 
                 Q25 
               
               
                 501 
                 8-Q117 
                 Q49 
               
               
                 502 
                 7-OEt 
                 Q6 
               
               
                 503 
                 6-Me/8-CN 
                 Q3 
               
               
                 504 
                 8-Me/7-OMe 
                 Q10 
               
               
                 505 
                 6-Ac 
                 Q4 
               
               
                 506 
                 6-Q117/8-F 
                 Q6 
               
               
                 507 
                 9-Q117 
                 Q8 
               
               
                 508 
                 7-OCHF 2   
                 Q10 
               
               
                 509 
                 9-OMe 
                 Q25 
               
               
                 510 
                 7-CN/8-F 
                 Q49 
               
               
                 511 
                 9-CN/8-F 
                 Q6 
               
               
                 512 
                 7-CN/9-F 
                 Q3 
               
               
                 513 
                 7-CN/8-OMe 
                 Q4 
               
               
                 514 
                 9-CN/8-OMe 
                 Q6 
               
               
                 515 
                 7-CN/8-OMe 
                 Q8 
               
               
                 516 
                 7-CN/8-f2etoet 
                 Q10 
               
               
                 517 
                 9-CN/7-OMe 
                 Q25 
               
               
                 518 
                 9-CN/7-meomet 
                 Q49 
               
               
                 519 
                 9-CN/8-meomet 
                 Q6 
               
               
                 520 
                 7-CN/8-O(i-Pr) 
                 Q6 
               
               
                   
               
            
           
           
               
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No. 
                 R 17   
                 R 6   
               
               
                   
               
               
                 521 
                 6-OMe 
                 Q3 
               
               
                 522 
                 8-Cl 
                 Q4 
               
               
                 523 
                 6-Q117 
                 Q6 
               
               
                 524 
                 6-CN 
                 Q8 
               
               
                 525 
                 7-Q117 
                 Q10 
               
               
                 526 
                 6-Me 
                 Q25 
               
               
                 527 
                 8-Q117 
                 Q49 
               
               
                 528 
                 7-OEt 
                 Q6 
               
               
                 529 
                 6-Me/8-CN 
                 Q3 
               
               
                 530 
                 8-Me/7-OMe 
                 Q10 
               
               
                 531 
                 6-Ac 
                 Q4 
               
               
                 532 
                 6-Q117/8-F 
                 Q6 
               
               
                 533 
                 9-Q117 
                 Q8 
               
               
                 534 
                 6-OPh 
                 Q10 
               
               
                 535 
                 9-OMe 
                 Q25 
               
               
                 536 
                 7-CN/8-F 
                 Q49 
               
               
                 537 
                 9-CN/8-F 
                 Q6 
               
               
                 538 
                 7-CN/9-F 
                 Q3 
               
               
                 539 
                 7-CN/8-OMe 
                 Q4 
               
               
                 540 
                 9-CN/8-OMe 
                 Q6 
               
               
                 541 
                 7-CN/8-meoet 
                 Q8 
               
               
                 542 
                 7-CN/8-f2etoet 
                 Q10 
               
               
                 543 
                 9-CN/7-OMe 
                 Q25 
               
               
                 544 
                 9-CN/7-meomeet 
                 Q49 
               
               
                 545 
                 9-CN/8-meomet 
                 Q6 
               
               
                 546 
                 7-CN/8-O(i-Pr) 
                 Q6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 No. 
                 R 17   
                 R 1   
                 R 2   
               
               
                   
               
               
                 547 
                 6-CO 2 H 
                 Q70 
                 Q3 
               
               
                 548 
                 7-CO 2 H 
                 Q71 
                 Q4 
               
               
                 549 
                 7-CO 2 H/8-OH 
                 Me 
                 Q4 
               
               
                 550 
                 7-CO 2 H/8-OMe 
                 Q82 
                 Q4 
               
               
                 551 
                 7-CO 2 H/8-OEt 
                 Me 
                 Q4 
               
               
                 552 
                 7-CO 2 H/8-F 
                 Me 
                 Q6 
               
               
                 553 
                 7-CO 2 H/9-F 
                 Me 
                 Q6 
               
               
                 554 
                 7-Q117/8-OH 
                 Q173 
                 Q6 
               
               
                 555 
                 7-Q133/8-OMe 
                 meomet 
                 Q6 
               
               
                 556 
                 7-Q133/8-F 
                 etomet 
                 Q13 
               
               
                 557 
                 7-Q135/9-F 
                 meoet 
                 Q13 
               
               
                 558 
                 7-Q138 
                 etoet 
                 Q13 
               
               
                 559 
                 7-Q136 
                 f2etoet 
                 Q3 
               
               
                 560 
                 7-Q137 
                 Q70 
                 Q3 
               
               
                 561 
                 8-CO 2 H 
                 Q71 
                 Q4 
               
               
                 562 
                 8-CO 2 H/7-OH 
                 Q79 
                 Q4 
               
               
                 563 
                 8-CO 2 H/7-OMe 
                 Me 
                 Q6 
               
               
                 564 
                 8-CO 2 H/7-F 
                 Q152 
                 Q6 
               
               
                 565 
                 8-Q133/8-OMe 
                 Me 
                 Q6 
               
               
                 566 
                 8-Q133/8-F 
                 Q159 
                 Q6 
               
               
                 567 
                 8-Q136 
                 Me 
                 Q6 
               
               
                 568 
                 8-Q137 
                 meomet 
                 Q4 
               
               
                 569 
                 9-CO 2 H 
                 etomet 
                 Q13 
               
               
                 570 
                 9-CO 2 H/6-F 
                 meoet 
                 Q10 
               
               
                 571 
                 9-Q117/7-F 
                 etoet 
                 Q13 
               
               
                 572 
                 9-Q133/6F 
                 Me 
                 Q6 
               
               
                   
               
            
           
           
               
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 No. 
                 R 17   
                 R 1   
                 R 2   
               
               
                   
               
               
                 573 
                 6-OMe 
                 Q70 
                 Q3 
               
               
                 574 
                 8-Cl 
                 Q71 
                 Q4 
               
               
                 575 
                 6-Q117 
                 Q79 
                 Q6 
               
               
                 576 
                 6-CN 
                 Q82 
                 Q8 
               
               
                 577 
                 7-Q117 
                 Q152 
                 Q10 
               
               
                 578 
                 6-Me 
                 Q156 
                 Q25 
               
               
                 579 
                 8-Q117 
                 Q159 
                 Q49 
               
               
                 580 
                 7-OEt 
                 Q173 
                 Q6 
               
               
                 581 
                 6-Me/8-CN 
                 meomet 
                 Q3 
               
               
                 582 
                 8-Me/7-OMe 
                 etomet 
                 Q10 
               
               
                 583 
                 6-Ac 
                 meoet 
                 Q4 
               
               
                 584 
                 6-Q117/8-F 
                 etoet 
                 Q6 
               
               
                 585 
                 9-Q117 
                 f2etoet 
                 Q8 
               
               
                 586 
                 6-OPh 
                 Q70 
                 Q10 
               
               
                 587 
                 9-OMe 
                 Q71 
                 Q25 
               
               
                 588 
                 7-CN/8-F 
                 Q79 
                 Q49 
               
               
                 589 
                 9-CN/8-F 
                 Q82 
                 Q6 
               
               
                 590 
                 7-CN/9-F 
                 Q152 
                 Q3 
               
               
                 591 
                 7-CN/8-OMe 
                 Q156 
                 Q4 
               
               
                 592 
                 9-CN/8-OMe 
                 Q159 
                 Q6 
               
               
                 593 
                 7-CN/8-meoet 
                 Q173 
                 Q8 
               
               
                 594 
                 7-CN/8-feetoet 
                 meomet 
                 Q10 
               
               
                 595 
                 9-CN/7-OMe 
                 etomet 
                 Q25 
               
               
                 596 
                 9-CN/7-meomet 
                 meoet 
                 49 
               
               
                 597 
                 9-CN/8-meomet 
                 etoet 
                 Q6 
               
               
                 598 
                 7-CN/8-O(i-Pr) 
                 f2oetet 
                 Q6 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17a   
               
               
                   
               
               
                 599 
                 CO 2 H 
               
               
                 600 
                 Q133 
               
               
                 601 
                 Q135 
               
               
                 602 
                 Q174 
               
               
                 603 
                 Q175 
               
               
                 604 
                 Q207 
               
               
                 605 
                 CN 
               
               
                   
               
            
           
           
               
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17a   
               
               
                   
               
               
                 606 
                 CO 2 H 
               
               
                 607 
                 Q133 
               
               
                 608 
                 Q135 
               
               
                 609 
                 Q174 
               
               
                 610 
                 Q175 
               
               
                 611 
                 Q207 
               
               
                 612 
                 CN 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                   
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17a   
               
               
                   
               
               
                 613 
                 CO 2 H 
               
               
                 614 
                 Q133 
               
               
                 615 
                 Q135 
               
               
                 616 
                 Q174 
               
               
                 617 
                 Q175 
               
               
                 618 
                 Q207 
               
               
                 619 
                 CN 
               
               
                   
               
            
           
           
               
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17a   
               
               
                   
               
               
                 620 
                 CO 2 H 
               
               
                 621 
                 Q133 
               
               
                 622 
                 Q135 
               
               
                 623 
                 Q174 
               
               
                 624 
                 Q175 
               
               
                 625 
                 Q207 
               
               
                 626 
                 CN 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                   
                   
               
               
                 No. 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                   
                   
               
               
                 627 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 628 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 629 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 630 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 631 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 632 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 633 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 634 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 635 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 636 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 637 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 638 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 639 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 640 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 641 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 642 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 643 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 644 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 17   
               
               
                   
               
               
                 645 
                 7-f2etoet/9-CO 2 H 
               
               
                 646 
                 7-O-(i-Pr)/9-CO 2 H 
               
               
                 647 
                 7-f2meomet/9-CO 2 H 
               
               
                 648 
                 7-f2etomet/9-CO 2 H 
               
               
                 649 
                 7-OEt/9-CO 2 H 
               
               
                 650 
                 7-etomet/9-CO 2 H 
               
               
                 651 
                 7-OMe/9-CO 2 H 
               
               
                 652 
                 7-Q187 
               
               
                 653 
                 8-Q187 
               
               
                 654 
                 7-Q188 
               
               
                 655 
                 7-Q189 
               
               
                 656 
                 7-Q190 
               
               
                 657 
                 7-Q172 
               
               
                 658 
                 8-Q172 
               
               
                 659 
                 7-CF 3 /9-CO 2 H 
               
               
                 660 
                 9-CF 3 /7-CO 2 H 
               
               
                 661 
                 8-CF 3 /7-CO 2 H 
               
               
                 662 
                 6-F/8-F/9-F/7-CO 2 H 
               
               
                 663 
                 7-Q134/9-CO 2 H 
               
               
                 664 
                 7-Q191 
               
               
                 665 
                 7-Q192 
               
               
                 666 
                 8-Q191 
               
               
                 667 
                 8-Q192 
               
               
                 668 
                 7-Q182/9-CO 2 H 
               
               
                 669 
                 9-Q182/7-CN 
               
               
                 670 
                 7-CN/9-Q193 
               
               
                 671 
                 7-Q135/9-Q193 
               
               
                 672 
                 7-CF 3 /9-Q193 
               
               
                 673 
                 7-Q194 
               
               
                 674 
                 7-Q195 
               
               
                 675 
                 7-Q196 
               
               
                 676 
                 7-Q194/9-CN 
               
               
                 677 
                 7-Q195/9-CN 
               
               
                 678 
                 7-Q196/9-CN 
               
               
                 679 
                 7-Q197 
               
               
                 680 
                 7-Q198 
               
               
                 681 
                 7-Q199 
               
               
                 682 
                 7-Q200 
               
               
                 683 
                 7-Q201 
               
               
                 684 
                 7-Q202 
               
               
                 685 
                 7-Q203 
               
               
                 686 
                 7-Q204 
               
               
                 687 
                 7-Q205 
               
               
                 688 
                 7-Q206 
               
               
                 689 
                 7-Q198/9-CO 2 H 
               
               
                 690 
                 7-Q203/9-CO 2 H 
               
               
                 691 
                 7-Q199/9-CN 
               
               
                 692 
                 7-Q200/9-CN 
               
               
                 693 
                 7-Q201/9-CN 
               
               
                 694 
                 7-Q206/9-CN 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
            
               
                 No. 
                 R 2   
               
               
                   
               
               
                 695 
                 Q153 
               
               
                 696 
                 Q174 
               
               
                 697 
                 Q175 
               
               
                 698 
                 Q176 
               
               
                 699 
                 Q177 
               
               
                 700 
                 Q178 
               
               
                 701 
                 Q179 
               
               
                 702 
                 Q180 
               
               
                 703 
                 Q163 
               
               
                 704 
                 Q164 
               
               
                 705 
                 Q187 
               
               
                 706 
                 Q188 
               
               
                 707 
                 Q189 
               
               
                 708 
                 Q190 
               
               
                 709 
                 Q191 
               
               
                 710 
                 Q192 
               
               
                 711 
                 Q207 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No. 
                 R 17   
                 R 6   
               
               
                   
               
               
                 712 
                 7-Q136/6-F 
                 Q3 
               
               
                 713 
                 7-Q138/8-F 
                 Q4 
               
               
                 714 
                 7-Q159/8-OMe 
                 Q6 
               
               
                 715 
                 7-Q162/8-CN 
                 Q8 
               
               
                 716 
                 7-Q137/8-F 
                 Q10 
               
               
                 717 
                 7-Q137/8-OMe 
                 Q13 
               
               
                 718 
                 7-Q137/6,8-F 
                 Q3 
               
               
                 719 
                 7-Q140/8-F 
                 Q4 
               
               
                 720 
                 7-Q140/9-F 
                 Q5 
               
               
                 721 
                 7-Q151/6-F 
                 Q10 
               
               
                 722 
                 7-Q151/9-CN 
                 Q13 
               
               
                 723 
                 7-Q152/8-OMe 
                 Q4 
               
               
                 724 
                 7-Q152/9-F 
                 Q4 
               
               
                 725 
                 7-Q158/8-F 
                 Q10 
               
               
                 726 
                 7-Q158/9-F 
                 Q13 
               
               
                 727 
                 8-Q138/6-F 
                 Q3 
               
               
                 728 
                 8-Q138/7-F 
                 Q4 
               
               
                 729 
                 8-Q137/7-OMe 
                 Q6 
               
               
                 730 
                 8-Q140/7-CN 
                 Q8 
               
               
                 731 
                 8-Q165/7-F 
                 Q10 
               
               
                 732 
                 8-Q151/7-OMe 
                 Q13 
               
               
                 733 
                 8-Q152/6-F 
                 Q3 
               
               
                 734 
                 8-Q158/8-F 
                 Q4 
               
               
                 735 
                 8-Q140/9-F 
                 Q5 
               
               
                 736 
                 8-Q159/7-CN 
                 Q10 
               
               
                 737 
                 9-Q137/6-F 
                 Q13 
               
               
                 738 
                 9-Q137/8-OMe 
                 Q4 
               
               
                 739 
                 9-Q151/7-OMe 
                 Q4 
               
               
                 740 
                 9-Q152/7-F 
                 Q10 
               
               
                 741 
                 9-Q158/8-F 
                 Q13 
               
               
                 742 
                 7-Q207/8-F 
                 Q13 
               
               
                 743 
                 7-Q207/9-F 
                 Q13 
               
               
                 744 
                 7-Q207/9-CN 
                 Q13 
               
               
                 745 
                 7-Q207/9-CO 2 H 
                 Q13 
               
               
                 746 
                 7-Q207/9-OMe 
                 Q13 
               
               
                 747 
                 8-Q207/7-F 
                 Q13 
               
               
                 748 
                 8-Q207/9-F 
                 Q13 
               
               
                 749 
                 8-Q207/9-CN 
                 Q13 
               
               
                 750 
                 8-Q207/9-OMe 
                 Q13 
               
               
                 751 
                 7-CO 2 H/9-CO 2 H 
                 Q13 
               
               
                 752 
                 8-CO 2 H/7-F 
                 Q13 
               
               
                 753 
                 8-CO 2 H/9-F 
                 Q13 
               
               
                 754 
                 8-CO 2 H/9-OMe 
                 Q13 
               
               
                 755 
                 8-CO 2 H/9-CN 
                 Q13 
               
               
                 756 
                 7-CO 2 H/9-OMe 
                 Q13 
               
               
                 757 
                 8-Q207/7-CN 
                 Q13 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No. 
                 R 17   
                 R 1   
               
               
                   
               
               
                 758 
                 7-CN 
                 Q138 
               
               
                 759 
                 7-CN/8-F 
                 Q138 
               
               
                 760 
                 7-CN/9-OMe 
                 Q138 
               
               
                 761 
                 7-CN/8-F 
                 Q136 
               
               
                 762 
                 7-CN 
                 Q137 
               
               
                 763 
                 7-CN/8-F 
                 Q115 
               
               
                 764 
                 7-CN 
                 Q151 
               
               
                 765 
                 7-CN/8-F 
                 Q158 
               
               
                 766 
                 7-CN/9-OMe 
                 Q151 
               
               
                 767 
                 7-CN/9-OMe 
                 Q158 
               
               
                 768 
                 7-CN/9-OMe 
                 Q115 
               
               
                   
               
            
           
         
       
     
      When in each of the above compounds having compound numbers 1 to 768, the portion corresponding to Y—NH 2  described in the item [1] is an unsubstituted or substituted 3-aminopyrrolidin-1-yl group, an unsubstituted or substituted 3-aminopiperidin-1-yl group or an unsubstituted or substituted (3-amino)hexahydroazepin-1-yl group, bicyclic pyrazole derivatives whose amino group at the 3-position has an absolute configuration represented by the following formula (F 1 ) are more preferable.  
                 
 
 wherein m and R 7  are as defined in the item [1]. 
 
      When in each of the above compounds having compound numbers 1 to 768, the portion corresponding to Y—NH 2  described in the item [1] is an unsubstituted or substituted (2-aminocycloalkyl)amino group, compounds whose amino groups at the 1-position and 2-position have an absolute configuration represented by the following formula (F 2 ) or (F 3 ) are more preferable.  
                 
 
 wherein n and R 8  are as defined in the item [1]. 
 
      Compounds whose amino groups at the 1-position and 2-position have an absolute configuration represented by the following formula (F 4 ) are still more preferable.  
                 
 
 wherein n and R 8  are as defined in the item [1]. 
 
      In the following description, a bond shown by a wedge-shaped solid or broken line as in the formula (J 1 ) and formula (J 2 ) indicates the absolute configuration of an amino group, and a bond shown by a thick line as in the formula (J 3 ) indicates the relative configuration of an amino group (for example, the formula (J 3 ) represents a (±)-cis form).  
                 
 
 wherein n and R 8  are as defined in the item [1]. 
 
      In the compounds, among the above compounds having compound numbers 1 to 768, in which each of the portions corresponding to R 1 , R 2  and R 4 , respectively, described in the item [1], or its partial structure is “an optionally substituted alkoxycarbonyl group”, “Ian optionally substituted cycloalkoxycarbonyl group”, “an optionally substituted aryloxycarbonyl group” or “an optionally substituted aralkyloxycarbonyl group”, each of the substituents described above is converted to “a carboxyl group” in some cases under physiological conditions in a living body by oxidation, reduction, hydrolysis or the like by an enzyme, or hydrolysis by acid in the stomach, or the like.  
      A process for producing the compound represented by the formula (I) of the present invention is explained below with reference to examples, which should not be construed as limiting the scope of the invention. In the present specification, the following abbreviations are used in some cases for the simplification of description.  
      Boc: tert-butoxycarbonyl group  
      Cbz: benzyloxycarbonyl group  
      TMS: trimethylsilyl group  
      TBS: tert-butyldimethylsilyl group  
      SEM: 2-[(trimethylsilyl)ethoxy]methyl group  
      Ac: acetyl group  
      Me: methyl group  
      Et: ethyl group  
      Pr: propyl group  
      i-Pr: isopropyl group  
      Bu: butyl group  
      i-Bu: isobutyl group  
      t-Bu: t-butyl group  
      Ph: phenyl group  
      Bn: benzyl group  
      Ms: methanesulfonyl group  
      TFA: trifluoroacetic acid  
      The compound represented by the formula (I) may be synthesized from a well-known compound by a combination of well-known synthesis processes. It may be synthesized, for example, by any of the following processes.  
      Production Process 1  
      A compound of the formula (1-17) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein m, n, R 6 , R 7 , R 8  and Y are as defined above; X 1  is a leaving group (for example, a bromine atom, a chlorine atom, an iodine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy); R 20  is methyl, ethyl, propyl, 2-propyl or benzyl; R 30  is Boc or Cbz; R 40  is methyl or ethyl; R 50  is a hydrogen atom, methyl or ethyl; and R 55  is acetyl or benzoyl. 
 
 1) Step 1 
 
      A compound (1-3) may be produced from a compound (1-1) by the same production process as described in literature (for example, Bioorg. Med. Chem. Lett. 12, 653 (2002), Chem. Pharm. Bull. 45, 2005 (1997), Tetrahedron Letters 39, 7983 (1998), Tetrahedron 46, 7803 (1990), Tetrahedron Letters 32, 691 (1991), Tetrahedron 51, 5369 (1995), J. Med. Chem. 38, 3236 (1995) and J. Heterocycl. Chem. 24, 275 (1987)).  
      2) Step 2  
      A compound (1-8) may be produced from the compound (1-3) by the following process A or B.  
      A: A compound (1-8) may be produced by reacting the compound (1-3) with a compound (1-4) or a compound (1-5) in an inert solvent in the presence or absence of an additive and in the presence or absence of a base. The additive includes, for example, 4-(dimethylamino)pyridine. The base includes, for example, diisopropylethylamine, triethylamine, pyridine, N-methylmorpholine and 1-methylpiperidine. Preferable examples thereof are diisopropylethylamine and triethylamine. The amount of the base used is usually chosen in the range of 1 to 10 equivalents per equivalent of the compound (1-3). The inert solvent includes, for example, alcohol solvents (e.g. ethanol, methanol and 2-propanol), ether solvents (e.g. 1,4-dioxane), and mixed solvents thereof. The reaction temperature may be chosen in the range of about 50° C. to about 200° C. It is also possible to carry out the reaction in a closed reaction vessel such as an autoclave.  
      B: A compound (1-8) may be produced by reacting the compound (1-3) with a compound (1-6) or a compound (1-7) in an inert solvent in the presence or absence of an additive and in the presence or absence of a base. The additive includes, for example, 4-(dimethylamino)pyridine. The base includes, for example, diisopropylethylamine, triethylamine, pyridine and N-methylmorpholine. A preferable example thereof is diisopropylethylamine. The amount of the base used is usually chosen in the range of 1 to 10 equivalents per equivalent of the compound (1-3). The inert solvent includes, for example, N-methyl-2-piperidone, N-methyl-2-pyrrolidinone, alcohol solvents (e.g. ethanol, methanol and 2-propanol), N,N-dimethylformamide, toluene, and mixed solvents thereof. Preferable examples thereof are N-methyl-2-piperidone and N-methyl-2-pyrrolidinone. The reaction temperature may be chosen in the range of about 50° C. to about 200° C. It is also possible to carry out the reaction in a closed reaction vessel such as an autoclave.  
      3) Step 3  
      A compound (1-10) may be produced by reacting the compound (1-8) with a compound (1-9) in an inert solvent in the presence or absence of a base (see, for example, J. Heterocycl. Chem. 37, 1033 (2000), J. Chem. Soc., Perkin Trans. 1, 13, 1833 (1999) and J. Med. Chem. 38, 3838 (1995)). The amount of the compound (1-9) used is usually chosen in the range of 1 to 3 equivalents per equivalent of the compound of the formula (1-8). The base includes, for example, alkali carbonates (e.g. potassium carbonate, sodium carbonate, potassium hydrogencarbonate and sodium hydrogencarbonate), alkali hydrides (e.g. sodium hydride and potassium hydride) and alkali hydroxides (e.g. potassium hydroxide and sodium hydroxide). A preferable example thereof is potassium carbonate. The amount of the base used is usually chosen in the range of 1 to 5 equivalents per equivalent of the compound (1-8). The inert solvent includes, for example, aprotic solvents (e.g. N,N-dimethylformamide and dimethyl sulfoxide), ether solvents (e.g. diethyl ether, tetrahydrofuran and 1,4-dioxane), ketones (e.g. acetone), and mixed solvents thereof. Preferable examples thereof are N,N-dimethylformamide and dimethyl sulfoxide. The reaction temperature may be chosen in the range of about 10° C. to about 120° C.  
      In general, compounds having a R 6 CH 2  group introduced into a different nitrogen atom can also be produced as by-products in the production of the compound (1-10). The by-products can easily be removed by a conventional purification method.  
      4) Step 4  
      A compound (1-11) may be produced from the compound (1-10) by the same production process as described in literature (for example, WO02/068420).  
      5) Step 5  
      A compound (1-12) may be produced from the compound (1-11) by the same production process as described in literature (for example, WO99/8, Tetrahedron Letters 38, 7963 (1997), Bioorg. Med. Chem. Lett. 12, 543 (2002), Heterocycles 57, 123 (2002), Tetrahedron Letters 41, 9957 (2000) and Tetrahedron Letters 42, 2201 (2001)).  
      6) Step 6  
      A compound (1-14) may be produced from the compound (1-12) by the same production process as described in literature (for example, Tetrahedron Letters 43, 5079 (2002)).  
      7) Step 7  
      A compound (1-15) may be produced by reacting the compound (1-14) in an inert solvent in the presence or absence of an additive and in the presence or absence of a base. The additive includes, for example, 4-(dimethylamino)pyridine. The base includes, for example, alkali hydroxides (e.g. potassium hydroxide and sodium hydroxide), alkali hydrides (e.g. sodium hydride and potassium hydride) and alkoxy alkalis (sodium methoxide, sodium ethoxide and potassium t-butoxide). Preferable examples thereof are sodium methoxide and sodium ethoxide. The amount of the base used is usually chosen in the range of 1 equivalent to large excess equivalents per equivalent of the compound (1-14). The inert solvent includes, for example, alcohol solvents (e.g. ethanol, methanol and 2-propanol), ether solvents (e.g. tetrahydrofuran), and mixed solvents thereof. The reaction temperature may be chosen in the range of about 10° C. to about 100° C.  
      8) Step 8  
      When R 30  is Boc in the compound (1-15), a compound (1-16) may be produced by removing the Boc group of the compound (1-15) to effect deprotection, in an inert solvent in the presence of an acid. The acid includes, for example, hydrochloric acid, sulfuric acid and trifluoroacetic acid. Preferable examples thereof are hydrochloric acid and trifluoroacetic acid. The amount of the acid used is usually chosen in the range of 1 equivalent to large excess equivalents per equivalent of the compound (1-15). The inert solvent includes, for example, halogenated hydrocarbon solvents (e.g. dichloromethane, dichloroethane and chloroform), ether solvents (e.g. 1,4-dioxane), and mixed solvents thereof. The reaction temperature may be chosen in the range of about −20° C. to about 30° C.  
      When R 30  is Cbz, a compound (1-16) may be produced from the compound (1-15) by the same production process as described in literature (for example, J. Am. Chem. Soc. 85, 2149 (1963), Tetrahedron Lett. 41, 3029 (2000) and Tetrahedron Lett. 36, 8677 (1995)).  
      9) Step 9  
      The compound (1-17) may be produced from the compound (1-16) by the same production process as described in literature (for example, J. Org. Chem. 61, 215 (1996), J. Org. Chem. 61, 9437 (1996) and J. Org. Chem. 59, 6147 (1994)).  
      Production Process 2  
      Compounds of the formula (2-3), formula (2-4) and formula (2-7) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 40 , R 50  and Y are as defined above; R 35 OC(O) is “an optionally substituted alkoxycarbonyl group”, “an optionally substituted aryloxycarbonyl group”, “an optionally substituted aralkyloxycarbonyl group”, “an optionally substituted cycloalkyloxycarbonyl group” or “an esterified carboxyl group”; and X 2  is a leaving group (for example, a bromine atom, a chlorine atom, an iodine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy). 
 
 1) Step 1 
 
      A compound (2-1) may be produced from a compound (1-15) by the same production process as described in the step 9 in the production process 1.  
      2) Step 2  
      A compound (2-2) may be produced from the compound (2-1) by the same production process as described in literature (for example, Heterocycles 53, 797 (2000), Bioorg. Med. Chem. Lett. 7, 739 (1997) and Org. Prep. Proced. Int. 26, 429 (1994)).  
      When the compound (2-3) is produced by deprotection by the removal of the Boc group of the compound (2-2) in this step, the compound (2-2) may be produced from the compound (2-3) by the same process as that described in literature (for example, Protective Groups in Organic Synthesis 2nd Edition (John Wiley &amp; Sons, Inc.)), or the like.  
      3) Step 3  
      The compound (2-3) may be produced from the compound (2-2) by the same production process as described in the step 8 in the production process 1.  
      4) Step 4  
      The compound (2-4) may be produced from the compound (2-2) by the same production process as described in literature (for example, Tetrahedron Lett. 38, 1241 (1997) and Synth. Commun. 22, 2811 (1992)).  
      When a compound (2-5) represented by the formula:  
                 
 
 wherein R 6 , R 30 , R 50  and Y are as defined above, is produced by the protection of the compound (2-4) by R 30  in this step, the compound (2-4) may be produced from the compound (2-5) by the same production process as described in the step 8 in the production process 1. 
 
 5) Step 5 
 
      A compound (2-6) may be produced from a compound (2-1) by the same production process as described in the step 1 in the production process 3. As a compound (2-5), a commercial reagent may be used, or the compound (2-5) may be produced by the same production process as described in literature (for example, WO03/027098, WO00/06581, and R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 1989).  
      6) Step 6  
      The compound (2-7) may be produced from the compound (2-6) by the same production process as described in the step 8 in the production process 1.  
      Production Process 3  
      Compounds of the formula (3-4) and the formula (3-6) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 35 , R 40 , R 50 , Y 5  and X 2  are as defined above; X 3  is a leaving group (for example, a bromine atom, a chlorine atom, an iodine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy); and R 60  is “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”. 
 
 1) Step 1 
 
      A compound (3-2) may be produced by reacting a compound (1-15) with a compound (3-1) in an inert solvent in the presence of a base. The amount of the compound (3-1) used is usually chosen in the range of 1 to 3 equivalents per equivalent of the compound (1-15). The base includes, for example, alkali carbonates (e.g. potassium carbonate, sodium carbonate, potassium hydrogencarbonate and sodium hydrogencarbonate), alkali hydroxides (e.g. potassium hydroxide and sodium hydroxide), alkali hydrides (e.g. sodium hydride and potassium hydride) and alkoxy alkalis (e.g. potassium t-butoxide). Preferable examples thereof are potassium carbonate and sodium hydride. The amount of the base used is usually chosen in the range of 1 to 5 equivalents per equivalent of the compound (1-15). The inert solvent includes, for example, aprotic solvents (e.g. N,N-dimethylformamide and dimethyl sulfoxide), ether solvents (e.g. diethyl ether, tetrahydrofuran and 1,4-dioxane), ketones (e.g. acetone), and mixed solvents thereof. A preferable example thereof is N,N-dimethylformamide. The reaction temperature may be chosen in the range of about 10° C. to about 100° C.  
      2) Step 2  
      A compound (3-3) may be produced from the compound (3-2) by the same production process as described in the step 9 in the production process 1.  
      3) Step 3  
      The compound (3-4) may be produced from the compound (3-3) by the same production process as described in the step 8 in the production process 1.  
      4) Step 4  
      A compound (3-5) may be produced from the compound (3-3) by the same production process as described in the step 5 in the production process 2.  
      5) Step 5  
      The compound (3-6) may be produced from the compound (3-5) by the same production process as described in the step 8 in the production process 1.  
      Production Process 4  
      A compound of the formula (4-1) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 40 , R 50 , R 60  and Y are as defined above. 
 
 1) Step 1 
 
      The compound (4-1) may be produced from a compound (3-2) by the same production process as described in the step 8 in the production process 1.  
      Production Process 5  
      A compound of the formula (5-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 50  and Y are as defined above; R 65  is “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”; and X 4  is a leaving group (for example, a bromine atom, a chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy). 
 
 1) Step 1 
 
      A compound (5-2) may be produced from a compound (2-1) by the same production process as described in the step 1 in the production process 3.  
      2) Step 2  
      The compound (5-3) may be produced from the compound (5-2) by the same production process as described in the step 8 in the production process 1.  
      Production Process 6  
      A compound of the formula (6-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 50 , R 60  and Y are as defined above; and R 80 R 70 NC(O) is “an optionally substituted carbamoyl group”. 
 
 1) Step 1 
 
      A compound (6-2) may be produced from a compound (3-3) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989)).  
      2) Step 2  
      The compound (6-3) may be produced from the compound (6-2) by the same production process as described in the step 8 in the production process 1.  
      Production Process 7  
      A compound of the formula (7-4) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 50 , R 60  and Y are as defined above; M 1  is lithium, magnesium chloride or magnesium bromide; and C(O)R 90  is “an optionally substituted alkylcarbonyl group”, “an optionally substituted aroyl group” or “an optionally substituted heteroarylcarbonyl group”. 
 
 1) Step 1 to Step 2 
 
      A compound (7-3) may be produced from a compound (3-3) by the same production process as described in literature (for example, Bioorg. Med. Chem. Lett. 11, 2951 (2001), Tetrahedron Letters 42, 8955 (2001), Synthesis 1852 (2000), Organic Letters 2, 4091 (2000), Tetrahedron Letters 42, 5609 (2001), Synthesis 2239 (2001), Synlett 5, 715 (2002), J. Org. Chem. 67, 5032 (2002), Bioorg. Med. Chem. Lett. 11, 287 (2001) and Tetrahedron Letters 42, 3763 (2001)). As a compound (7-2), a commercial one may be used, or the compound (7-2) may be produced by the process described, for example, in Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 25, Maruzen Co., Ltd.  
      2) Step 3  
      The compound (7-4) may be produced from the compound (7-3) by the same production process as described in the step 8 in the production process 1.  
      Production Process 8  
      A compound of the formula (8-5) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 40 , R 50 , R 60  and Y are as defined above; and R 100 O is the “optionally substituted aryloxy group” or “optionally substituted alkoxy group” exemplified as the substituent(s) of the “optionally substituted alkyl group”
 
 1) Step 1 
 
      A compound (8-1) may be produced from a compound (3-2) by the same production process as described, for example, in Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 20 and Vol. 22, Maruzen Co., Ltd.  
      2) Step 2  
      A compound (8-2) may be produced from the compound (8-1) by the same production process as described, for example, in Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 19, Maruzen Co., Ltd.  
      3) Step 3  
      A compound (8-4) may be produced from the compound (8-2) by the same production process as described, for example, in Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 20, Maruzen Co., Ltd.  
      4) Step 4  
      The compound (8-5) may be produced from the compound (8-4) by the same production process as described in the step 8 in the production process 1.  
      Production Process 9  
      A compound of the formula (9-6) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 20 , R 30  and Y are as defined above; and R 110  is a hydrogen atom, “an optionally substituted alkyl group”, “an optionally substituted cycloalkyl group”, “an optionally substituted aryl group”, “an optionally substituted aralkyl group”, “an optionally substituted heteroaryl group” or “an optionally substituted heteroarylalkyl group”, or a trimethylsilyl group. 
 
 1) Step 1 
 
      A compound (9-1) may be produced from a compound (1-12) by the same production process as described in the step 9 in the production process 1.  
      2) Step 2  
      A compound (9-2) may be produced from the compound (9-1) by the same production process as described in the step 2 in the production process 2.  
      3) Steps 3 to 4  
      A compound (9-5) may be produced from the compound (9-2) by the same production process as described in literature (for example, Chem. Pharm. Bull. 44, 288 (1996), J. Med. Chem. 34, 778 (1991) and Tetrahedron 49, 557 (1993)). The step 3 may be carried out with reference to the production process described in literature (for example, Chem. Rev. 103, 1979 (2003) and Chem. Rev. 103, 1875 (2003)).  
      4) Step 5  
      The compound (9-6) may be produced from the compound (9-5) by the same production process as described in the step 8 in the production process 1.  
      Production Process 10  
      Compounds of the formula (10-3), formula (10-6) and formula (10-8) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 110  and Y are as defined above; R 120  is methyl, ethyl, propyl or 2-propyl; R 130  is methyl or ethyl; and each of X 5  and X 6  is a leaving group (for example, a bromine atom, a chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy). 
 
 1) Step 1 
 
      A compound (10-2) may be produced from a compound (9-5) by the same production process as described in the step 1 in the production process 3.  
      2) Step 2  
      The compound (10-3) may be produced from the compound (10-2) by the same production process as described in the step 8 in the production process 1.  
      3) Step 3  
      A compound (10-5) may be produced from a compound (9-5) by the same production process as described in the step 1 in the production process 3.  
      4) Step 4  
      The compound (10-6) may be produced from the compound (10-5) by the same production process as described in the step 8 in the production process 1.  
      5) Step 5  
      A compound (10-7) may be produced from the compound (10-5) by the same production process as described in the step 9 in the production process 1.  
      6) Step 6  
      The compound (10-8) may be produced from the compound (10-7) by the same production process as described in the step 8 in the production process 1.  
      Production Process 11  
      A compound of the formula (11-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 110  and Y are as defined above; and R 140 R 150 NC(O) is the “optionally substituted carbamoyl group” exemplified as the substituent(s) of the “optionally substituted alkyl group”. 
 
 1) Step 1 
 
      A compound (11-2) may be produced from a compound (10-7) by the same production process as described in the step 1 in the production process 6.  
      2) Step 2  
      The compound (11-3) may be produced from the compound (11-2) by the same production process as described in the step 8 in the production process 1.  
      Production Process 12  
      A compound of the formula (12-4) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 110  and Y are as defined above; M 2  is lithium, magnesium chloride or magnesium bromide; and C(O)R 160  is the “optionally substituted aroyl group” or “optionally substituted nitrogen-containing heteroarylcarbonyl group” exemplified as the substituent(s) of the “optionally substituted alkyl group”. 
 
 1) Step 1 to Step 2 
 
      A compound (12-3) may be produced from a compound (10-7) by the same production process as described in the step 1 to step 2 in the production process 7. As a compound (12-2), a commercial one may be used, or the compound (12-2) may be produced by the process described, for example, in Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 25, Maruzen Co., Ltd.  
      2) Step 3  
      The compound (12-4) may be produced from the compound (12-3) by the same production process as described in the step 8 in the production process 1.  
      Production Process 13  
      A compound of the formula (13-5) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 40 , R 50  and Y are as defined above; R 170  is “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”; and X 7  is a leaving group (for example, a bromine atom, a chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy). 
 
 1) Step 1 
 
      A compound (13-2) may be produced from a compound (1-15) by the same production process as described in the step 1 in the production process 3.  
      2) Step 2  
      A compound (13-3) may be produced from the compound (13-2) by the same production process as described in the step 9 in the production process 1.  
      3) Step 3  
      A compound (13-4) may be produced from the compound (13-3) by the same production process as described in the step 2 in the production process 2.  
      4) Step 4  
      The compound (13-5) may be produced from the compound (13-4) by the same production process as described in the step 4 in the production process 2.  
      When a compound (13-6) represented by the formula:  
                 
 
 wherein R 6 , R 30 , R 50 , R 170  and Y are as defined above, is produced by the protection of the compound (13-5) by R 30  in this step, the compound (13-5) may be produced from the compound (13-6) by the same production process as described in the step 8 in the production process 1. 
 
 Production Process 14 
 
      Compounds of the formula (14-5) and the formula (14-7) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 50 , R 170  and Y are as defined above; R 180 -Q 1  is “an optionally substituted aryloxy group”, “an optionally substituted arylthio group” or “an optionally substituted heteroaryloxy group”; R 180 -Q 2  is “an optionally substituted arylsulfonyl group”; E 1  is a chlorine atom or a bromine atom; and M 3  is lithium, sodium, potassium or cesium. 
 
 1) Step 1 
 
      A compound (14-1) may be produced from a compound (13-3) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989) and Eur. J. Org. Chem. 1353 (2000)). When a compound (14-8) represented by the formula:  
                 
 
 wherein R 6 , R 50 , R 170  and Y are as defined above, is produced by deprotection by the removal of Boc for R 30  of the compound (14-1) in this step, the compound (14-1) may be produced by the following process. That is, the compound (14-8) is reacted with di-tert-butyl dicarbonate in an inert solvent in the presence of a base. The amount of di-tert-butyl dicarbonate used is usually chosen in the range of 3 to 6 equivalents per equivalent of the compound (14-8). The base includes, for example, inorganic bases such as sodium hydroxide, potassium carbonate, etc.; and organic bases such as triethylamine, etc. The inert solvent includes, for example, ether solvents (e.g. tetrahydrofuran and 1,4-dioxane). The reaction temperature is chosen in the range of about −10° C. to about 40° C. 
 
 2) Step 2 
 
      A compound (14-2) may be produced from the compound (14-1) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989) and Eur. J. Org. Chem. 1353 (2000)). When the Boc group of the compound (14-2) is removed, namely, deprotection is caused, the compound (14-2) may be produced by introduction of Boc by the same production process as described in the step 1 in the production process 14.  
      3) Step 3  
      A compound (14-4) may be produced from the compound (14-2) by the same production process as described in literature (for example, Heterocycles 52, 253 (2000)).  
      4) Step 4  
      The compound (14-5) may be produced from the compound (14-4) by the same production process as described in the step 8 in the production process 1.  
      5) Step 5  
      When Q 1  of the compound (14-4) is a sulfur atom, a compound (14-6) may be produced by the conversion of Q 1  to sulfone by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989) and Eur. J. Org. Chem. 1353 (2000)).  
      6) Step 6  
      The compound (14-7) may be produced from the compound (14-6) by the same production process as described in the step 8 in the production process 1.  
      Production Process 15  
      A compound of the formula (15-5) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30  and Y are as defined above; R 190  is “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”; each of R 200  and R 210 , which may be the same or different, is a hydrogen atom, a fluorine atom, methyl or ethyl; and X 8  is a chlorine atom or a bromine atom. 
 
 1) Step 1 
 
      A compound (15-2) may be produced from a compound (9-1) by the same production process as described in the step 1 in the production process 6.  
      2) Step 2  
      A compound (15-4) may be produced from the compound (15-2) by the same production process as described in literature (for example, Chem. Pharm. Bull. 40, 982 (2000)).  
      3) Step 3  
      The compound (15-5) may be produced from the compound (15-4) by the same production process as described in the step 8 in the production process 1.  
      Production Process 16  
      A compound of the formula (16-7) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein the compound (16-1) corresponds to the compound (15-4) described in the production process 15 when R 210  is a hydrogen atom; R 6 , R 30 , R 190 , R 200  and Y are as defined above; R 230 -Q 3  is “an optionally substituted aryloxy group”, “an optionally substituted arylthio group” or “an optionally substituted heteroaryloxy group”; R 230 -Q 4  is “an optionally substituted arylsulfonyl group”; E 2  is a chlorine atom or a bromine atom; and M 4  is lithium, sodium, potassium or cesium. 
 
 1) Step 1 
 
      A compound (16-2) may be produced from the compound (16-1) by the same production process as described in literature (for example, Heterocycles 37, 1147 (1994), J. Heterocycl. Chem. 34, 659 (1997), Tetrahedron 54, 9207 (1998), Chem. Pharm. Bull. 40, 846 (1992), Tetrahedron Lett. 25, 5043 (1984) and Tetrahedron Lett. 25, 4007 (1984)).  
      2) Step 2  
      A compound (16-4) may be produced from the compound (16-2) by the same production process as described in literature (for example, Heterocycles 52, 253 (2000), Tetrahedron Lett. 33, 2027 (1992) and Synthesis 11, 921 (1980)).  
      3) Step 3  
      A compound (16-5) may be produced from the compound (16-4) by the same production process as described in the step 8 in the production process 1.  
      4) Step 4  
      When Q 1  of the compound (16-4) is a sulfur atom, a compound (16-6) may be produced from the compound (16-4) by the same production process as described in the step 5 in the production process 14.  
      5) Step 5  
      The compound (16-7) may be produced from the compound (16-6) by the same production process as described in the step 8 in the production process 1.  
      Production Process 17  
      A compound of the formula (17-6) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 190  and Y are as defined above; R 215  is a hydrogen atom, methyl, ethyl or “an alkoxycarbonylmethyl group”; and R 240  is methyl, ethyl, propyl, 2-propyl or butyl. 
 
 1) Step 1 to Step 2 
 
      A compound (17-3) may be produced from a compound (15-2) by the same production process as described in literature (for example, Bioorg. Med. Chem. Lett. 12, 827 (2002)).  
      2) Step 3  
      A compound (17-4) may be produced from the compound (17-3) by the same production process as described in literature (for example, J. Org. Chem. 68, 4999 (2003) and Organic Process Research &amp; Development 7, 614 (2003)).  
      3) Step 4  
      A compound (17-5) may be produced from the compound (17-4) by the same production process as described in literature (for example, J. Am. Chem. Soc. 121, 975 (1999), Synth. Commun. 30, 341 (2000), Bioorg. Med. Chem. Lett. 9, 1625 (1999) and Sci. Pharm. 69, 161 (2001)).  
      4) Step 5  
      The compound (17-6) may be produced from the compound (17-5) by the same production process as described in the step 8 in the production process 1.  
      Production Process 18  
      A compound of the formula (18-5) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 190  and Y are as defined above; and R 250  is methyl, ethyl, propyl, 2-propyl or butyl. 
 
 1) Step 1 
 
      A compound (18-3) may be produced from a compound (15-2) by the same production process as described in literature (for example, J. Org. Chem. 47, 2117 (1982)).  
      2) Step 2  
      A compound (18-3) may be produced from the compound (18-2) by the same production process as described in literature (for example, J. Org. Chem. 61, 3200 (1996)).  
      3) Step 3  
      A compound (18-4) may be produced from the compound (18-3) by the same production process as described in the step 4 in the production process 17.  
      4) Step 4  
      The compound (18-5) may be produced from the compound (18-4) by the same production process as described in the step 8 in the production process 1.  
      Production Process 19  
      The compound (18-3) described in the production process 18 is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 190  and Y are as defined above; and R 260  is methyl, ethyl, propyl, 2-propyl or butyl. 
 
 1) Step 1 
 
      A compound (19-2) may be produced from a compound (15-2) by the same production process as described in literature (for example, Angew. Chem. Int Ed. Engl. 25, 508 (1986), Tetrahedron Lett. 31, 5877 (1990) and J. Org. Chem. 66, 9033 (2001)).  
      2) Steps 2 to 3  
      The compound (18-3) may be produced from the compound (19-2) by the same production process as described, for example, in Jikken Kagaku Koza (Experimental Chemistry) Vols. 20 to 23, Maruzen Co., Ltd. (published in 1992) and literature (for example, Tetrahedron Lett. 44, 5991 (2003)).  
      Production Process 20  
      The compound (1-8) described in the production process 1 may be produced also according to, for example, the following process:  
                 
 
 wherein m, n, R 7 , R 8 , R 20 , R 30  and Y are as defined above. 
 
 1) Step 1 
 
      A compound (20-1) may be produced from a compound (1-2) by the same process as in the step 2 described in the production process 1.  
      2) Step 2  
      The compound (1-8) may be produced from the compound (20-1) by the same process as in the step 1 described in the production process 1.  
      3) Step 3  
      It is also possible to produce the compound (1-8) from a compound (1-2) by carrying out the following reactions A and B.  
      A: The compound (1-2) is reacted with a compound (1-4), a compound (1-5), a compound (1-6) or a compound (1-7) in an inert solvent. The inert solvent includes, for example, alcohol solvents such as methanol, ethanol, 2-propanol, etc. The reaction temperature may be chosen in the range of about 0° C. to about 50° C.  
      B: A base and a compound (1-1) are added to the reaction mixture obtained in the item A and the reaction is carried out. The base includes, for example, organic bases such as imidazole, triethylamine, diisopropylethylamine, tributylamine, 1,5-diazabicyclo[4,3,0]non-5-ene, 1,4-diazabicyclo[2,2,2]octane, 1,8-diazabicyclo[5,4,0]undec-7-ene, 4-(dimethylamino)pyridine, picoline, etc. A preferable example thereof is triethylamine. The amount of the compound (1-1) used is usually chosen in the range of 3 to 10 equivalents per equivalent of the compound (1-2). The amount of the base used is usually chosen in the range of 5 to 15 equivalents per equivalent of the compound (1-2). The reaction temperature may be chosen in the range of about 50° C. to about 150° C.  
      Production Process 21  
      A compound of the formula (21-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 50 , R 170 , E 1  and Y a re as defined above; R 270  is “an optionally substituted alkenyl group”, “an optionally substituted aryl group” a or “an optionally substituted heteroaryl group”; and M 5  is trimethyltin, wherein R 280  is a hydrogen atom, methyl, ethyl or isopropyl. 
 
 1) Step 1 
 
      A compound (21-2) may be produced from a compound (14-2) by the same production process as described in literature (for example, Angew. Chem. Int Ed. Engl. 25, 508 (1986), Chem. Rev. 95, 2457 (1995), Org. Lett. 26, 4263 (2001), Tetrahedron 58, 10137 (2002) and J. Org. Chem. 66, 9033 (2001)).  
      2) Step 2  
      The compound (21-3) may be produced from the compound (21-2) by the same process as in the step 8 described in the production process 1.  
      Production Process 22  
      A compound of the formula (22-2) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 110  and Y are as defined above; and R 290  is “an optionally substituted aryl group” or “an optionally substituted heteroaryl group”. 
 
 1) Step 1 
 
      A compound (22-1) may be produced from a compound (9-5) by the same production process as described in literature (for example, Tetrahedron 55, 12757 (1999), Tetrahedron Lett. 43, 3091 (2002) and Chem. Pharm. Bull. 45, 719 (1997)).  
      2) Step 2  
      The compound (22-2) may be produced from the compound (22-1) by the same process as in the step 8 described in the production process 1.  
      Production Process 23  
      The compound (1-15) described in the production process 1 may be produced also according to, for example, the following production process:  
                 
 
 wherein R 6 , R 30 , R 40 , R 50  and Y are as defined above; and R 320  is benzyl, acetyl or benzoyl. 
 
 1) Step 1 
 
      A compound (23-2) may be produced from a compound (9-1) by the same process as in the step 1 described in the production process 6.  
      2) Step 2  
      A compound (23-3) may be produced from the compound (23-2) by the same production process as described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      3) Step 3  
      A compound (23-4) may be produced from the compound (23-3) by the same production process as described in literature (for example, Eur. J. Org. Chem. 45 (2001), Tetrahedron Letters 43, 8679 (2002), Synthesis 201 (2003), J. Am. Chem. Soc. 121, 6100 (1999), Tetrahedron Letters 33, 8145 (1992), Tetrahedron Letters 22, 4817 (1981) and J. Org. Chem. 45, 3131 (1980))  
      4) Step 4  
      The compound (1-15) may be produced from the compound (23-4) by the same production process as described in literature (for example, Org. React. 27, 345 (1982), Heterocycles 48, 2543 (1998) and Tetrahedron, 58, 6673 (2002)).  
      Production Process 24  
      A compound (1-5) may be produced according to, for example, the following process.  
                 
 
 wherein R 7 , R 30  and m are as defined above. 
 
 1) Step 1 
 
      The compound (1-5) may be produced from a compound (23-1) by the same production process as described in literature (for example, J. Org. Chem. 58, 879 (1993)).  
      Production Process 25  
      A compound (1-4) may be produced according to, for example, the following process.  
                 
 
 wherein R 7 , R 30  and m are as defined above; and R 330  is methyl or ethyl. 
 
 1) Step 1 
 
      A compound (25-2) may be produced by reacting a compound (25-1) with thionyl chloride or the like in an alcohol solvent. The alcohol solvent includes, for example, methanol and ethanol. The amount of thionyl chloride used is usually chosen in the range of 2 to 10 equivalents per equivalent of the compound (25-1). The reaction temperature may be chosen in the range of about −90° C. to about 30° C.  
      2) Step 2  
      A compound (25-3) may be produced by reacting the compound (25-2) with a base in water solvent. The base includes, for example, sodium hydrogencarbonate, potassium hydrogencarbonate, sodium carbonate and potassium carbonate. The reaction temperature may be chosen in the range of about 30° C. to about 100° C.  
      3) Step 3  
      A compound (25-4) may be produced from the compound (25-3) by the same process as that described in literature (for example, Protective Groups in Organic Synthesis 2nd Edition (John Wiley &amp; Sons, Inc.)), or the like.  
      4) Step 4  
      The compound (1-4) may be produced by reacting the compound (25-4) with a reducing agent in an inert solvent. The reducing agent includes, for example, aluminum lithium hydride, and diborane. The inert solvent includes, for example, tetrahydrofuran, 1,4-dioxane, mixed solvents thereof. When aluminum lithium hydride is used, the reaction temperature is chosen in the range of about −20° C. to about 40° C. When diborane is used, the reaction temperature is chosen in the range of about 50° C. to about 80° C.  
      Production Process 26  
      Examples of synthesis of compounds (1-5a) to (1-5j) as specific examples of the compound (1-5) are given below. The compounds (1-5a) to (1-5j) include pharmaceutically acceptable salts thereof.  
                                   Compound   Production process                                                    WO 02/48138 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     J. Org. Chem. 44, 2732 (1979) J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Produced starting from a compound (1-9f), according to, for example, the process described in J. Org. Chem. 44, 3872 (1979), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     Arch. Pharm., 322, 499 (1989) J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                  
 
      As hydrochloride of the compound (1-5e), a commercial one may also be used. It is also possible to synthesize the compound (1-5) from a substituted DL-ornithine by a well-known process. A specific example of the well-known process is the process described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
      Production Process 27  
      Examples of synthesis of compounds (1-4a) to (1-41) as specific examples of the compound (1-4) are given below. The compounds (1-4a) to (1-41) include pharmaceutically acceptable salts thereof.  
                                   Compound   Production Process                                                    WO 01/27082 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Int. J. Peptide Protein Res. 40, 119 (1992) WO 01/27082 J. Chem. Soc., Perking Trans. 1, 2233 (1999)                                     US 4413141 WO 01/27082 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Tetrahedron: Asymmetry 8, 327 (1997) WO 01/27082 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Tetrahedron: Asymmetry 11, 567 (2000) J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Chem. Eur. J. 6, 2830 (2000) WO 00/26332 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     JP-T-2002-525325 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Bull. Chem. Soc. Jpn. 53, 2605 (1980) J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Produced starting from a compound (1-4h), according to, for excample, the process described in J. Am. Chem. Soc. 80, 2584 (1958), J. Chem. Soc. PT1 499 (1972), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                  
 
 Production Process 28 
 
      Examples of synthesis of compounds (1-4j) to (1-4v) as specific examples of the compound (1-4) are given below. The compounds (1-4j) to (1-4v) include pharmaceutically acceptable salts thereof.  
                                   Compound   Production process                                                    Produced strating from compound (1-4f) in which R 30  is a hydrogen atom, according to, for example, the process described in J. Chem. Soc. Chem. Commun. 611 (1981), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     Produced starting from compound (1-4f) in which R 200  is a hydrogen atom, according to, for example, the process described in J. Chem. Soc. Chem. Commun. 611 (1981), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     Produced starting from a compound (1-4h), according to, for example, the process described in J. Org. Chem. 44, 3872 (1979), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     Produced starting from a compound (1-4e), according to, for example, the process described in J. Org. Chem. 44, 3872 (1979), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     Produced starting from a compound (1-4h), according to, for example, the process described in Bull. Chem. Soc. Jpn. 64, 2857 (1991), J. Chem. Soc., Perking Trans. 1, 2233 (1999).                                     Produced starting from a compound (1-4f) in which R 30  is a hydrogen atom, according to, for example, the process described in Tetrahedron Lett. 40, 5609(1999), J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     J. Med. Chem. 35, 833 (1992), R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 1989, J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                                     Produced starting from compound (1-4f) in which R 30  is a hydrogen atom, according to, for example, the process described in R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 1989, J. Chem. Soc., Perkin Trans. 1, 2233 (1999).                                     WO 02/068420 J. Chem. Soc., Perkin Trans. 1, 2233 (1999)                  
 
      Production Process 29  
      Examples of synthesis of compounds (1-4w) to (1-4dd) as specific examples of the compound (1-4) are given below. The compounds (1-4w) to (1-4dd) include pharmaceutically acceptable salts thereof.  
                                   Compound   Production process                                                                (1-4w): Y 4  = 2-CH 3 —C 6 H 5     Produced starting from a compound       (1-4x): Y 4  = 3-CH 3 —C 6 H 5     (1-4n),       (1-4y): Y 4  = 4-CH 3 —C 6 H 5     according to, for example, the process       (1-4z): Y 4  = 2-CH 3 —O—C 6 H 5     described in       (1-4aa): Y 4  = 3-CH 3 O—C 6 H 5     R. C. Ralock, “Comprehensive Organic       (1-4bb): Y 4  = 4-CH 3 O—C 6 H 5     transformation”,       (1-4cc): Y 4  = C 6 H 5     VCH publisher Inc., 1989,       (1-4dd): Y 4  = CH 2 C 6 H 5     J. Org.. Chem. 66, 3593 (2001),           J. Prakt. Chem. 342, 421 (2000),           Tetrahedron Lett. 36, 5611 (1994),           J. Org.. Chem. 53, 5143 (1988),           Bioorg. Med. Chem. Lett. 11, 1281           (2001),           J. Chem. Soc., Perkin Trans. 1, 2233           (1999).                  
 
      The compound (1-4) may be synthesized from a substituted D-ornithine by a well-known process. A specific example of the well-known process is the process described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
      Production Process 30  
      A compound (1-6) may be produced according to, for example, the following process.  
                 
 
 wherein R 8 , R 30  and n are as defined above. 
 
 1) Step 1 
 
      A compound (30-2) may be produced from a compound (30-1) by the same process as that described in literature (for example, Protective Groups in Organic Synthesis 2nd Edition (John Wiley &amp; Sons, Inc.)), or the like. The compound (30-1) may be produced by the same production process as described in literature (for example, J. Org. Chem. 50, 4154 (1985)).  
      2) Steps 2 to 4  
      The compound (1-6) may be produced from the compound (30-2) by the same process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
      Production Process 31  
      Examples of synthesis of compounds (1-6a) to (1-6aa) as specific examples of the compound (1-6) are given below. The compounds (1-6a) to (1-6aa) include pharmaceutically acceptable salts thereof. The compounds (1-6a) to (1-6aa) may be produced according to the processes described in literature (for example, WO01/74774, and R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
                 
                 
                 
                 
 
      Production Process 32  
      Examples of synthesis of compounds (1-6bb) to (1-6tt) as specific examples of the compound (1-6) are given below. The compounds (1-6bb) to (1-6tt) include pharmaceutically acceptable salts thereof. The compounds (1-6bb) to (1-6tt) may be produced according to the processes described in literature (for example, WO01/74774, and R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
                 
                 
                 
 
 Production Process 33 
 
      Compounds of the formula (33-4) and the formula (33-6) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 190 , R 215  and Y are as defined above; R 330 -Q 5  is “an optionally substituted aryloxy group”, “an optionally substituted arylthio group” or “an optionally substituted heteroaryloxy group”; R 330 -Q 6  is “an optionally substituted arylsulfonyl group”; E 3  is a chlorine atom or a bromine atom; and M 6  is lithium, sodium, potassium or cesium. 
 
 1) Step 1 
 
      A compound (33-1) may be produced from a compound (17-5) by the same production process as described in the step 1 in the production process 16.  
      2) Step 2  
      A compound (33-3) may be produced from the compound (33-1) by the same production process as described in the step 2 in the production process 16.  
      3) Step 3  
      The compound (33-4) may be produced from the compound (33-3) by the same production process as described in the step 8 in the production process 1.  
      4) Step 4  
      A compound (33-5) may be produced from the compound (33-3) by the same production process as described in the step 4 in the production process 16.  
      5) Step 5  
      The compound (33-6) may be produced from the compound (33-5) by the same production process as described in the step 8 in the production process 1.  
      Production Process 34  
      A compound of the formula (34-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein the compound (34-1) corresponds to the compound (16-1) described in the production process 16 or the compound (33-1) described in the production process 33; R 6 , R 30 , R 190  and Y are as defined above; R 350  is “an optionally substituted carbamoyl group”, “an optionally substituted aryl group”, “an optionally substituted alkoxycarbonyl group”, “an optionally substituted aryloxycarbonyl group”, “an optionally substituted aroyl group” or “an optionally substituted heteroaryl group”; R 340  is a hydrogen atom, a fluorine atom, methyl, ethyl or “an alkoxycarbonylmethyl group”; and E 4  is a chlorine atom or a bromine atom. 
 
 1) Step 1 
 
      A compound (34-2) may be produced from the compound (34-1) by the same production process as described in literature (for example, Chem. Rev. 103, 1979 (2003) and Chem. Rev. 103, 1875 (2003)).  
      2) Step 2  
      The compound (34-3) may be produced from the compound (34-2) by the same production process as described in the step 8 in the production process 1.  
      Production Process 35  
      A compound of the formula (35-4) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 190  and Y are as defined above; M 7  is trimethyltin, triethyltin, tributyltin, catechol borane, B(OR 360 ) 2  (wherein R 360  is a hydrogen atom, methyl, ethyl or isopropyl), or a group represented by the following formula (35-5):  
                 
 
 wherein R 370  is a hydrogen atom or methyl and mm is an integer of 0 or 1; the ring A is “an optionally substituted benzene ring, an optionally substituted cycloalkene ring or an optionally substituted 5-or 6-membered heteroaromatic ring”; and X 9  is an iodine atom, a chlorine atom or a bromine atom. 
 
 1) Step 1 
 
      A compound (35-2) may be produced from a compound (15-2) by the same production process as described in the step 1 in the production process 21.  
      As a compound (35-1), a commercial one may be used, or the compound (35-1) may be produced by the process described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
      2) Step 2  
      A compound (35-3) may be produced from the compound (35-2) by the same production process as described in literature (for example, Bioorg. Med. Chem. Lett. 13, 273 (2003), Synlett 231 (2002), J. Chem. Soc. Perkin Trans. 1, 733 (2002), Tetrahedron 52, 7525 (1996) and Chem. Rev. 103, 1875 (2003)).  
      3) Step 3  
      The compound (35-4) may be produced from the compound (35-3) by the same production process as described in the step 8 in the production process 1.  
      Production Process 36  
      Compounds of the formula (36-4) and the formula (36-7) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 20 , R 30 , R 6 , Y and A are as defined above; M 8  is trimethyltin, triethyltin, tributyltin, catechol borane, B(OR 390 ) 2  (wherein R 390  is a hydrogen atom, methyl, ethyl or isopropyl), or a group represented by the following formula (36-8):  
                 
 
 wherein R 400  is a hydrogen atom or methyl and nn is an integer of 0 or 1; R 380  is “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”; and X 10  is a leaving group (for example, a bromine atom, a chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy). 
 
 1) Step 1 
 
      A compound (36-2) may be produced from a compound (1-12) by the same production process as described in the step 1 in the production process 21.  
      As a compound (36-1), a commercial one may be used, or the compound (36-1) may be produced by the process described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989), Japanese Chemical Association, “Jikken Kagaku Koza (Experimental Chemistry)” Vol. 24, Maruzen Co., Ltd., J. Org. Chem. 67, 5394 (2002), J. Org. Chem. 65, 9268 (2000), Method of Element-Organic Chemistry, vol. 1, North-Holland (1967) and J. Am. Chem. Soc. 116, 11723 (1994)).  
      2) Step 2  
      A compound (36-3) may be produced by treating the compound (36-2) with a base in an inert solvent. The base includes, for example, alkoxy alkalis (sodium methoxide, sodium ethoxide and potassium t-butoxide). The amount of the base used is usually chosen in the range of 1 equivalent to large excess equivalents per equivalent of the compound (36-2). The inert solvent includes, for example, alcohol solvents (e.g. ethanol, methanol and 2-propanol), ether solvents (e.g. 1,4-dioxane), and mixed solvents thereof. The reaction temperature may be chosen in the range of about 50° C. to about 150° C.  
      3) Step 3  
      The compound (36-4) may be produced from the compound (36-3) by the same production process as described in the step 8 in the production process 1.  
      4) Step 4  
      A compound (36-6) may be produced from the compound (36-3) by the same production process as described in the step 1 in the production process 3.  
      5) Step 5  
      The compound (36-7) may be produced from the compound (36-6) by the same production process as described in the step 8 in the production process 1.  
      Production Process 37  
      The compounds (36-3) and (36-6) described in the production process 36 may be produced also according to, for example, the following production processes:  
                 
 
 wherein R 6 , R 30 , R 380 , Y, A and X 10  are as defined above. 
 
 1) Step 1 
 
      The following production process (A) or production process (B) may be adopted in the step 1.  
      Production process (A):  
      A compound (37-2) may be produced by condensing a compound (9-1) with a compound (37-1) in an inert solvent by the use of a dehydrating-condensation agent (e.g. dicyclohexylcarbodiimide or carbonyldiimidazole) optionally in the presence of an additive (e.g. 4-(dimethylamino)pyridine). The inert solvent includes, for example, ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, etc.; aprotic solvents such as N,N-dimethylformamide, etc.; and halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, etc. Mixed solvents of these solvents may also be used. A preferable example of the inert solvent is N,N-dimethylformamide. The reaction temperature is usually chosen in the range of about 0° C. to about 50° C.  
      Production process (B):  
      A compound (37-2) may be produced from a compound (9-1) by carrying out the following reactions (1) and (2).  
      (1) The compound (9-1) is reacted with oxalyl chloride or the like in an inert solvent in the presence or absence of an additive. The additive includes, for example, dimethylformamide. The amount of oxaly chloride used is usually chosen in the range of 1 to 3 equivalents (molar ratio). The inert solvent includes, for example, halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform, etc. The reaction temperature is usually chosen in the range of about −10° C. to about 50° C.  
      (2) The reaction solution obtained in the above item (1) is concentrated in the presence or absence of a hydrocarbon solvent such as toluene or benzene. The residue after the concentration is reacted with a compound (37-1) in an inert solvent in the presence of an organic base. The inert solvent includes, for example, halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform, etc.; and hydrocarbon solvents such as toluene, benzene, etc. The organic base includes, for example, N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), 1,4-diazabicyclo[5,4,0]undec-7-ene (DABCO), pyridine, dimethylaminopyridine and picoline. When these bases are liquid, they may be used also as a solvent.  
      A preferable example of the organic base is diisopropylethylamine. The amount of the compound (37-1) used is usually chosen in the range of 1 to 3 equivalents (molar ratio) per equivalent of the compound (9-1). The amount of the organic base used is usually chosen in the range of 1 to 20 equivalents (molar ratio) per equivalent of the compound (9-1). The reaction temperature is usually chosen in the range of about 10° C. to about 150° C.  
      2) Step 2  
      The compound (36-3) may be produced from the compound (37-2) by the same production process as described in literature (for example, Synthesis 444 (2001)).  
      3) Step 3  
      A compound (37-3) may be produced from the compound (37-2) by the same production process as described in the step 1 in the production process 3.  
      4) Step 4  
      The compound (36-6) may be produced from the compound (37-3) by the same production process as described in the above step 2.  
      Production Process 38  
      Compounds of the formula (38-3) and the formula (38-5) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 35 , Y and A are as defined above; R 420  is “a hydrogen atom”, “an optionally substituted alkyl group” or “an optionally substituted cycloalkyl group”; R 410  is “an alkyl group”; T A  is a single bond or an oxygen atom; and T B  is a single bond or an optionally substituted alkylene chain. 
 
 1) Step 1 
 
      A compound (38-2) may be produced from a compound (38-1) by the same production process as described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)). In such a reaction, a compound in which the protective group for the primary amino group in Y—NH 2  has been removed is produced in some cases. The primary amino group in Y—NH 2  may be protected again with the protective group (e.g. Boc or Cbz) by the same method as in the production process described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      2) Step 2  
      The compound (38-3) may be produced from the compound (38-2) by the same production process as described in the step 8 in the production process 1 or literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      3) Step 3  
      A compound (38-4) may be produced from the compound (38-2) by the same production process as described in the step 1 in the production process 3.  
      4) Step 4  
      The compound (38-5) may be produced from the compound (38-4) by the same production process as described in the above step 2.  
      5) Step 5  
      The compound (38-2) may be produced from the compound (38-3) by the same production process as described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      Production Process 39  
      Compounds of the formula (39-3) and the formula (39-5) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 420  Y, T A , T B  and A are as defined above; and R 440 R 450 NC(O) is “an optionally substituted carbamoyl group”. 
 
 1) Step 1 
 
      A compound (39-2) may be produced from a compound (38-2) by the same production process as described in the step 1 in the production process 6.  
      2) Step 2  
      The compound (39-3) may be produced from the compound (39-2) by the same production process as described in the step 2 in the production process 38.  
      3) Step 3  
      A compound (39-4) may be produced from a compound (39-2) in which each of R 440  and R 450  is a hydrogen atom, by the same production process as described in literature (for example, Synth Commun 32, 2535 (2002), and R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., (1989)).  
      4) Step 4  
      The compound (39-5) may be produced from the compound (39-4) by the same production process as described in the step 2 in the production process 38.  
      Production Process 40  
      A compound of the formula (40-3) as the compound of the formula (I), or a salt thereof is produced, for example, by the following process:  
                 
 
 wherein R 6 , R 30 , R 380 , R 420 , Y, X 10 , A, T A  and T B  are as defined above. 
 
 1) Step 1 
 
      A compound (40-1) may be produced from a compound (38-2) by carrying out the following reactions (1) and (2).  
      (1) The compound (38-2) is reacted with an alkyl chloroformate in an inert solvent in the presence of an organic base. The organic base includes, for example, N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), 1,4-diazabicyclo[5,4,0]undec-7-ene (DABCO), pyridine, dimethyl-aminopyridine and picoline. The amount of the organic base used is usually chosen in the range of 1 to 3 equivalents (molar ratio) per equivalent of the compound (38-2). The alkyl chloroformate includes, for example, isopropyl chloroformate, isobutyl chloroformate and n-butyl chloroformate. Preferable examples thereof are isopropyl chloroformate and isobutyl chloroformate. The amount of the alkyl chloroformate used is usually chosen in the range of 1 to 3 equivalents (molar ratio). The inert solvent includes, for example, ether solvents (e.g. diethyl ether, tetrahydrofuran and 1,4-dioxane). The reaction temperature is usually chosen in the range of about −10° C. to about 50° C.  
      (2) A reducing agent is added to the reaction solution obtained in the above item (1) and the reaction is carried out. The reducing agent includes, for example, hydrides such as lithium aluminum hydride, sodium borohydride, sodium cyanoborohydride, etc. A preferable example thereof is sodium borohydride. The amount of the reducing agent used is usually chosen in the range of 1 to 3 equivalents (molar ratio) per equivalent of the compound (38-2). The reaction temperature is usually chosen in the range of about −10° C. to about 50° C.  
      2) Step 2  
      A compound (40-2) may be produced from the compound (40-1) by the same production process as described in the step 1 in the production process 3.  
      3) Step 3  
      The compound (40-3) may be produced from the compound (40-2) by the same production process as described in the step 2 in the production process 38.  
      Production Process 41  
      Compounds of the formula (41-3), formula (41-5) and formula (41-7) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 35 , R 420 , Y, T A , T B  and A are as defined above; R 460  is “an alkyl group”; and R 470  is “an optionally substituted alkyl group”. 
 
 1) Step 1 
 
      A compound (41-1) may be produced from a compound (40-1) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989), Tetrahedron 59, 6739 (2003), Tetrahedron Letters 44, 2553 (2003), Synlett 1735 (2001) and J. Org. Chem. 66, 7907 (2001)).  
      2) Step 2  
      A compound (41-2) may be produced from the compound (41-1) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989), J. Org. Chem. 68, 6440 (2003), Eur. J. Med. Chem. 36, 673 (2001), Synth. Commun. 31, 89 (2001) and Synth. Commun. 26, 1921 (1996)).  
      3) Step 3  
      The compound (41-3) may be produced from the compound (41-2) by the same production process as described in the step 2 in the production process 38.  
      4) Step 4  
      A compound (41-4) may be produced from the compound (41-2) by the same production process as described in the step 9 in the production process 1.  
      5) Step 5  
      The compound (41-5) may be produced from the compound (41-4) by the same production process as described in the step 2 in the production process 38.  
      6) Step 6  
      A compound (41-6) may be produced from the compound (41-4) by the same production process as described in the step 3 in the production process 38.  
      7) Step 7  
      The compound (41-7) may be produced from the compound (41-6) by the same production process as described in the step 2 in the production process 38.  
      Production Process 42  
      Compounds of the formula (42-5), formula (42-10) and formula (42-9) as the compound of the formula (I), or salts thereof are produced, for example, by the following processes:  
                 
 
 wherein R 6 , R 30 , R 35 , R 420 , Y, T A , T B  and A are as defined above; R 500  is “an alkyl group”; each of R 480  and R 490  is “an optionally substituted alkyl group”; and M 9  is lithium, magnesium chloride or magnesium bromide. 
 
 1) Step 1 
 
      A compound (42-2) may be produced from a compound (41-1) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989)).  
      2) Step 2  
      A compound (42-3) may be produced from the compound (42-2) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989), Org. Lett. 4, 3935 (2002), Org. Lett. 5, 4425 (2003) and Tetrahedron Letters 44, 2553 (2003)).  
      3) Step 3  
      A compound (42-4) may be produced from the compound (42-3) by the same production process as described in literature (for example, R. C. Ralock, “Comprehensive Organic transformation”, VCH publisher Inc., 972-976 (1989), Tetrahedron 59, 9433 (2003) and Bioorg. Med. Chem. Lett. 13, 2227 (2003)).  
      4) Step 4  
      The compound (42-5) may be produced from the compound (42-4) by the same production process as described in the step 2 in the production process 38.  
      5) Step 5  
      A compound (42-6) may be produced from the compound (42-4) by the same production process as described in the step 9 in the production process 1.  
      6) Step 6  
      The compound (42-7) may be produced from the compound (42-6) by the same production process as described in the step 2 in the production process 38.  
      7) Step 7  
      A compound (42-9) may be produced from the compound (42-6) by the same production process as described in the step 3 in the production process 38.  
      8) Step 8  
      The compound (42-10) may be produced from the compound (42-9) by the same production process as described in the step 2 in the production process 38.  
      Production Process 43  
      A compound of the formula (IV) is produced, for example, by the following process:  
                 
 
 wherein R 1 , R 6 , R 30 , X 1  and A are as defined above. 
 
 1) Step 1 
 
      A compound (43-1) may be produced from the compound of the formula (IV) by the same production process as described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      2) Step 2  
      A compound (43-2) may be produced by hydrogenating the compound (43-1) in an inert solvent in the presence of a catalyst and in the presence or absence of an additive. The catalyst includes, for example, platinum catalysts such as platinum carbon, etc.; and palladium catalysts such as palladium carbon, palladium hydroxide carbon, etc. The additive includes ammonium formate and the like. The inert solvent includes, for example, alcohol solvents (e.g. ethanol, methanol and 2-propanol), ether solvents (tetrahydrofuran and 1,4-dioxane), and mixed solvents thereof. The reaction temperature may be chosen in the range of about 20° C. to about 100° C.  
      3) Step 3  
      The compound (43-1) may be produced from the compound (43-2) by the same production process as described in the step 3 in the production process 1.  
      4) Step 4  
      The compound of the formula (IV) may be produced from the compound (43-1) by the same production process as described in literature (for example, T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      In each of the production processes described above, when the starting compound in each reaction has a reactive group such as hydroxyl group, amino group or carboxyl group, the reactive group in a site other than a site where the reaction is desired is previously protected with a suitable protective group if necessary, and the protective group is removed after carrying out each reaction or after carrying out several reactions, whereby a desired compound may be obtained. As the protective group for protecting the hydroxyl group, amino group, carboxyl group or the like, conventional protective groups used in the field of organic synthetic chemistry may be used. The introduction and removal of such a protective group may be carried out according to a conventional method (for example, the method described in T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis” 2nd Edition, John Wiley &amp; Sons, Inc. (1991)).  
      For example, the protective group for the hydroxyl group includes tert-butyldimethylsilyl group, methoxymethyl group, tetrahydropyranyl group and the like. The protective group for the amino group includes tert-butoxycarbonyl group, benzyloxycarbonyl group and the like. Such a protective group for the hydroxyl group may be removed by reaction in a solvent such as aqueous methanol, aqueous ethanol or aqueous tetrahydrofuran in the presence of an acid such as hydrochloric acid, sulfuric acid or acetic acid. In the case of tert-butyldimethylsilyl group, it is also possible to carry out the removal in a solvent such as tetrahydrofuran in the presence of, for example, tetrabutylammonium fluoride. In the case of tert-butoxycarbonyl group, the protective group for the amino group may be removed, for example, by reaction in a solvent such as aqueous tetrahydrofuran, dichloromethane, chloroform or aqueous methanol in the presence of an acid such as hydrochloric acid or trifluoroacetic acid. In the case of benzyloxycarbonyl group, the removal may be carried out, for example, by reaction in a solvent such as acetic acid in the presence of an acid such as hydrobromic acid.  
      As a form in which the carboxyl group is protected, tert-butyl esters, orthoesters and acid amides are exemplified. Such a protective group is removed as follows. In the case of the tert-butyl esters, the removal is carried out, for example, by reaction in an aqueous solvent in the presence of hydrochloric acid. In the case of the orthoesters, the removal is carried out, for example, by treatment with an acid and then an alkali such as sodium hydroxide in a solvent such as aqueous methanol, aqueous tetrahydrofuran or aqueous 1,2-dimethoxyethane. In the case of the acid amides, the removal may be carried out, for example, by reaction in a solvent such as water, aqueous methanol or aqueous tetrahydrofuran in the presence of an acid such as hydrochloric acid or sulfuric acid.  
      The compound of the formula (I) includes those having a center of optical activity. The compound having a center of optical activity may be obtained as a racemic modification, or it may be obtained as an optically active substance when an optically active starting material is used. If necessary, the racemic modification obtained may be physically or chemically resolved into optical antipodes by a well-known method. Preferably, diastereomers are formed from the racemic modification by a reaction using a reagent for optical resolution. The diastereomers different in form may be resolved by a well-known method such as fractional crystallization.  
      The compound of the present invention or the prodrug thereof may be converted to a salt, for example, by mixing with a pharmaceutically acceptable acid in a solvent such as water, methanol, ethanol or acetone. The pharmaceutically acceptable acid includes, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.; and organic acids such as acetic acid, propionic acid, oxalic acid, succinic acid, lactic acid, malic acid, tartaric acid, citric acid, maleic acid, fumaric acid, methanesulfonic acid, p-toluenesulfonic acid, ascorbic acid, etc.  
      The agents of the present invention are expected to be usable for the treatment of various diseases because of their inhibitory effect on DPP-IV. The compounds disclosed in the present specification are useful for the suppression of postcibal hyperglycemia in a prediabetic, the treatment of non-insulin-dependent diabetes mellitus, the treatment of autoimmune diseases such as arthritis and articular rheumatism, the treatment of intestinal mucosa diseases, growth acceleration, the inhibition of rejection of a transplantate, the treatment of corpulence, the treatment of eating disorder, the treatment of HIV infection, the suppression of cancer metastasis, the treatment of prostatomegaly, the treatment of periodontitis, and the treatment of osteoporosis.  
      When used for the treatment, the present inventive compound may be administered as a pharmaceutical composition orally or parenterally (for example, by intravenous, subcutaneous or intramuscular injection, locally, intrarectally, percutaneously, or through nose). Compositions for the oral administration include, for example, tablets, capsules, pills, granules, powders, solutions and suspensions. Compositions for the parenteral administration include, for example, aqueous or oily preparations for injection, ointments, creams, lotions, aerosols, suppositories and patches. These pharmaceutical compositions are prepared by conventional techniques and may contain non-toxic and inactive carriers or excipients conventionally used in the field of formulation.  
      Although the dose is varied depending on the individual compounds, the disease, age, body weight and sex of a patient, symptom, administration route and the like, the present inventive compound is usually administered to an adult (body weight: 50 kg) in a dose of 0.1 to 1000 mg/day, preferably 1 to 300 mg/day in one portion or two or three portions a day. It is also possible to administer the present inventive compound at intervals of several days to several weeks.  
      The present inventive compound may be used in combination with drugs such as remedies for diabetes, remedies for diabetic complications, antilipemics, hypotensors, anti-corpulence drugs, diuretics, etc. (these drugs are hereinafter abbreviated as concomitant drugs) in order to enhance its effect. The timing of administration of the compound and the concomitant drugs is not limited. They may be administered to an object of administration either at the same time or at different times. The dose of the concomitant drugs may be properly chosen on the basis of a dose clinically employed. It is also possible to prepare a mixture of the compound and the concomitant drug(s). The proportions of the compound and the concomitant drug(s) may be properly chosen depending on an object of administration, administration route, a disease to be treated, symptom, a combination of the compound and the concomitant drug(s), and the like. For example, when the object of administration is a human being, the concomitant drug(s) is used in an amount of 0.01 to 100 parts by weight per part by weight of the compound.  
      The remedies for diabetes include insulin products (e.g. animal insulin products extracted from bovine or porcine pancreas; and human insulin products synthesized by a genetic engineering technique by the use of  Escherichia coli  or yeast), insulin resistance improving agents (e.g. pioglitazone or its hydrochloride, troglitazone, rosiglitazone or its maleate, GI-262570, JTT-501, MCC-555, YM-440, KRP-297 and CS-011), α-glucosidase inhibitors (e.g. voglibose, acarbose, miglitol and emiglitate), biguanide preparations (e.g. metformin), insulin secretion accelerators (e.g. sulfonylurea preparations such as tolbutamide, glibenclamide, gliclazide, chlorpropamide, tolazamide, acetohexamide, glyclopyramide, glimepiride, etc.; repaglinide, senaglinide, nateglinide and mitiglinide), GLP-1, GLP-1 analogs (exenatide, liraglutide, SUN-E7001, AVE010, BIM-51077 and CJC1131), protein tyrosine phosphatase inhibitors (e.g. vanadic acid), and β3 agonists (e.g. GW-427353B and N-5984).  
      The remedies for diabetic complications includes aldose reductase inhibitors (e.g. tolrestat, epalrestat, zenarestat, zopolrestat, minarestat, fidarestat, SK-860 and CT-112), neurotrophic factors (e.g. NGF, NT-3 and BDNF), PKC inhibitors (e.g. LY-333531), AGE inhibitors (e.g. ALT946, pimagezine, pyratoxathine and N-phenacylthiazolium bromide (ALT766)), active oxygen removers (e.g. thioctic acid), and cerebrovasodilators (e.g. tiapride and mexiletine). The antilipemics include HMG-CoA reductase inhibitors (e.g. pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, itavastatin, and their sodium salts), squalene synthetase inhibitors, ACAT inhibitors, and the like. The hypotensors include angiotensin converting enzyme inhibitors (e.g. captopril, enalapril, alacepril, delapril, lisinopril, imidapril, benazepril, cilazapril, temocapril and trandlapril), angiotensin II antagonists (e.g. candesartan cilexetil, losartan, eprosartan, valsartan, telmisartan, irbesartan and tasosartan), calcium antagonists (e.g. nicardipine hydrochloride, manidipine hydrochloride, nisoldipine, nitrandipine, nilvadipine and amlodipine), and the like.  
      The anti-corpulence drugs include, for example, central anti-corpulence drugs (e.g. phentermine, sibutramine, amfepramone, dexamphetamine, mazindol and SR-141716A), pancreas lipase inhibitors (e.g. orlistat), peptidergic anorexiants (e.g. leptin and CNTF (ciliary nerve trophic factor)) and cholecystokinin agonists (e.g. lintitript and FPL-15849). The diuretics include, for example, xanthine derivatives (e.g. sodium salicylate theobromine and potassium salicylate theobromine), thiazide preparations (e.g. ethiazide, cyclopenthiazide, trichlormethiazide, hydrochlorothiazide, hydroflumethiazide, benzylhydrochlorothiazide, penflutizide, polythiazide and methyclothiazide), anti-aldosterone preparations (e.g. spironolactone and triamteren), carbonate dehydratase inhibitors (e.g. acetazolamide), chlorobenzenesulfonamide preparations (e.g. chlorthalidone, mefruside and indapamide), azosamide, isosorbide, ethacrynic acid, piretanide, bumetanide and furosemide.  
      The concomitant drugs are preferably GLP-1, GLP-1 analogs, α-glucosidase inhibitors, biguanide preparations, insulin secretion accelerators, insulin resistance improving agents, and the like. The above-exemplified concomitant drugs may be used in combination of two or more thereof in proper proportions.  
      When the compound is used in combination with the concomitant drug(s), the amount of the drug(s) used may be reduced so as to be within a safe range in view of the side effects of the drug(s). In particular, the dose of the biguanide preparations may be reduced as compared with a conventional dose. Therefore, side effects causable by these drugs are safely preventable. In addition, the doses of the remedies for diabetic complications, antilipemics, hypotensors and the like may be reduced. As a result, side effects causable by these drugs are effectively preventable.  
     EXAMPLES  
      The present invention is more concretely illustrated below with reference examples, working examples and test examples, which should not be construed as limiting the scope of the invention. The nomenclature of compounds shown in the reference examples and working examples mentioned below is not always based on IUPAC.  
     Example 1  
     Methyl 2-[(3R)-3-aminopiperidin-1-yl]-7-chloro-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      The compound of Example 12 (12.2 mg) was dissolved in N,N-dimethylformamide (0.5 mL), followed by adding thereto N-chlorosuccinimide (8.0 mg), and the resulting mixture was stirred at room temperature for 3 hours. After the solvent was removed, the residue was purified by a preparative thin-layer silica gel chromatography (developing solvent: chloroform/methanol=10/1), followed by adding thereto 4N hydrochloric acid/1,4-dioxane, and the resulting mixture was concentrated to obtain the title compound (5.8 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.41 (dd, J=1.2, 7.8 Hz, 1H), 7.26-7.15 (m, 2H), 6.74 (dd, J=1.2, 7.6 Hz, 1H), 5.73 (d, J=17.0 Hz, 1H), 5.66 (d, J=17.0 Hz, 1H), 4.02 (s, 3H), 3.48-3.39 (m, 1H), 3.32-3.25 (m, 1H), 3.02-2.87 (m, 2H), 2.82-2.75 (m, 1H), 1.97-1.88 (m, 1H), 1.78-1.70 (m, 1H), 1.65-1.53 (m, 1H), 1.35-1.23 (m, 1H).  
      MS (ESI+) 450 (M + +1, 100%)  
     Example 2  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carbonitrile hydrochloride  
     
       
         
         
             
             
         
       
     
      Trifluoroacetic anhydride (851 μL) was added dropwise to a solution of the compound of Reference Example 52 (851 mg) in tetrahydrofuran (20 mL), and the resulting mixture was stirred at room temperature for 2 hours. After the reaction, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in methanol (20 mL). Potassium carbonate (323 mg) and water (0.3 mL) were added thereto and the resulting mixture was stirred at room temperature. After 1 hour, water was poured into the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1), whereby a product (645 mg) was isolated and purified as a white solid. To this product was added 4N hydrochloric acid/1,4-dioxane (10 mL), and the resulting mixture was stirred at 25° C. for 1 hour and concentrated under reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. To the concentrate was added 4N hydrochloric acid/1,4-dioxane (5 mL) and the resulting mixture was concentrated under reduced pressure to obtain the title compound (473 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.49-7.43 (m, 1H), 7.36 (s, 1H), 7.32-7.18 (m, 2H), 6.76-6.73(m, 1H), 5.74-5.64 (m, 2H), 3.68 (s, 3H), 3.68-3.63 (m, 1H), 3.48-3.38 (m, 1H), 3.25-3.14 (m, 2H), 3.00-2.89 (m, 1H), 2.12-2.03 (m, 1H), 1.82-1.70 (m, 1H), 1.69-1.55 (m, 2H).  
      MS (ESI+) 397 (M + +1, 100%).  
     Example 3  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-(carboxymethyl)-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one hydrochloride  
     
       
         
         
             
             
         
       
     
      The compound of Example 37 (25 mg) was dissolved in 6N hydrochloric acid (2 mL) and the resulting solution was stirred with heating at 100° C. for 8 hours. The reaction solution was cooled to 25° C. and then concentrated under reduced pressure, and toluene was added thereto, followed by azeotropic distillation, whereby the title compound (26 mg) was obtained as a light-yellow solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.51-7.49 (m, 1H), 7.37-7.28 (m, 2H), 7.10-7.07 (m, 1H), 6.71(s, 1H), 5.74-5.67 (m, 2H), 3.98 (s, 2H), 3.86-3.83 (m, 1H), 3.52 (s, 3H), 3.52-3.11 (m, 4H), 2.14-2.08 (m, 1H), 1.86-1.65 (m, 3H).  
      MS (ESI+) 430 (M + +1, 100%).  
     Example 4  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      A 4N hydrochloric acid/1,4-dioxane solution (3 mL) was added to the compound of Reference Example 7 (49 mg) and the resulting mixture was stirred at 25° C. for 2 hours. Water was poured into the reaction solution and the aqueous layer was washed with chloroform. Then, the aqueous layer was adjusted to pH 8 with a 4N aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (26 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.41-7.38 (m, 1H), 7.22-7.13 (m, 2H), 7.09 (d, J=7.2 Hz, 1H), 6.75-6.73 (m, 1H), 6.59 (d, J=7.2 Hz, 1H), 5.70 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 3.57 (s, 3H), 3.35-3.31 (m, 1H), 3.22-3.19 (m, 1H), 2.93-2.88 (m, 2H), 2.71-2.66 (m, 1H), 1.85-1.22 (m, 4H).  
      MS (ESI+) 372 (M + +1, 100%).  
      The compounds of Examples 5 to 11 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Example 4.  
                                                                                                                  Reference example                       number for starting       Example number   R 1     R 2     R 6     material                                       Example 5   Me   MeO(O)C                         Reference Example 13               Example 6   H   Et 2 N(CH 2 ) 3 O(O)C                         Reference Example 14               Example 7                         H                         Reference Example 22               Example 8   EtOC(O)CH 2     H                         Reference Example 23               Example 9                         H                         Reference Example 24               Example 10                         H                         Reference Example 25               Example 11   Me   H                         Reference Example 1                  
 
     Example 5  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.38 (m, 1H), 7.35 (s, 1H), 7.27-7.12 (m, 2H), 6.73-6.70 (m, 1H), 5.71 (d, J=17.0 Hz, 1H), 5.65 (d, J=17.0 Hz, 1H), 3.92 (s, 3H), 3.73 (s, 3H), 3.39-3.31 (m, 1H), 3.25-3.16 (m, 1H), 2.97-2.87 (m, 2H), 2.75-2.65 (m, 1H), 1.95-1.85 (m, 1H), 1.78-1.66 (m, 1H), 1.34-1.23 (m, 2H).  
      MS (ESI+) 430 (M + +1, 100%).  
     Example 6  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (s, 1H), 7.42-7.39 (m, 1H), 7.25-7.14 (m, 2H), 6.78-6.76 (m, 1H), 5.72 (d, J=17.0 Hz, 1H), 5.66 (d, J=17.0 Hz, 1H), 4.41 (t, J=6.4 Hz, 2H), 3.39-3.31 (m, 1H), 3.26-3.17 (m, 1H), 2.94-2.84 (m, 2H), 2.73-2.65 (m, 1H), 2.60-2.48 (m, 6H), 1.95-1.85 (m, 2H), 1.80-1.59 (m, 2H), 1.31-1.19 (m, 2H), 1.02 (t, J=7.1 Hz, 6H).  
      MS (ESI+) 515 (M + +1, 100%).  
     Example 7  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.02-7.98 (m, 2H), 7.64-7.57 (m, 1H), 7.50-7.44 (m, 2H), 7.38-7.34 (m, 1H), 7.20-7.13 (m, 2H), 7.03 (d, J=7.2 Hz, 1H), 6.81-6.78 (m, 1H), 6.69 (d, J=7.2 Hz, 1H), 5.67 (d, J=17.0 Hz, 1H), 5.62 (d, J=17.0 Hz, 1H), 5.42 (s, 2H), 3.38-3.32 (m, 1H), 3.24-3.16 (m, 1H), 2.95-2.84 (m, 2H), 2.72-2.64 (m, 1H), 1.94-1.83 (m, 1H), 1.76-1.65 (m, 1H), 1.33-1.19 (m, 2H).  
      MS (ESI+) 476 (M + +1, 100%).  
     Example 8  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.22-7.10 (m, 2H), 7.02 (d, J=7.3 Hz, 1H), 6.78-6.72 (m, 1H), 6.64 (d, J=7.3 Hz, 1H), 5.71-5.59 (m, 2H), 4.67 (s, 2H), 4.22 (q, J=7.2 Hz, 2H), 3.39-3.31 (m, 1H), 3.21-3.14 (m, 1H), 3.02-2.84 (m, 2H), 2.82-2.72 (m, 1H), 1.87-1.76 (m, 2H), 1.64-1.53 (m, 1H), 1.40-1.28 (m, 1H), 1.25 (t, J=7.2 Hz, 3H).  
      MS (ESI+) 444 (M + +1, 100%).  
     Example 9  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.95-7.84 (m, 1H), 7.66-7.55 (m, 1H), 7.49-7.35 (m, 1H), 7.30-6.89 (m, 5H), 6.76-6.71 (m, 1H), 6.69-6.59 (m, 1H), 5.70-5.52 (m, 2H), 5.34 (s, 2H), 3.95(s, 3H), 3.41-3.30 (m, 1H), 3.23-3.10 (m, 1H), 3.09-2.73 (m, 3H), 1.95-1.81 (m, 1H), 1.78-1.50 (m, 2H), 1.48-1.30 (m, 1H).  
      MS (ESI+) 506 (M + +1, 100%).  
     Example 10  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.61-7.54 (m, 1H), 7.53-7.45 (m, 1H), 7.42-7.32 (m, 2H), 7.21-7.08 (m, 3H), 7.02 (d, J=7.2 Hz, 1H), 6.81-6.75 (m, 1H), 6.69 (d, J=7.2 Hz, 1H), 5.69-5.58 (m, 2H), 5.40 (s, 2H), 3.83 (s, 3H), 3.38-3.30 (m, 1H), 3.23-3.14 (m, 1H), 3.00-2.84 (m, 2H), 2.78-2.68 (m, 1H), 1.95-1.81 (m, 1H), 1.75-1.66 (m, 2H), 1.34-1.22 (m, 1H).  
      MS (ESI+) 506 (M + +1, 100%).  
     Example 11  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.41-7.34 (m, 1H), 7.20 (d, J=7.2 Hz, 1H), 6.94-6.87 (m, 1H), 6.59 (d, J=7.2 Hz, 1H), 6.51-6.41 (m, 1H), 5.66-5.56 (m, 2H), 3.57 (s, 3H), 3.36-3.28(m, 1H), 3.22-3.12 (m, 1H), 2.98-2.84 (m, 2H), 2.72-2.63 (m, 1H), 1.96-1.87 (m, 1H), 1.78-1.68 (m, 1H), 1.65-1.53 (m, 1H), 1.30-1.20 (m, 1H).  
      MS (ESI+) 392 (M + +3, 100%).  
     Example 12  
     Methyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      A 4N hydrochloric acid/1,4-dioxane solution (10 mL) was added to the compound of Reference Example 16 (1.01 g) and the resulting mixture was stirred at 25° C. for 1 hour. After the reaction solution was concentrated under reduced pressure, toluene was added thereto, followed by azeotropic distillation. Thus, 1,4-dioxane was completely removed to obtain the title compound (870 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.50-7.45 (m, 1H), 7.39 (s, 1H), 7.36-7.24 (m, 2H), 6.99-6.87 (m, 1H), 5.73 (s, 2H), 3.97 (s, 3H), 3.81-3.70 (m, 1H), 3.49-3.38 (m, 1H), 3.34-3.18 (m, 2H), 3.09-2.97 (m, 1H), 2.17-2.05 (m, 1H), 1.89-1.75 (m, 1H), 1.72-1.58 (m, 2H).  
      MS (ESI+) 416 (M + +1, 100%).  
      The compounds of Examples 13 to 43 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Example 12.  
                                                                                                          Reference                   example                   number for       Example           starting       number   R 1     R 2     material               Example 13   H   CO 2 H   Reference                   Example 17       Example 14   H   EtO(O)C   Reference                   Example 48       Example 15   Me   Me 2 N(O)C   Reference                   Example 54       Example 16   Me   CO 2 H   Reference                   Example 47       Example 17   H   Me 2 CHO(O)C   Reference                   Example 49       Example 18   H   BnO(O)C   Reference                   Example 50       Example 19   H   H 2 N(O)C   Reference                   Example 51               Example 20   H                         Reference Example 15                  
 
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 Reference example 
               
               
                   
                   
                   
                   
                 number for starting 
               
               
                 Example number 
                 R 1   
                 R 2   
                 R 6   
                 material 
               
               
                   
               
               
                   
                   
                   
                   
                   
               
               
                 Example 21 
                 Me 
                 Me(O)C 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 32 
               
               
                   
               
               
                 Example 22 
                 Me 
                 Ph(O)C 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 33 
               
               
                   
               
               
                 Example 23 
                 HOC(O)CH 2   
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 28 
               
               
                   
               
               
                 Example 24 
                 H 
                 MeO(O)C 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 55 
               
               
                   
               
               
                 Example 25 
                 Et 
                 HOCH 2   
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 64 
               
               
                   
               
               
                 Example 26 
                 H 
                 CO 2 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 56 
               
               
                   
               
               
                 Example 27 
                 H 
                 MeO(O)C 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 57 
               
               
                   
               
               
                 Example 28 
                 H 
                 CO 2 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 65 
               
               
                   
               
               
                 Example 29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 66 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
            
               
                   
               
               
                   
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Reference example 
               
               
                   
                   
                   
                 number for starting 
               
               
                 Example number 
                 R 1   
                 R 2   
                 material 
               
               
                   
               
               
                   
                   
                   
                   
               
               
                 Example 30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 Reference Example 67 
               
               
                   
               
               
                 Example 31 
                 PhC(O)CH(Me) 
                 H 
                 Reference Example 26 
               
               
                 Example 32 
                 PhO(CH 2 ) 2   
                 H 
                 Reference Example 27 
               
               
                 Example 33 
                 Ph 
                 H 
                 Reference Example 68 
               
               
                   
               
               
                 Example 34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 H 
                 Reference Example 69 
               
               
                   
               
               
                 Example 35 
                 Me 
                 CH 2 OPh 
                 Reference Example 70 
               
               
                   
               
               
                 Example 36 
                 Me 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 71 
               
               
                   
               
               
                 Example 37 
                 Me 
                 NCCH 2   
                 Reference Example 72 
               
               
                   
               
               
                 Example 38 
                 Me 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 34 
               
               
                   
               
               
                 Example 39 
                 Me 
                 PhCH 2 (O)C 
                 Reference Example 35 
               
               
                   
               
               
                 Example 40 
                 Me 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 36 
               
               
                   
               
               
                 Example 41 
                 Me 
                 i-Pr(O)C 
                 Reference Example 37 
               
               
                   
               
               
                 Example 42 
                 Me 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Reference Example 38 
               
               
                   
               
               
                 Example 43 
                 Me 
                 CHO 
                 Reference Example 39 
               
               
                   
               
            
           
         
       
     
     Example 13  
      1H NMR (400 MHz, CD 3 OD) δ 7.51-7.45 (m, 1H), 7.35 (s, 1H), 7.34-7.22 (m, 2H), 7.03-6.87 (m, 1H), 5.74 (s, 2H), 3.86-3.70 (m, 1H), 3.51-3.39 (m, 1H), 3.37-3.18 (m, 2H), 3.13-2.95 (m, 1H), 2.16-2.05 (m, 1H), 1.89-1.77 (m, 1H), 1.75-1.55 (m, 2H).  
      MS (ESI+) 402 (M + +1, 100%).  
     Example 14  
       1 H NMR (400 MHz, CD 3 OD) δ 7.48-7.40 (m, 1H), 7.39 (s, 1H), 7.32-7.18 (m, 2H), 6.81-6.73 (m, 1H), 5.76-5.70 (m, 2H), 4.42 (q, J=7.1 Hz, 2H), 3.71-3.63 (m, 1H), 3.50-3.37 (m, 1H), 3.23-3.08 (m, 2H), 3.00-2.89 (m, 1H), 2.13-2.02 (m, 1H), 1.86-1.71 (m, 1H), 1.70-1.51 (m, 2H) 1.40 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 430 (M + +1, 100%).  
     Example 15  
       1 H NMR (400 MHz, CD 3 OD) δ 7.45-7.38 (m, 1H), 7.28-7.15 (m, 2H), 6.97-6.90 (m, 1H), 6.62(s, 1H), 5.63 (s, 2H), 3.76-3.68 (m, 1H), 3.42-3.34 (m, 1H), 3.34 (s, 3H), 3.28-3.15 (m, 2H), 3.04 (s, 3H), 3.04-2.97 (m, 1H), 2.94 (s, 3H), 2.08-1.96 (m, 1H), 1.81-1.70 (m, 1H), 1.66-1.54 (m, 2H).  
      MS (ESI+) 443 (M + +1, 100%).  
     Example 16  
       1 H NMR (400 MHz, CD 3 OD) δ 7.49-7.47 (m, 1H), 7.33 (s, 1H), 7.33-7.23 (m, 2H), 6.90-6.87 (m, 1H), 5.72 (s, 2H), 3.79-3.71 (m, 1H), 3.70 (s, 3H), 3.50-3.41 (m, 1H), 3.33-3.20 (m, 2H), 3.08-2.99 (m, 1H), 2.14-2.05 (m, 1H), 1.89-1.78 (m, 1H), 1.74-1.55 (m, 2H).  
      MS (ESI+) 416 (M + +1, 100%).  
     Example 17  
       1 H NMR (400 MHz, CD 3 OD) δ 7.52-7.45 (m, 1H), 7.35 (s, 1H), 7.37-7.27 (m, 2H), 7.15-7.02 (m, 1H), 5.76 (s, 2H), 5.30-5.22 (m, 1H), 3.99-3.83 (m, 1H), 3.53-3.32 (m, 3H), 3.23-3.08 (m, 1H), 2.20-2.08 (m, 1H), 1.94-1.80 (m, 1H), 1.75-1.61 (m, 2H), 1.40 (s, 3H), 1.38 (s, 3H).  
      MS (ESI+) 444 (M + +1, 100%).  
     Example 18  
      MS (ESI+) 492 (M + +1, 100%).  
     Example 19  
       1 H NMR (400 MHz, CD 3 OD) δ 7.43-7.38 (m, 1H), 7.30-7.15 (m, 2H), 7.27 (s, 1H), 6.89-6.81 (m, 1H), 5.64 (s, 2H), 3.73-3.63 (m, 1H), 3.51-3.39 (m, 1H), 3.37-3.13 (m, 2H), 3.04-2.92 (m, 1H), 2.08-1.96 (m, 1H), 1.81-1.69 (m, 1H), 1.65-1.49 (m, 2H).  
      MS (ESI+) 401 (M + +1, 100%).  
     Example 20  
       1 H NMR (400 MHz, CD 3 OD) δ 7.54 (s, 1H), 7.53-7.46 (m, 1H), 7.38-7.25 (m, 2H), 7.00-6.94 (m, 1H), 5.73 (s, 2H), 4.79-4.71 (m, 2H), 4.09-3.97 (m, 2H), 3.95-3.77 (m, 3H), 3.74-3.55 (m, 5H), 3.53-3.41 (m, 1H), 3.38-3.06 (m, 4H), 2.17-2.05 (m, 1H), 1.91-1.79 (m, 1H), 1.75-1.61 (m, 2H).  
      MS (ESI+) 515 (M + +1, 100%).  
     Example 21  
       1 H NMR (400 MHz, CD 3 OD) δ 7.50-7.47 (m, 1H), 7.33 (s, 1H), 7.33-7.28 (m, 1H), 7.26-7.22 (m, 1H), 6.83-6.81 (m, 1H), 5.71 (s, 2H), 3.75-3.66 (m, 1H), 3.56 (s, 3H), 3.50-3.40 (m, 1H), 3.31-3.20 (m, 2H), 3.04-2.93 (m, 1H), 2.63 (s, 3H), 2.17-2.05 (m, 1H), 1.88-1.74 (m, 1H), 1.71-1.55 (m, 2H).  
      MS (ESI+) 414 (M + +1, 100%).  
     Example 22  
       1 H NMR (400 MHz, CD 3 OD) δ 7.98-7.93 (m, 2H), 7.78-7.70 (m, 1H), 7.62-7.54 (m, 2H), 7.51-7.45 (m, 1H), 7.38-7.23 (m, 2H), 6.95-6.83 (m, 1H) 6.79(s, 1H), 5.74 (s, 2H), 3.78-3.62 (m, 1H), 3.48 (s, 3H), 3.48-3.39 (m, 1H), 3.38-3.18 (m, 2H), 3.09-2.95 (m, 1H), 2.17-2.04 (m, 1H), 1.87-1.75 (m, 1H), 1.74-1.53 (m, 2H).  
      MS (ESI+) 476 (M + +1, 100%).  
     Example 23  
       1 H NMR (400 MHz, CD 3 OD) δ 7.56-7.59 (m, 1H), 7.48 (d, J=7.3 Hz, 1H), 7.37-7.24 (m, 2H), 7.07-7.00 (m, 1H), 6.70(d, J=7.3 Hz, 1H), 5.68 (s, 2H), 4.76 (s, 2H), 3.88-3.79 (m, 1H), 3.50-3.42 (m, 1H), 3.39-3.23 (m, 2H), 3.17-3.07 (m, 1H), 2.17-2.08 (m, 1H), 1.91-1.79(m, 1H), 1.74-1.61 (m, 2H).  
      MS (ESI+) 416 (M + +1, 100%).  
     Example 24  
       1 H NMR (400 MHz, CD 3 OD) δ 7.53-7.46 (m, 1H), 7.39 (s, 1H), 7.14-7.03 (m, 1H), 6.78-6.63 (m, 1H), 5.66 (s, 2H), 3.96 (s, 3H), 3.80-3.69 (m, 1H), 3.55-3.42 (m, 1H), 3.34-3.21 (m, 2H), 3.13-3.01 (m, 1H), 2.17-2.08 (m, 1H), 1.93-1.80 (m, 1H), 1.78-1.51 (m, 2H).  
      MS (ESI+) 434 (M + +1, 100%).  
     Example 25  
       1 H NMR (400 MHz, CD 3 OD) δ 7.53-7.48 (m, 1H), 7.40-7.28 (m, 2H), 7.18-7.11 (m, 1H), 6.83 (s, 1H), 5.79-5.69 (m, 2H), 4.66 (s, 2H), 3.97-3.90 (m, 1H), 3.65 (s, 3H), 3.51-3.37 (m, 3H), 3.22-3.12 (m, 1H), 2.19-2.09 (m, 1H), 1.92-1.80 (m, 1H), 1.76-1.64 (m, 2H).  
      MS (ESI+) 402 (M + +1, 100%).  
     Example 26  
       1 H NMR (400 MHz, CD 3 OD) δ 7.56-7.48 (m, 1H), 7.38 (s, 1H), 7.16-7.09 (m, 1H), 6.91-6.81 (m, 1H), 5.67 (s, 2H), 3.86-3.78 (m, 1H), 3.59-3.49 (m, 1H), 3.40-3.29 (m, 2H), 3.20-3.08 (m, 1H), 2.19-2.10 (m, 1H), 1.94-1.82 (m, 1H), 1.79-1.64 (m, 2H).  
      MS (ESI+) 420 (M + +1, 100%).  
     Example 27  
       1 H NMR (400 MHz, CD 3 OD) δ 7.32 (s, 1H), 5.44-5.39 (m, 1H), 5.07-5.00 (m, 2H), 3.96 (s, 3H), 3.87-3.75 (m, 1H), 3.62-3.50 (m, 2H), 3.37-3.16 (m, 2H), 2.28-2.13 (m, 1H), 2.07-1.93 (m, 1H), 1.91-1.69 (m, 2H), 1.82 (s, 3H), 1.76 (s, 3H).  
      MS (ESI+) 360 (M + +1, 100%).  
     Example 28  
       1 H NMR (400 MHz, CD 3 OD) δ 7.32 (s, 1H), 5.48-5.39 (m, 1H), 5.10-4.98 (m, 2H), 3.92-3.75(m, 1H), 3.64-3.48 (m, 2H), 3.39-3.13 (m, 2H), 2.25-2.13 (m, 1H), 2.07-1.93 (m, 1H), 1.91-1.64 (m, 2H), 1.82 (s, 3H), 1.77 (s, 3H).  
      MS (ESI+) 346 (M + +1, 100%).  
     Example 29  
       1 H NMR (400 MHz, CD 3 OD) δ 7.50-7.35 (m, 2H), 7.33-7.13 (m, 4H), 7.05-6.85 (m, 3H), 6.67-6.69 (m, 1H), 5.71 (s, 2H), 3.81 (s, 3H), 3.79-3.65 (m, 1H), 3.51-3.36 (m, 1H), 3.35-3.26 (m, 2H), 3.11-2.95 (m, 1H), 2.17-2.03 (m, 1H), 1.90-1.77 (m, 1H), 1.75-1.55 (m, 2H).  
      MS (ESI+) 464 (M + +1, 100%).  
     Example 30  
       1 H NMR (400 MHz, CD 3 OD) δ 7.56-7.42 (m, 3H), 7.31-7.15 (m, 5H), 6.97-6.91 (m, 1H), 6.77(d, J=7.3 Hz, 1H), 5.69 (s, 2H), 3.80-3.68 (m, 1H), 3.49-3.39 (m, 1H), 3.35-3.20 (m, 2H), 3.05-2.95 (m, 1H), 2.15-2.05 (m, 1H), 1.89-1.75 (m, 1H), 1.74-1.55 (m, 2H).  
      MS (ESI+) 452 (M + +1, 100%).  
     Example 31  
       1 H NMR (400 MHz, CD 3 OD) δ 7.91-7.84 (m, 2H), 7.61-7.51 (m, 2H), 7.49-7.38 (m, 3H), 7.35-7.28 (m, 1H), 7.24-7.16 (m, 1H), 6.82-6.75 (m, 1H), 6.71 (d, J=7.4 Hz, 1H), 6.38-6.28 (m, 1H), 5.72-5.58 (m, 2H), 3.76-3.68 (m, 1H), 3.49-3.35 (m, 1H), 3.32-3.16 (m, 2H), 3.08-2.95 (m, 1H), 2.13-2.04 (m, 1H), 1.89-1.75 (m, 1H), 1.70-1.54 (m, 2H), 1.64-1.62 (m, 3H).  
      MS (ESI+) 490 (M + +1, 100%).  
     Example 32  
       1 H NMR (400 MHz, CD 3 OD) δ 7.77-7.68 (m, 1H), 7.51-7.45 (m, 1H), 7.38-7.16 (m, 4H), 7.05-6.97 (m, 1H), 6.92-6.77 (m, 3H), 6.66 (d, J=7.3 Hz, 1H), 5.72 (s, 2H), 4.40 (t, J=4.9 Hz, 2H), 4.21 (t, J=4.9 Hz, 2H), 3.85-3.74 (m, 1H), 3.50-3.42 (m, 1H), 3.38-3.22 (m, 2H), 3.14-3.03 (m, 1H), 2.17-2.05 (m, 1H), 1.90-1.78 (m, 1H), 1.76-1.55 (m, 2H).  
      MS (ESI+) 478 (M + +1, 100%).  
     Example 33  
       1 H NMR (400 MHz, CD 3 OD) δ 7.55-7.40 (m, 5H), 7.36-7.33 (m, 2H), 7.27-7.18 (m, 2H), 6.86-6.84 (m, 1H), 6.75 (d, J=7.3 Hz, 1H), 5.69 (s, 2H), 3.50-3.15 (m, 4H), 3.05-2.95 (m, 1H), 2.15-2.08 (m, 1H), 1.87-1.73 (m, 1H), 1.72-1.53 (m, 2H).  
      MS (ESI+) 434 (M + +1, 100%).  
     Example 34  
       1 H NMR (400 MHz, CD 3 OD) δ 7.72-7.54 (m, 1H), 7.48-7.42 (m, 1H), 7.41-7.18 (m, 6H), 7.10-7.00 (m, 1H), 6.79-6.77 (m, 1H), 5.71 (s, 2H), 3.90-3.75 (m, 1H), 3.55-3.42 (m, 1H), 3.40-3.22 (m, 2H), 3.18-3.05 (m, 1H), 2.18-2.05 (m, 1H), 1.90-1.75 (m, 1H), 1.7-1.52 (m, 2H).  
      MS (ESI+) 452 (M + +1, 100%).  
     Example 35  
       1 H NMR (400 MHz, CD 3 OD) δ 7.51-7.46 (m, 1H), 7.38-7.25 (m, 4H), 7.10-6.97 (m, 3H), 6.89-6.86 (m, 2H), 5.71 (s, 2H), 5.17 (s, 2H), 3.77-3.68 (m, 1H), 3.63 (s, 3H), 3.50-3.39 (m, 1H), 3.37-3.21 (m, 2H), 3.08-2.98 (m, 1H), 2.14-2.05 (m, 1H), 1.90-1.80 (m, 1H), 1.85-1.72 (m, 2H).  
      MS (ESI+) 478 (M + +1, 100%).  
     Example 36  
       1 H NMR (400 MHz, CD 3 OD) δ 7.49-7.46 (m, 1H), 7.38-7.23 (m, 3H), 6.87 (s, 1H), 6.87-6.85(m, 1H), 6.69-6.57 (m, 3H), 5.71 (s, 2H), 5.16 (s, 2H), 3.77 (s, 3H), 3.60 (s, 3H), 3.73-3.12 (m, 4H), 3.10-3.00 (m, 1H), 2.18-2.10 (m, 1H), 1.91-1.80 (m, 1H), 1.81-1.61 (m, 2H).  
      MS (ESI+) 508 (M + +1, 100%).  
     Example 37  
       1 H NMR (400 MHz, CD 3 OD) δ 7.51-7.45 (m, 1H), 7.35-7.24 (m, 2H), 6.96-6.94 (m, 1H), 6.86(s, 1H), 5.70 (s, 2H), 4.23 (s, 2H), 3.82-3.56 (m, 3H), 3.57 (s, 3H), 3.49-3.41 (m, 1H), 3.12-3.02 (m, 1H), 2.17-2.07 (m, 1H), 1.88-1.62 (m, 3H).  
      MS (ESI+) 411 (M + +1, 100%).  
     Example 38  
       1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 8.21-8.18 (m, 3H), 7.60 (s, 1H), 7.53-7.50 (m, 1H), 7.32-7.24 (m, 3H), 6.89-6.85 (m, 3H), 6.64 (d, J=6.4 Hz, 1H), 5.59 (s, 2H), 4.35 (s, 2H), 3.74 (s, 3H), 3.62-3.58 (m, 1H), 3.34 (s, 3H), 3.34-3.32 (m, 1H), 3.16-3.05 (m, 2H), 2.85-2.80 (m, 1H), 1.94-1.91 (m, 1H), 1.75-1.71 (m, 1H), 1.56-1.49 (m, 2H).  
      MS (ESI+) 520 (M + +1, 100%).  
     Example 39  
       1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 8.16-8.10 (m, 3H), 7.60 (s, 1H), 7.52-7.50 (m, 2H), 7.36-7.24 (m, 7H), 6.65-6.62 (m, 1H), 5.58 (s, 2H), 4.38 (s, 2H), 3.45-3.40 (m, 1H), 3.32 (s, 3H), 3.14-3.07 (m, 2H), 2.83-2.80 (m, 1H), 1.92-1.90 (m, 1H), 1.75-1.72 (m, 1H), 1.53-1.48 (m, 2H).  
      MS (ESI+) 490 (M + +1, 100%).  
     Example 40  
       1 H NMR (400 MHz, DMSO-d 6 ) δ ppm 8.09-8.03 (m, 3H), 7.55-7.53 (m, 2H), 7.46-7.43 (m, 2H), 7.36-7.28 (m, 3H), 6.76 (s, 1H), 6.73-6.71 (m, 1H), 5.62 (s, 2H), 3.85 (s, 3H), 3.59-3.56 (m, 1H), 3.35 (s, 3H), 3.35-3.30 (m, 1H), 3.13-3.06 (m, 2H), 2.68-2.67 (m, 1H), 1.92-1.91 (m, 1H), 1.73-1.70 (m, 1H), 1.53-1.49 (m, 2H).  
      MS (ESI+) 506 (M + +1, 100%).  
     Example 41  
       1 H NMR (400 MHz, CD 3 OD) δ ppm 8.25-8.11 (m, 3H), 7.95-7.88 (m, 3H), 7.50-7.49 (m, 1H), 7.36-7.29 (m, 2H), 7.16 (s, 1H), 7.04 (d, J=7.0 Hz, 1H), 5.74 (s, 2H), 3.86-3.83 (m, 1H), 3.58-3.49 (m, 1H), 3.42-3.30 (m, 2H), 3.19-3.10 (m, 1H), 2.13-2.10 (m, 1H), 1.88-1.85 (m, 1H), 1.72-1.67 (m, 2H), 1.22 (d, J=6.8 Hz, 6H).  
      MS (ESI+) 442 (M + +1, 100%).  
     Example 42  
      MS (ESI+) 439 (M + +1, 100%).  
     Example 43  
      MS (ESI+) 400 (M + +1, 64%).  
     Example 44  
     Methyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5,7-dimethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (260 mg) was synthesized from the compound of Reference Example 40 by the same process as in Example 12.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.49-7.47 (m, 1H), 7.30-7.21 (m, 2H), 6.88-6.86 (m, 1H), 5.71 (s, 2H), 4.00 (s, 3H), 3.82-3.72 (m, 1H), 3.50-3.38 (m, 1H), 3.45 (s, 3H), 3.35-3.21 (m, 2H), 3.08-2.98 (m, 1H), 2.32 (s, 3H), 2.16-2.05 (m, 1H), 1.86-1.75 (m, 1H), 1.71-1.59 (m, 2H).  
      MS (ESI+) 444 (M + +1, 100%).  
     Example 45  
     2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5,7-dimethyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      The title compound was synthesized from the compound of Reference Example 43 by the same process as in Example 12.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.51-7.41 (m, 1H), 7.38-7.25 (m, 2H), 7.08-6.98 (m, 1H), 5.80-5.69 (m, 2H), 3.95-3.83 (m, 1H), 3.57 (s, 3H), 3.54-3.30 (m, 3H), 3.20-3.09 (m, 1H), 2.36 (s, 3H), 2.18-2.05 (m, 1H), 1.91-1.77 (m, 1H), 1.75-1.58 (m, 2H).  
      MS (ESI+) 386 (M + +1, 100%).  
     Example 46  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-3,5-dihydro-4H-imidazo[4,5-c]qquinolin-4-one  
     
       
         
         
             
             
         
       
     
      The title compound (33 mg) was synthesized by the same process as in Example 4.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.23-8.18 (m, 1H), 7.47-7.42 (m, 1H), 7.40-7.33 (m, 1H), 7.30-7.24 (m, 1H), 7.23-7.18 (m, 1H), 7.14-7.09 (m, 2H), 6.79-6.75 (m, 1H), 5.76 (d, J=17 Hz, 1H), 5.70 (d, J=17 Hz, 1H), 3.42-3.34 (m, 1H), 3.29-3.20 (m, 1H), 3.04-2.90 (m, 2H), 2.85-2.73 (m, 1H), 1.97-1.84 (m, 1H), 1.81-1.69 (m, 1H), 1.35-1.20 (m, 2H).  
      MS (ESI+) 408 (M + +1, 100%).  
     Example 47  
     Methyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      The title compound (5.3 mg) was synthesized by the same process as in Example 12.  
       1 H NMR (400 MHz, CD 3 OD) δ 8.90 (d, J=1.7 Hz, 1H), 8.12 (dd, J=1.7, 8.7 Hz, 1H), 7.70-7.61 (m, 1H), 7.57-7.47 (m, 1H), 7.34-7.17 (m, 2H), 6.84 (d, J=6.7 Hz, 1H), 5.75 (s, 2H), 3.96 (s, 3H), 3.89-3.85 (d, J=11.8 Hz, 1H), 3.77-3.54 (m, 2H), 3.48-3.32 (m, 1H), 3.13-3.08 (m, 1H), 2.14 (m, 1H), 1.85 (m, 1H), 1.71-1.54 (m, 2H).  
      MS (ESI+) 466 (M + +1, 100%).  
     Example 48  
     2-{(3R)-3-Aminopiperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      The title compound (2.6 mg) was synthesized by the same process as in Example 12.  
       1 H NMR (300 MHz, CD 3 OD) δ 8.89 (d, J=1.8 HZ, 1H), 8.12 (dd, J=1.8, 8.8 Hz, 1H), 7.50-7.46 (m, 2H), 7.33-7.22 (m, 2H), 6.87 (dd, J=1.3, 7.5 Hz, 1H), 5.75 (brs, 1H), 3.83-3.05 (m, 8H), 2.13-2.11 (m, 1H), 1.85-1.82 (m, 1H), 1.73-1.33 (m, 2H).  
      MS (ESI+) 452 (M + +1, 100%).  
      The compounds of Examples 49 to 72 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Example 12.  
                                                                                                          Reference example number       Example number   R 16     R 17     for starting material                                   Example 49   H   6-CO 2 Me   Reference Example 76       Example 50   H   8-CO 2 Me   Reference Example 79       Example 51   H   8-CO 2 H   Reference Example 121       Example 52   H   6-CO 2 H   Reference Example 123       Example 53   H   7-CO 2 Me   Reference Example 78       Example 54   H   7-CO 2 H   Reference Example 120       Example 55   H   7,9-CO 2 Me   Reference Example 80       Example 56   H   7,9-CO 2 H   Reference Example 124       Example 57   H   H   Reference Example 151       Example 58   F   7-CO 2 H   Reference Example 86       Example 59   H   6-MeO/7-CO 2 Et   Reference Example 81       Example 60   H   6,8-F/7-CO 2 Et   Reference Example 82       Example 61   F   8-CO 2 Me   Reference Example 83               Example 62   H                         Reference Example 107               Example 63   H   7-[t-BuC(O)OCH 2 OC(O)]   Reference Example 115       Example 64   F   7-[EtOC(O)OCH(Me)OC(O)]   Reference Example 116       Example 65   H   8-CH 2 CO 2 H   Reference Example 125       Example 66   H   8-CH 2 CO 2 Et   Reference Example 87       Example 67   F   7-MeO/8-CO 2 H   Reference Example 126       Example 68   F   6-MeO/8-CO 2 H   Reference Example 127               Example 69   F                         Reference Example 117               Example 70   F   Me 2 N(CH 2 ) 2 O(O)C   Reference Example 118       Example 71   F   7,9-CO 2 H   Reference Example 128       Example 72   F   7,9-CO 2 Me   Reference Example 91                  
 
     Example 49  
       1 H NMR (300 MHz, CD 3 OD) δ 8.59 (d, J=7.3 Hz, 1H), 7.85 (d, J=7.3 Hz, 1H), 7.52-7.47 (m, 2H), 7.37-7.27 (m, 2H), 7.13 (d, J=6.8 Hz, 1H), 5.78 (s, 2H), 4.05 (brd, J=10.1 Hz, 1H), 3.97 (s, 3H), 3.77-3.71 (m, 1H), 3.68-3.44 (m, 3H), 3.64 (s, 3H), 2.18 (m, 1H), 1.89-1.74 (m, 3H).  
      MS (ESI+) 480 (M + +1, 100%).  
     Example 50  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.70 (d, J=2.0 Hz, 1H), 8.08 (dd, J=2.0, 8.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.51 (dd, J=1.1, 7.7 Hz, 1H), 7.33-7.20 (m, 2H), 6.70 (d, J=7.7 Hz, 1H), 5.63 (d,J=18.1 Hz, 1H), 5.57 (d, J=18.1 Hz, 1H), 3.91 (s, 3H), 3.64 (s, 3H), 3.50-3.37 (m 2H), 3.26-3.19 (m, 1H), 3.11-3.07 (m, 1H), 2.86-2.82 (m, 1H), 1.95 (m, 1H), 1.75 (m, 1H), 1.60-1.54 (m, 2H).  
      MS (ESI+) 480 (M + +1, 100%).  
     Example 51  
       1 H NMR (300 MHz, CD 3 OD) δ 8.96 (d, J=2.0 HZ, 1H), 8.25 (dd, J=2.0, 9.0 Hz, 1H), 7.73 (d, J=9.0 Hz, 1H), 7.49 (dd, J=1.1, 7.7 Hz, 1H), 7.35-7.23 (m, 2H), 6.98 (d, J=8.2 Hz, 1H), 5.71 (s, 2H), 3.93 (brd, J=11.3 Hz, 1H), 3.74-3.37 (m, 3H), 3.64 (s, 3H), 3.21-3.06 (m, 1H), 2.16 (m, 1H), 1.87-1.72 (m, 3H).  
      MS (ESI+) 466 (M + +1, 100%).  
     Example 52  
       1 H NMR (300 MHz, CD 3 OD) δ 8.53 (m, 1H), 7.91-7.88 (m, 1H), 7.51-7.46 (m, 2H), 7.36-7.07 (m, 3H), 5.78 (brs, 2H), 3.75-3.52 (m, 5H), 3.62 (s, 3H), 2.16 (m, 1H), 1.87-1.72 (m, 3H).  
      MS (ESI+) 466 (M + +1, 100%).  
     Example 53  
       1 H NMR (300 MHz, CD 3 OD) δ 8.36 (d, J=8.0 Hz, 1H), 8.25 (brs, 1H), 8.01 (d, J=8.0 Hz, 1H), 7.48 (d, J=6.1 Hz, 1H), 7.33-7.14 (m, 2H), 6.83 (d, J=7.0 Hz, 1H), 5.77 (s, 2H), 3.98 (s, 3H), 3.85-3.72 (m, 1H), 3.75 (s, 3H), 3.67-3.65 (m, 1H), 3.59-3.44 (m, 1H), 3.38-3.25 (m, 1H), 3.08-3.06 (m, 1H), 2.16-2.13 (m, 1H), 1.83-1.59 (m, 3H).  
      MS (ESI+) 480 (M + +1, 100%).  
     Example 54  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.21 (d, J=8.1 Hz, 1H), 8.08 (d, J=1.1 Hz, 1H), 7.90 (dd, J=1.1, 8.1 Hz, 1H), 7.51 (dd, J=1.3, 7.9 Hz, 1H), 7.33-7.19 (m, 2H), 6.68 (d, J=7.5 Hz, 1H), 5.65 (bs, 2H), 3.67 (s, 3H), 3.51-3.43 (m, 1H), 3.35 (m, 1H), 3.25-3.18 (m, 1H), 3.07 (m, 1H), 2.87-2.81 (m, 1H), 2.01-1.94 (m, 1H), 1.76(m, 1H), 1.59-1.52 (m, 2H)  
      MS (ESI+) 466 (M + +1, 100%).  
     Example 55  
       1 H NMR (300 MHz, CD 3 OD) δ 8.22 (s, 1H), 7.87 (s, 1H), 7.47 (d, J=7.9 Hz, 1H), 7.30-7.17 (m, 2H), 6.70 (d, J=7.7 Hz, 1H), 5.75 (brs, 2H), 4.05 (s, 3H), 3.98 (s, 3H), 3.72 (s, 3H), 3.67-3.65 (m, 1H), 3.59-3.57 (m, 1H), 3.47 (m, 1H), 3.11 (m, 1H), 2.94 (m, 1H), 2.11 (m, 1H), 1.82-1.66 (m, 3H).  
      MS (ESI+) 538 (M + +1, 100%).  
     Example 56  
       1 H NMR (300 MHz, CD 3 OD) δ 8.50 (s, 1H), 8.42 (s, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.36-7.24 (m, 2H), 7.00 (d, J=7.7 Hz, 1H), 5.82 (brs, 2H), 3.88-3.18 (m, 5H), 3.81 (s, 3H), 2.14 (m, 1H), 1.84-1.74 (m, 3H).  
      MS (ESI+) 509 (M + +1, 100%).  
     Example 57  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.14 (d, J=7.3 Hz, 1H), 7.61-7.57 (m, 2H), 7.51 (dd, J=1.2, 7.9 Hz, 1H), 7.38-7.13 (m, 3H), 6.64 (d, J=6.2 Hz, 1H), 5.63 (brs, 2H), 3.69-3.62 (m, 4H), 3.33 (m, 1H), 3.24-3.17 (m, 1H), 3.05 (m, 1H), 2.87 (m, 1H), 1.91 (m, 1H), 1.74 (m, 1H), 1.53 (m, 2H).  
      MS (ESI+) 422 (M + +1, 100%).  
     Example 58  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.23 (d. J=8.1 Hz, 1H), 8.10 (bs, 3H), 7.91, (d, J=8.1 Hz, 1H), 7.60 (m, 1H), 7.22 (m, 1H), 6.63 (m, 1H), 5.60 (s, 2H), 3.57 (s, 3H), 3.50 (m, 1H), 3.49 (m, 1H), 3.24 (m, 1H), 3.08 (m, 1H), 2.92 (m, 1H), 2.33 (m, 1H), 1.89 (m, 1H), 1.60-1.55 (m, 2H)  
      MS (ESI+) 484 (M + +1, 100%).  
     Example 59  
       1 H NMR (400 MHz, CD 3 OD) δ 8.14 (d, J=8.2 Hz, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.51 (dd, J=7.9 and 1.3 Hz, 1H), 7.33 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.27 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.95 (d, J=7.9 Hz, 1H), 5.77 (s, 2H), 4.43 (q, J=7.1 Hz, 2H), 3.90 (s, 3H), 3.85 (brs, 1H), 3.80 (s, 3H), 3.54-3.52 (m, 2H), 3.42-3.39 (m, 1H), 3.14-3.08 (m, 1H), 2.15-2.13 (m, 1H), 1.88-1.84 (m, 1H), 1.74-1.67 (m, 2H), 1.43 (t, J=7.1 Hz, 3H).  
      MS (ESI + ) 524 (M + +1, 54%), 400 (77%), 125 (100%).  
     Example 60  
       1 H NMR (400 MHz, CD 3 OD) δ 7.88 (dd, J=8.8 and 1.6 Hz, 1H), 7.49 (dd, J=7.9 and 1.3 Hz, 1H), 7.30 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.23 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.80 (d, J=7.9 Hz, 1H), 5.74 (s, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.88-3.85 (m, 3H), 3.76-3.73 (m, 1H), 3.51 (brs, 1H), 3.20 (brs, 2H), 3.02 (brs, 1H), 2.12 (brs, 1H), 1.81 (brs, 1H), 1.69-1.65 (m, 2H), 1.41 (t, J=7.1 Hz, 3H).  
      MS (ESI + ) 530 (M + +1, 89%), 406 (69%), 125 (100%).  
     Example 61  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.79 (s, 1H), 8.12-8.09 (m, 3H), 7.74 (m, 1H), 7.60 (m, 1H), 7.23 (m, 1H), 6.65 (m, 1H), 5.58 (s, 2H), 3.92 (s, 3H), 3.69 (m, 1H), 3.66 (s, 3H), 3.42 (m, 1H), 3.22 (m, 1H), 3.11 (m, 1H), 2.91 (m, 1H), 2.45 (m, 1H), 1.80 (m, 1H), 1.59-1.55 (m, 2H)  
      MS (ESI+) 498 (M + +1, 100%).  
     Example 62  
       1 H NMR (300 MHz, DMSO) δ 8.24 (d, J=8.3 Hz, 1H), 8.19 (brs, 1H), 8.01 (dd, J=1.5, 8.4 Hz, 1H), 7.52 (dd, J=1.5, 8.1 Hz, 1H), 7.33-7.20 (m, 2H), 6.69 (d, J=6.6 Hz, 1H), 5.64 (brs, 2H), 4.73 (brs, 2H), 3.93-3.19 (m, 13H), 3.71 (s, 3H), 3.10-3.05 (m, 1H), 2.88-2.81 (m, 1H), 2.01-1.90 (m, 1H), 1.77 (m 1H), 1.55 (m, 2H).  
      MS (ESI+) 579 (M + +1, 100%).  
     Example 63  
       1 H NMR (400 MHz, CD 3 OD) δ 8.39 (m, 1H), 8.30 (m, 1H), 8.03 (m, 1H), 7.49 (m, 1H), 7.31 (m, 1H), 7.23 (m, 1H), 6.77 (m, 1H), 6.07 (s, 2H), 5.78 (s, 2H), 3.86 (s, 3H), 3.81 (m, 1H), 3.68 (m, 1H), 3.50 (m, 1H), 3.15 (m, 1H), 2.14 (m, 1H), 1.83 (m, 1H), 1.72-1.64 (m, 2H), 1.33 (m, 1H), 1.25 (s, 9H)  
      MS (ESI+) 580 (M + +1, 100%).  
     Example 64  
       1 H NMR (400 MHz, CD 3 OD) δ 8.45 (m, 1H), 8.24 (s, 1H), 8.02 (m, 1H), 7.57 (m, 1H), 7.13 (m, 1H), 7.04 (m, 1H), 6.81 (m, 1H), 5.72 (s, 2H), 4.23 (1, J=7.08 Hz, 2H), 3.93 (m, 1H), 3.78 (s, 3H), 3.63 (m, 1H), 3.52 (m, 1H), 3.35 (m, 1H). 3.18 (m, 1H), 2.18 (m, 1H), 1.95 (m, 1H), 1.75-1.71 (m, 2H), 1.69 (d, J=5.4 Hz, 3H), 1.33 (m, 3H).  
      MS (ESI+) 600 (M + +1, 100%).  
     Example 65  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.32 (bs, 3H), 8.05 (d, J=1.7 Hz, 1H), 7.55-7.43 (m, 3H), 7.31-7.18 (m, 2H), 6.63 (d, J=7.0 Hz, 1H), 5.63 (s, 2H), 3.73 (s, 2H), 3.70-3.67 (m, 1H), 3.60 (s, 3H), 3.40-3.17 (m, 2H), 3.08-3.05 (m, 1H), 2.85-2.81 (m, 1H), 1.96-1.92 (m, 1H), 1.76-1.73 (m, 1H), 1.56-1.51 (m, 2H).  
      MS (ESI+) 480 (M + +1, 100%).  
     Example 66  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.38 (bs, 3H), 8.08 (d, J=1.9 Hz, 1H), 7.56-7.44 (m, 3H), 7.32-7.14 (m, 2H), 6.66 (d, J=6.8 Hz, 1H), 5.63 (s, 2H), 4.09 (dd, J=7.2, 14.1 Hz, 2H), 3.83 (s, 2H), 3.67-3.65 (m, 1H), 3.66 (s, 3H), 3.29-3.22 (m, 2H), 3.07-3.05 (m, 1H), 2.84-2.81 (m, 1H), 1.95-1.93 (m, 1H), 1.76-1.74 (m, 1H), 1.57-1.53 (m, 2H), 1.19 (d, J=7.0 Hz, 3H).  
      MS (ESI+) 508 (M + +1, 100%).  
     Example 67  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.50 (s, 1H), 8.28 (brs, 3H), 7.58 (dd, J=5.1 and 8.8 Hz, 1H), 7.20 (td, J=3.0 and 8.5 Hz, 1H), 7.05 (s, 1H), 6.62 (dd, J=2.9 and 9.3 Hz, 1H), 5.53 (dd, J=17.9 and 18.1 Hz, 2H), 3.96 (s, 3H), 3.75-3.65 (m, 1H), 3.64 (s, 3H), 3.50-3.40 (m, 1H), 3.30-3.18 (m, 1H), 3.15-3.05 (m, 1H), 2.95-2.85 (m, 1H), 2.00-1.90 (m, 1H), 1.85-1.70 (m, 1H), 1.65-1.45 (m, 2H).  
      MS (ESI+) 514 (M + +1, 100%).  
     Example 68  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.36 (d, J=1.7 Hz, 1H), 8.29 (brs, 3H), 7.58 (d, J=1.7 Hz, 1H), 7.57 (dd, J=5.1 and 8.7 Hz, 1H), 7.20 (td, J=2.9 and 8.5 Hz, 1H), 6.65 (dd, J=2.9 and 9.3 Hz, 1H), 5.55 (dd, J=17.9 and 18.1 Hz, 2H), 3.93 (s, 3H), 3.79 (s, 3H), 3.72-3.62 (m, 1H), 3.45-3.35 (m, 1H), 3.30-3.18 (m, 1H), 3.15-3.05 (m, 1H), 2.95-2.85 (m, 1H), 2.00-1.90 (m, 1H), 1.82-1.70 (m, 1H), 1.68-1.42 (m, 2H).  
      MS (ESI+) 514 (M + +1, 100%).  
     Example 69  
       1 H NMR (400 MHz, CD 3 OD) δ 8.32 (m, 1H), 8.26 (s, 1H), 7.96 (m, 1H), 7.42 (m, 1H), 6.99 (m, 1H), 6.53 (m, 1H). 5.61 (s, 2H), 4.38 (m, 1H), 4.31 (m, 1H), 3.95 (m, 1H), 3.69 (s. 3H), 3.59-3.56 (m, 3H), 3.48-3.40 (m, 2H), 3.26-3.40 (m, 2H), 3.26-3.21 (m, 2H), 3.05-2.98 (m, 1H), 2.03 (m, 1H), 1.75 (m, 1H), 1.68-1.55 (m, 2H)  
      MS (ESI+) 558 (M + +1, 100%).  
     Example 70  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.27 (m, 1H), 8.19 (bs, 3H), 8.04 (m, 1H), 7.61 (m, 1H), 7.23 (m, 1H), 6.65 (m, 1H), 5.60 (s, 2H), 4.68-4.66 (m, 2H), 3.72 (s, 3H), 3.60-3.45 (m, 5H), 3.26 (m, 1H), 3.13 (m, 1H), 2.71 (s, 6H), 2.08 (m, 1H), 1.89 (m, 1H), 1.63-1.55 (m, 2H)  
      MS (ESI+) 555 (M + +1, 100%).  
     Example 71  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.13 (s, 1H), 7.83 (s, 1H), 7.60 (dd, J=5.1, 8.0 Hz, 1H), 7.24-7.12 (m, 1H), 6.65 (dd, J=2.9, 9.3 Hz, 1H), 5.59 (brs, 2H), 3.70 (s, 3H), 3.65-3.55 (m, 1H), 3.49-3.43 (m, 1H), 3.28-3.21 (m, 1H), 3.09-3.05 (m, 1H), 2.95-2.89 (m, 1H), 1.94 (m, 1H), 1.72-1.62 (m, 2H), 1.51-1.49 (m, 1H).  
      MS (ESI+) 528 (M + +1, 100%).  
     Example 72  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.14 (d, J=1.3 Hz, 1H), 7.81 (d, J=1.3 Hz, 1H), 7.58 (dd, J=5.0, 9.3 Hz, 1H), 7.23-7.17 (m, 1H), 6.68 (dd, J=2.9, 9.3 Hz, 1H), 5.62 (d, J=17.4 HZ, 1H), 5.54 (d, J=17.4 Hz, 1H), 3.96 (3, 3H), 3.92 (s, 3H), 3.70 (s, 3H), 3.67-3.63 (m, 1H), 3.55-3.45 (m, 1H), 3.24-3.17 (m, 1H), 3.03-2.99 (m, 1H), 2.83-2.77 (m, 1H), 1.92-1.78 (m, 2H), 1.60-1.54 (m, 2H).  
      MS (ESI+) 556 (M + +1, 100%).  
      The compounds of Examples 73 to 85 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Example 12.  
                                                                                                  Reference example       Example       number for starting       number   R 17     material               Example 73   8-OCHF 2     Reference Example 84       Example 74   7-C(O)NH 2     Reference Example 100       Example 75   7-CN   Reference Example 99               Example 76                         Reference Example 102               Example 77   8-C(O)NMe 2     Reference Example 103       Example 78   7-CH 2 OMe   Reference Example 104       Example 79   7-CO 2 Et   Reference Example 106       Example 80   7-CO 2 (i-Pr)   Reference Example 108       Example 81   7-CO 2 (i-Bu)   Reference Example 109               Example 82                         Reference Example 110               Example 83   7-CO 2 CH(Me)CH(Me) 2     Reference Example 111               Example 84                         Reference Example 112               Example 85   7-CO 2 (CH 2 ) 3 OEt   Reference Example 113                  
 
     Example 73  
       1 H NMR (300 MHz, CD 3 OD) δ 7.87 (d, J=2.9 Hz, 1H), 7.66-7.59 (m, 1H), 7.50 (dd, J=1.5, 8.0 Hz, 1H), 7.39 (dd, J=2.9, 9.2 Hz, 1H), 7.35-7.10 (m, 3H), 6.67 (dd, J=1.4, 7.7 Hz, 1H), 5.64 (brs, 2H), 3.69-3.58 (m, 1H), 3.61 (s, 3H), 3.38-3.20 (m, 2H), 3.10-3.06 (m, 1H), 2.88-2.81 (m, 1H), 1.95-1.89 (m, 1H), 1.75 (m, 1H), 1.61-1.51 (m, 2H).  
      MS (ESI+) 488 (M + +1, 100%).  
     Example 74  
       1 H NMR (400 MHz, CD 3 OD) δ 8.46 (d, J=7.8 Hz, 1H), 8.16 (brs, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.39-7.28 (m, 1H), 7.22-7.08 (m, 2H), 5.75 (brs, 2H), 4.01-3.93 (m, 2H), 3.83-2.97 (m, 6H), 2.17 (m, 1H), 1.88 (m, 1H), 1.74 (m, 2H).  
      MS (ESI+) 465 (M + +1, 100%).  
     Example 75  
       1 H NMR (300 MHz, CD 3 OD) δ 8.52-8.49 (m, 1H), 8.07 (brs, 1H), 7.72 (brd, J=8.3 Hz, 1H), 7.49 (brd, J=7.9 Hz, 1H), 7.35-7.15 (m, 2H), 6.99-6.97 (m, 1H), 5.78 (brs, 2H), 3.95-3.91 (m, 1H), 3.66 (s, 3H), 3.59-3.53 (m, 2H), 3.47-3.34 (m, 1H), 3.16 (m, 1H), 2.15 (m, 1H), 1.85-1.70 (m, 3H).  
      MS (ESI+) 447 (M + +1, 100%).  
     Example 76  
       1 H NMR (300 MHz, CD 3 OD) δ 8.67 (m, 1H), 7.78-7.75 (m, 2H), 7.52-7.44 (m, 1H), 7.36-7.27 (m, 2H), 7.06 (m, 1H), 5.68-5.58 (m, 2H), 4.14-4.10 (m, 1H), 3.86-3.24 (m, 12H), 3.65 (s, 3H), 2.15 (brs, 1H), 1.90-1.74 (m, 3H).  
      MS (ESI+) 535 (M + +1, 100%).  
     Example 77  
       1 H NMR (300 MHz, CD 3 OD) δ 8.60-8.53 (m, 1H), 7.80-7.66(m, 2H), 7.41 (d, J=7.9 Hz, 1H), 7.27-7.13 (m, 2H), 7.10-6.98 (m, 1H), 5.63-5.42 (m, 2H), 4.01 (m, 1H), 3.64-3.55 (m, 2H), 3.55 (s, 3H), 3.49-3.46 (m, 1H), 3.31 (m, 1H), 3.09 (s, 3H), 3.05 (s, 3H), 2.05 (m, 1H), 1.84-1.68 (m, 3H).  
      MS (ESI+) 493 (M + +1, 100%).  
     Example 78  
       1 H NMR (300 MHz, CD 3 OD) 8.37(d, J=8.1 Hz, 1H), 7.66 (brs, 1H), 7.50 (dd, J=1.3, 8.1 Hz, 1H), 7.45 (brd, J=8.0 Hz, 1H), 7.36-7.26 (m, 2H), 7.06 (d, J=7.5 Hz, 1H), 5.80 (brs, 2H), 4.65 (brs, 2H), 3.99 (d, J=9.9 Hz, 1H), 3.74 (s, 3H), 3.74-3.71 (m, 3H), 3.47 (s, 3H), 3.24-3.17 (m 1H), 2.16 (m, 1H), 1.88-1.72 (m, 3H).  
      MS (ESI+) 466 (M + +1,000%).  
     Example 79  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.25 (d, J=8.2 Hz, 1H), 8.08 (d, J=1.2 Hz, 1H), 7.92 (dd, J=1.2, 8.2 Hz, 1H), 7.53 (dd, J=1.1, 7.9 Hz, 1H), 7.32-7.22 (m, 2H), 6.71 (d, J=6.7 Hz, 1H), 5.65 (d, J=17.1 Hz, 1H), 5.58 (d, J=17.1 Hz, 1H), 4.39 (dd, J=7.0, 14.1 Hz, 2H), 3.93-3.66 (m, 1H), 3.68 (s, 3H), 3.26 (brs, 1H), 3.25-3.22 (m, 1H), 3.09-3.06 (m, 1H), 2.89-2.82 (m, 1H), 1.96 (m, 1H), 1.79-1.75 (m, 1H), 1.64-1.52 (m, 2H), 1.38 (t, J=7.0 Hz, 3H).  
      MS (ESI+) 494 (M + +1, 100%).  
     Example 80  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.31 (d, J=8.0 Hz, 1H), 8.14 (d, J=1.3 Hz, 1H), 7.97 (dd, J=1.3, 8.0 Hz, 1H), 7.59 (dd, J=1.3, 7.9 Hz, 1H), 7.40-7.28 (m, 2H), 6.77 (d, J=6.2 Hz, 1H), 5.76 (d, J=17.8 Hz, 1H), 5.65 (d, J=17.8 Hz, 1H), 5.31-5.22 (m, 1H), 3.75 (s, 3H), 3.59-3.50 (m, 1H), 3.40-3.12 (m, 2H), 3.12 (m, 1H), 2.94-2.87 (m, 1H), 2.08-1.97 (m, 1H), 1.82 (m, 1H), 1.67-1.61 (m, 2H), 1.43 (d, J=6.2 Hz, 6H).  
      MS (ESI+) 508 (M + +1, 100%).  
     Example 81  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.24 (d, J=8.3 Hz, 1H), 8.08 (d, J=1.1 Hz, 1H), 7.92 (dd, J=1.1, 8.3 Hz, 1H), 7.51 (dd, J=1.3, 8.0 Hz, 1H), 7.33-7.17 (m, 2H), 6.69 (d, J=6.2 Hz, 1H), 5.65 (d, J=17.8 Hz, 1H), 5.59 (d, J=17.8 Hz, 1H), 4.12 (d, J=6.6 Hz, 2H), 3.67 (s, 3H), 3.51-3.43 (m, 1H), 3.37-3.19 (m, 2H), 3.09-3.05 (m, 1H), 2.87-2.81 (m, 1H), 2.11-1.90 (m, 2H), 1.74 (m, 1H), 1.59-1.56 (m, 2H), 1.00 (d, J=15.8 Hz, 6H).  
      MS (ESI+) 522 (M + +1, 100%).  
     Example 82  
       11 H NMR (300 MHz, DMSO-d 6 ) δ 8.25 (d, J=8.0 Hz, 1H), 8.07 (d, J=1.3 Hz, 1H), 7.91 (dd, J=1.3, 8.0 Hz, 1H), 7.51 (dd, J=1.3, 8.1 Hz, 1H), 7.32-7.20 (m, 2H), 6.70 (d, J=7.4 Hz, 1H), 5.65 (d, J=17.4 Hz, 1H), 5.58 (d, J=17.4 Hz, 1H), 4.37-4.18 (m, 3H), 3.83-3.76 (m, 1H), 3.72-3.64 (m, 2H), 3.67 (s, 3H), 3.32-3.19 (m, 2H), 3.05 (m, 1H), 2.83-2.80 (m, 1H), 2.07-1.54 (m, 8H).  
      MS (ESI+) 550 (M + +1, 100%).  
     Example 83  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.24 (d, J=8.3 Hz, 1H), 8.07 (d, J=1.1 Hz, 1H), 7.91 (dd, J=1.1, 8.3 Hz, 1H), 7.51 (dd, J=1.3, 7.9 Hz, 1H), 7.33-7.20 (m, 2H), 6.69 (d, J=6.0 Hz, 1H), 5.69-5.56 (m, 2H), 4.99-4.92 (m, 1H), 3.67 (s, 3H), 3.73-3.63 (m, 1H), 3.51-3.42 (m, 1H), 3.37-3.19 (m, 2H), 2.84-2.81 (m, 1H), 2.01-1.91 (m, 2H), 1.75 (m, 1H), 1.54 (m, 2H), 1.27 (d, J=6.4 Hz, 3H), 0.97 (dd, J=3.5, 6.6 Hz, 6H).  
      MS (ESI+) 536 (M + +1, 100%).  
     Example 84  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.25 (d, J=8.0 Hz, 1H), 8.07 (brs, 1H), 7.92 (dd, J=0.7, 8.0 Hz, 1H), 7.51 (d, J=7.9 Hz, 1H), 7.32-7.20 (m, 2H), 6.70 (d, J=7.7 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 5.57 (d, J=17.0 Hz, 1H), 4.17 (d, J=7.1 Hz, 2H), 3.67 (s, 3H), 3.67 (m, 1H), 3.33-3.19 (m, 2H), 3.08-3.04 (m, 1H), 2.86-2.80 (m, 1H), 1.95 (m, 1H), 1.74(m, 1H), 1.60-1.54 (m, 2H), 1.33-1.22 (m, 1H), 0.62-0.56 (m, 2H), 0.41-0.36 (m, 2H).  
      MS (ESI+) 520 (M + +1, 100%).  
     Example 85  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.19 (d, J=8.1 Hz, 1H), 8.01 (d, J=1.3 Hz, 1H), 7.86 (dd, J=1.3, 8.1 Hz, 1H), 7.46 (dd, J=1.1, 7.9 Hz, 1H), 7.28-7.14 (m, 2H), 6.64 (d, J=6.4 Hz, 1H), 5.59 (d, J=17.2 Hz, 1H), 5.53 (d, J=17.2 Hz, 1H), 4.33 (m, 2H), 3.70-3.59 (m, 1H), 3.61 (s, 3H), 3.47 (t, J=6.2 Hz, 2H), 3.37 (dd, J=7.0, 14.1 Hz, 2H), 3.27-3.14 (m, 2H), 3.03-2.99 (m, 1H), 2.81-2.75 (m, 1H), 1.97-1.84 (m, 3H), 1.70 (m, 1H), 1.55-1.48 (m, 2H), 1.04 (t, J=7.0 Hz, 3H).  
      MS (ESI+) 552 (M + +1, 100%).  
     Example 86  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid methanesulfonate  
     
       
         
         
             
             
         
       
     
      Methanesulfonic acid (770 μL) was added dropwise to a solution of 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid (1.5 g) in 1,4-dioxane (50 mL), and the resulting mixture was stirred at 90° C. for 4 hours. After the reaction, the solid precipitated was filtered and the thus obtained solid was recrystallized from 2-propanol to obtain the title compound (780 mg) as a white solid.  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.72 (s, 1H), 8.09 (m, 1H), 7.92 (bs, 3H), 7.68 (m, 1H), 7.53 (m, 1H), 7.32-7.24 (m, 2H), 6.70 (m, 1H), 5.62 (s, 2H), 3.70 (m, 1H), 3.67 (s, 3H), 3.38 (m, 1H), 3.19-3.16 (m, 2H), 2.90 (m, 1H), 2.33 (s, 3H), 1.95 (m, 1H), 1.75 (m, 1H), 1.53-1.47 (m, 2H)  
      MS (ESI+) 466 (M + +1, 100%).  
     Example 87  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid methanesulfonate  
     
       
         
         
             
             
         
       
     
      The title compound (447 mg) was obtained as a white solid by the same process as in Example 86.  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 8.77 (s, 1H), 8.09 (m, 1H), 7.95 (bs, 3H), 7.70 (m, 1H), 7.61 (m, 1H), 7.23 (m, 1H), 6.64 (m, 1H), 5.57 (s, 2H), 3.70 (m, 1H), 3.66 (s, 3H), 3.46 (m, 1H), 3.24-3.19 (m, 2H), 2.93 (m, 1H), 1.95 (m, 1H), 1.75 (m, 1H), 1.58-1.53 (m, 2H)  
      MS (ESI+) 484 (M + +1, 100%).  
     Example 88  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid methanesulfonate  
     
       
         
         
             
             
         
       
     
      The title compound (1.2 g) was synthesized by the same process as in Example 86.  
       1 H NMR (400 MHz, CD 3 OD) δ 8.15 (d, J=5.9 Hz, 1H), 8.00 (d, J=12 Hz, 1H), 7.53-7.49 (m, 1H), 7.13-7.06 (m, 1H), 6.68-6.63 (m, 1H), 5.74-5.65 (m, 2H), 3.85-3.78 (m, 1H), 3.75 (s, 3H), 3.62-3.52 (m, 1H), 3.40-3.21 (m, 2H), 3.12-3.01 (m, 1H), 2.70 (s, 3H), 2.17-2.10 (m, 1H), 1.90-1.80 (m, 1H), 1.78-1.63 (m, 2H).  
      MS (ESI+) 502 (M + +1, 100%).  
     Example 89  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxamide trifluoroacetate  
     
       
         
         
             
             
         
       
     
      A 4N hydrochloric acid/1,4-dioxane solution (2 ml) was added to tert-butyl {(3R)-1-[8-(aminocarbonyl)-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate (23.9 mg), and the resulting mixture was stirred at 25° C. for 2 hours. The solvent was removed by concentration under reduced pressure and the residue was purified by a preparative high-performance liquid chromatography to obtain the title compound (8.2 mg) as trifluoroacetate.  
       1 H NMR (300 MHz, CD 3 OD) δ 8.73 (d, J=2.2 Hz, 1H), 8.09 (dd, J=2.2, 9.0 Hz, 1H), 7.66 (d, J=9.0 Hz, 1H), 7.45 (dd, J=1.1, 7.9 Hz, 1H), 7.28-7.09 (m, 2H), 6.65 (d, J=6.4 Hz, 1H), 5.43 (d, J=17.2 Hz, 1H), 5.35 (d, J=17.2 Hz, 1H), 3.77-3.72 (m, 1H), 3.70 (s, 3H), 3.64-3.61 (m, 1H), 3.43-3.34 (m, 1H), 3.07-3.04 (m, 1H), 2.97-2.91 (m 1H), 2.09 (m, 1H), 1.85-1.63 (m, 3H).  
      MS (ESI+) 465 (M + +1, 100%).  
     Example 90  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-5,9-dihydro-3H-furo[3,4-g]imidazo[4,5-c]quinoline-4,7-dione hydrochloride  
     
       
         
         
             
             
         
       
     
      To a solution of tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4,7-dioxo-4,5,7,9-tetrahydro-3H-furo[3,4-g]imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate (3.7 mg) in chloroform (1 mL) was added dropwise 4N hydrochloric acid/1,4-dioxane (1 mL), and the resulting mixture was stirred at room temperature for 4 hours. After the reaction, the solvent was removed under reduced pressure and the resulting solid was washed with acetonitrile and collected by filtration to obtain the title compound (3.8 mg) as a white solid.  
      MS (ESI+) 496 (M + +1, 100%).  
     Example 91  
     (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      To a solution of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-[(3R)-3-(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (53 mg) in chloroform (2 mL) was added dropwise 4N hydrochloric acid/1,4-dioxane (2 mL), and the resulting mixture was stirred at room temperature for 4 hours. After the reaction, the solvent was removed under reduced pressure and the resulting solid was washed with acetonitrile and collected by filtration to obtain the title compound (24.4 mg) as a light-yellow solid.  
       1 H NMR (400 MHz, CH 3 OD) δ 8.95 (s, 1H), 8.26 (m, 1H), 7.75 (m, 1H), 7.52 (m, 1H), 7.10 (m, 1H), 6.62 (m, 1H), 5.69 (s, 2H), 5.00 (s, 2H), 3.81 (m, 1H), 3.78 (s, 3H), 3.56 (m, 1H), 3.10 (m, 1H), 2.29 (s, 3H), 2.15 (m, 2H), 1.86 (m, 1H), 1.73-1.71 (m, 3H)  
      MS (ESI+) 596 (M + +1, 100%).  
     Example 92  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]-1,6-naphthylidin-4-one trifluoroacetate  
     
       
         
         
             
             
         
       
     
      The title compound (1.0 mg) was synthesized by the same process as in Example 89.  
       1 H NMR (400 MHz, CD 3 OD) δ 9.30 (s, 1H), 8.46-8.58 (m, 1H), 7.75-7.66 (m, 1H), 7.46-7.35 (m, 1H), 7.04-6.97 (m, 1H), 6.56-6.48 (m, 1H), 5.65-5.53 (m, 2H), 3.68 (s, 3H), 3.61-2.90 (m, 5H), 2.08-1.95 (m, 1H), 1.85-1.51 (m, 3H).  
      MS (ESI+) 441 (M + +1, 100%).  
     Example 93  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-hydroxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      Ethyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (84.1 mg) was dissolved in 36% hydrochloric acid, and the reaction solution was stirred with heating under reflux for 3 hours. The reaction solution was cooled and then filtered. The white solid thus obtained was dried under reduced pressure to obtain 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-hydroxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride (40.1 mg). In addition, the filtrate was concentrated to obtain 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride (28.3 mg) as a white solid.  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride:  
       1 H NMR (400 MHz, CD 3 OD) δ 8.17 (d, J=8.2 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.51 (d, J=7.9 Hz, 1H), 7.37-7.29 (m, 2H), 7.08 (brs, 1H), 5.77 (brs, 2H), 4.02 (brs, 1H), 3.90 (s, 3H), 3.81 (s, 3H), 3.59-3.40 (m, 3H), 3.22 (brs, 1H), 2.18 (brs, 1H), 1.88 (brs, 1H), 1.74 (brs, 2H).  
      MS (ESI + ) 496 (M + +1, 25%), 372 (59%), 125 (100%).  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6-hydroxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
       1 H NMR (400 MHz, CD 3 OD) δ 7.88 (d, J=8.2 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 7.51 (dd, J=7.9 and 1.3 Hz, 1H), 7.33 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.27 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.96 (d, J=7.9, 1H), 5.77 (s, 2H), 4.00 (s, 3H), 3.94 (brs, 1H), 3.56-3.53 (m, 1H), 3.45-3.35 (m, 2H), 3.16-3.11 (m, 1H), 2.16-2.14 (m, 1H), 1.92-1.85 (m, 1H), 1.74-1.68 (m, 2H).  
      MS (ESI + ) 482 (M + +1, 25%), 358 (50%), 340 (32%), 125 (100%).  
     Example 94  
     Methyl 7-[(3R)-3-aminopiperidin-1-yl]-6-(2-chlorobenzyl)-2-(4-methoxybenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      A solution (3 mL) of methyl 7-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6-(2-chlorobenzyl)-2-(4-methoxybenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydro-imidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate (40.0 mg) in 4N hydrochloric acid/1,4-dioxane was allowed to stand for 48 hours. The solvent was removed and the resulting solid was suspended in diethyl ether. The resulting suspension was filtered and the precipitate was dried to obtain the title compound (26.7 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ ppm 7.49 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.44 (d, J=8.6 Hz, 2H), 7.34-7.19 (m, 2H), 6.87 (d, J=8.6 Hz, 2H), 6.75 (d, J=7.9 Hz, 1H), 5.85 (s, 2H), 5.81 (s, 2H), 3.98-3.95 (m, 6H), 3.90 (s, 3H), 3.78-3.75 (m, 3H), 3.54-3.46 (m, 1H), 3.20-2.95 (m, 3H), 2.13-2.10 (m, 1H), 1.83 (brs, 1H), 1.72-1.65 (m, 2H).  
      MS (ESI + ) 590 (M + +1, 100%).  
     Example 95  
     Methyl 7-[(3R)-3-aminopiperidin-1-yl]-6-(2-chlorobenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      A solution (3 mL) of methyl 7-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6-(2-chlorobenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate (94.6 mg) in 4N hydrochloric acid/1,4-dioxane was allowed to stand for 48 hours. The solvent was removed and the resulting solid was suspended in diethyl ether. The resulting suspension was filtered and the precipitate was dried to obtain the title compound (72.4 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.49 (dd, J=7.9 and 1.3 Hz, 1H), 7.31 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.24 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.86 (d, J=7.9 Hz, 1H), 5.74 (s, 2H), 3.98 (s, 3H), 3.87 (s, 3H), 3.85-3.73 (m, 1H), 3.58-3.47 (m, 2H), 3.26-3.23 (m, 1H), 3.08-3.04 (m, 1H), 2.12 (brs, 1H), 1.87-1.83 (m, 1H), 1.74-1.67 (m, 2H).  
      MS (ESI + ) 470 (M + +1, 100%).  
     Example 96  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6,8-difluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      Ethyl 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-6,8-difluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate hydrochloride (14.7 mg) was dissolved in 36% hydrochloric acid, and the reaction solution was stirred with heating under reflux for 2 hours. The reaction solution was cooled and the solvent was removed under reduced pressure to obtain the title compound (9.7 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.90 (dd, J=8.8 and 1.6 Hz, 1H), 7.49 (dd, J=7.9 and 1.3 Hz, 1H), 7.31 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.24 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.84 (d, J=7.9 Hz, 1H), 5.74 (s, 2H), 3.89-3.86 (m, 3H), 3.79 (dd, J=11.8 and 2.5 Hz, 1H), 3.55-3.53 (m, 1H), 3.36-3.30 (m, 1H), 3.26-3.23 (m, 1H), 3.07-3.02 (m, 1H), 2.15-2.10 (m, 1H), 1.82 (s, 1H), 1.70-1.66 (m, 2H).  
      MS (ESI + ) 502 (M + +1, 86%), 378 (68%), 125 (100%).  
     Example 97  
     2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-9-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      A solution (3 mL) of tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-9-carboxylate (7.7 mg) in 4N hydrochloric acid/1,4-dioxane was allowed to stand for 12 hours. The solvent was removed and the resulting solid was suspended in diethyl ether. The resulting suspension was filtered and the precipitate was dried to obtain the title compound (5.2 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.75-7.71 (m, 1H), 7.49-7.42 (m, 2H), 7.28 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.20 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.73 (d, J=7.9 Hz, 1H), 5.77 (d, J=16.5 Hz, 1H), 5.70 (d, J=16.5 Hz, 1H), 3.75 (s, 3H), 3.70-3.57 (m, 4H), 3.21-3.09 (m, 2H), 1.82-1.57 (m, 3H).  
      MS (ESI + ) 484 (M + +1, 1.00%).  
     Example 98  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      A solution (6 mL) of tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (57.2 mg) in 4N hydrochloric acid/1,4-dioxane was allowed to stand for 72 hours. The solvent was removed and the resulting solid was suspended in diethyl ether. The resulting suspension was filtered and the precipitate was dried to obtain the title compound (46.1 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 8.14 (d, J=5.9 Hz, 1H), 8.04 (d, J=10.6 Hz, 1H), 7.50 (dd, J=7.9 and 1.3 Hz, 1H), 7.32 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.24 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.86 (d, J=7.9 Hz, 1H), 5.76 (s, 2H), 3.84 (dd, J=12.2 and 3.4 Hz, 1H), 3.74 (s, 3H), 3.56-3.53 (m, 1H), 3.39-3.25 (m, 1H), 3.09-3.04 (m, 2H), 2.14 (brs, 1H), 1.86-1.81 (m, 1H), 1.73-1.64 (m, 2H).  
      MS (ESI + ) 484 (M + +1, 100%).  
     Example 99  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-9-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      To a solution (6 mL) of tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-9-methoxy-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (122.1 mg) in 4N hydrochloric acid/1,4-dioxane was added 36% hydrochloric acid (3 ml), and the mixture was stirred at 90° C. for 1 hour. After the reaction solution was cooled, the solvent was removed and the residue was dried under reduced pressure to obtain the title compound (68.2 mg) as a white solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.96 (s, 1H), 7.66 (s, 1H), 7.53 (dd, J=7.9 and 1.3 Hz, 1H), 7.36 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.29 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.04 (d, J=7.9 Hz, 1H), 5.91 (d, J=16.5 Hz, 1H), 5.79 (d, J=16.5 Hz, 1H), 4.22 (s, 3H), 3.94-3.91 (m, 1H), 3.79 (s, 3H), 3.76-3.73 (m, 1H), 3.68-3.64 (m, 2H), 3.59-3.57 (m, 1H), 2.17 (brs, 1H), 1.90 (brs, 1H), 1.77-1.69 (m, 2H).  
      MS (ESI + ) 496 (M + +1, 38%), 372 (100%).  
     Example 100  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(5-fluoro-2-methylbenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-6-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      In 4N hydrochloric acid/1,4-dioxane (10 mL) was dissolved tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(5-fluoro-2-methylbenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (62 mg), and the resulting solution was stirred with heating at 80° C. for 10 hours in a sealed tube. The reaction solution was cooled to 25° C. and then concentrated under reduced pressure, and toluene was added thereto, followed by azeotropic distillation, whereby the title compound (37 mg) was obtained as a light-yellow solid.  
       1 H NMR (300 MHz, DMSO-d 6 ) δ ppm 8.40 (brs, 3H), 8.26 (d, J=8.3 Hz, 1H), 8.07 (s, 1H), 7.90 (d, J=8.1 Hz, 1H), 7.29-7.23 (m, 1H), 7.00-6.95 (m, 1H), 6.34-6.30 (m, 1H), 5.58 (d, J=16.8 Hz, 1H), 5.50 (d, J=16.8 Hz, 1H), 3.67 (s, 3H), 3.41-3.27 (m, 2H), 3.07-3.05 (m, 1H), 2.93-2.71 (m, 2H), 2.34 (s, 3H), 1.94-1.51 (m, 4H).  
      MS (ESI+) 464 (M + +1, 100%).  
     Example 101  
     Methyl 2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-d]thieno[3,4-b]pyridine-6-carboxylate hydrochloride  
     
       
         
         
             
             
         
       
     
      A 4N hydrochloric acid/1,4-dioxane solution (3 mL) was added to methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-d]thieno[3,4-b]pyridine-6-carboxylate (112 mg), and the resulting mixture was stirred at 25° C. for 20 hours. Toluene was added to the reaction solution and the solvent was removed under reduced pressure to obtain the title compound (112 mg) as a yellow solid.  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.41 (s, 1H), 7.50 (dd, J=1.3, 7.9 Hz, 1H), 7.32-7.15 (m, 2H), 6.72 (d, J=7.7 Hz, 1H), 5.59 (d, J=17.2 Hz, 1H), 5.53 (d, J=17.2 Hz, 1H), 3.82 (s, 3H), 3.51 (s, 3H), 3.49-3.42 (m, 1H), 3.30-3.16 (m, 2H), 3.06-3.02 (m, 1H), 2.84-2.78 (m, 1H), 1.93 (m, 1H), 1.74 (m, 1H), 1.60-1.54 (m, 2H).  
      MS (ESI+) 486 (M + +1, 100%).  
     Example 102  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-d]thieno[3,4-b]pyridine-6-carboxylic acid hydrochloride  
     
       
         
         
             
             
         
       
     
      The title compound (110 mg) was synthesized by the same process as in Example 101.  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.30 (s, 1H), 7.50 (dd, J=1.3, 7.9 Hz, 1H), 7.32-7.20 (m, 2H), 6.69 (d, J=7.9 Hz, 1H), 5.56 (brs, 2H), 3.73-3.42 (m, 1H), 3.55 (s, 3H), 3.31 (brs, 1H), 3.20-3.13 (brs, 1H), 3.02 (m, 1H), 2.82 (m, 1H), 1.92-1.90 (m, 1H), 1.77 (m, 1H), 1.54-1.51 (m, 2H).  
      MS (ESI+) 472 (M + +1, 100%).  
     Example 103  
     2-[(3R)-3-Aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-5-methyl-5,8-dihydro-3H-furo[3,4-b]imidazo[4,5-d]pyridine-4,6-dione hydrochloride  
     
       
         
         
             
             
         
       
     
      A 4N hydrochloric acid/1,4-dioxane solution (10 mL) was added to tert-butyl {(3R)-1-[3-(2-chloro-5-fluorobenzyl)-5-methyl-4,6-dioxo-4,5,6,8-tetrahydro-3H-furo[3,4-b]imidazo[4,5-d]pyridin-3-yl]carbamate (10 mg), and the resulting mixture was stirred at 25° C. for 1 hour. After the reaction solution was concentrated under reduced pressure, toluene was added thereto, followed by azeotropic distillation. Thus, the 1,4-dioxane was completely removed to obtain the title compound.  
     Reference Example 1  
     tert-Butyl {(3R)-1-[3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Acetic anhydride (5 mL) and phosphoric acid (0.2 mL) were added to the compound of Reference Example 2 (650 mg), and the resulting mixture was stirred with heating at 80° C. for 2 hours. The precipitate formed was collected by filtration, washed with chloroform and then dried in a desiccator to obtain a product (210 mg) as a white solid. This product was dissolved in N,N-dimethylformamide (10 mL), followed by adding thereto 2-chloro-5-fluorobenzyl bromide (150 μL) and potassium carbonate (256 mg), and the resulting mixture was stirred at room temperature for 16 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to isolation and purification by a silica gel column chromatography (developing solvent: ethyl acetate) to obtain a product (72 mg) as a white amorphous substance. This product was dissolved in ethanol (3 ml), followed by adding thereto (R)-tert-3-butylpiperidin-3-ylcarbamate (227 mg), and the resulting mixture was stirred with heating at 100° C. for 28 hours in a sealed tube. The reaction solution was cooled to 25° C. and then concentrated under reduced pressure, and chloroform was added thereto, followed by washing with a 10% aqueous potassium hydrogensulfate solution. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a preparative thin-layer silica gel chromatography (developing solvent: chloroform/methanol=10/1) to obtain the title compound (68 mg) as a white solid.  
      MS (ESI+) 490 (M + +1, 100%).  
     Reference Example 2  
     2-Bromo-5-methyl-1-(2,3,5-tri-O-t-butyldimethyl-silyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridin-4(5H)-one  
     
       
         
         
             
             
         
       
     
      Potassium carbonate (334 mg), 18-crown-6 (43 mg) and methyl iodide (224 μL) were added to a solution of the compound of Reference Example 3 (830 mg) in N,N-dimethylformamide (20 mL), and the resulting mixture was stirred at 25° C. for 6 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=100/1) to obtain the title compound (650 mg) as a light-yellow solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.05 (m, 2H), 6.03-6.00 (m, 1H), 4.40-4.33 (m, 1H), 4.28-4.23 (m, 1H), 4.21-4.15 (m, 1H), 3.95-3.90 (m, 1H), 3.87-3.81 (m, 1H), 3.64 (s, 3H), 0.99 (s, 9H), 0.95 (s, 9H), 0.78 (s, 9H), 0.18 (s, 3H), 0.17 (s, 3H), 0.13 (s, 3H), 0.10 (s, 3H), 0.00 (s, 3H), −0.15 (s, 3H).  
      MS (ESI+) 704 (M + +3, 100%).  
     Reference Example 3  
     2-Bromo-1-(2,3,5-tri-O-t-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridin-4(5H)-one  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 4 (1.78 g) in tetrahydrofuran (15 mL) was cooled to 0° C. and n-butyllithium (a 1.58M hexane solution, 6.1 mL) was added dropwise thereto. After completion of the dropwise addition, the resulting mixture was stirred at 0° C. After 1.5 hours, 1,2-dibromotetrafluoroethane (1.1 mL) was added dropwise to the reaction solution. After completion of the dropwise addition, the resulting mixture was stirred at room temperature for 2 hours. After the reaction, a saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The dried organic layer was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1) to obtain the title compound (940 mg) as a light-yellow solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.23-7.13 (m, 2H), 6.06-6.00 (m, 1H), 4.46-4.39 (m, 1H), 4.22-4.16 (m, 1H), 4.15-4.10 (m, 1H), 3.99-3.92 (m, 1H), 3.90-3.82 (m, 1H), 0.98 (s, 9H), 0.95(s, 9H), 0.78 (s, 9H), 0.18 (s, 3H), 0.17 (s, 3H), 0.13 (s, 3H), 0.11 (s, 3H), 0.00 (s, 3H), −0.15 (s, 3H).  
      MS (ESI+) 690 (M + +3, 100%).  
     Reference Example 4  
     1-(2,3,5-Tri-O-t-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridin-4(5R)-one  
     
       
         
         
             
             
         
       
     
      A solution consisting of the compound of Reference Example 5 (1.81 g), dimethylamine (a 40% aqueous solution, 10 mL) and ethanol (20 mL) was stirred at 80° C. in an autoclave. After 6 hours, the reaction mixture was concentrated under reduced pressure. To the resulting residue were added ethanol (10 mL) and a 50% aqueous acetic acid solution (10 mL), and the resulting mixture was stirred at 25° C. After 16 hours, the reaction solution was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (50 mL), followed by adding thereto t-butyldimethylsilyl chloride (3.3 g) and imidazole (3.8 g), and the resulting mixture was stirred at 25° C. for 72 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The dried organic layer was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1) to obtain the title compound (1.79 g) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.02 (s, 1H), 7.24-7.20 (m, 1H), 6.81 (d, J=7.1 Hz, 1H), 5.75-5.71 (m, 1H), 4.35-4.30 (m, 1H), 4.20-4.17 (m, 1H), 4.13-4.11 (m, 1H), 3.96-3.92 (m, 1H), 3.84-3.81 (m, 1H), 0.97 (s, 9H), 0.94 (s, 9H), 0.76 (s, 9H), 0.17 (s, 3H), 0.15 (s, 3H), 0.12 (s, 3H), 0.11 (s, 3H), 0.00 (s, 3H), −0.12 (s, 3H)  
      MS (ESI+) 610 (M + +1, 100%).  
     Reference Example 5  
     5-(Trimethylsilylethyn-1-yl)-[(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, trimethyl[(tributyltin)ethynyl]silane (2.9 g) and bis(benzonitrile)palladium(II) chloride (243 mg) were added to a solution of the compound of Reference Example 6 (3.14 g) in acetonitrile (25 mL), and the resulting mixture was stirred at 100° C. for 10 hours in an autoclave. After the reaction, the reaction solution was filtered through Celite and washed with ethanol. The filtrate was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/2 to 0/1) to obtain the title compound (2.17 g) as a brown amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (s, 1H), 6.03-6.01 (m, 1H), 5.53-5.50 (m, 1H), 5.41-5.37 (m, 1H), 4.45-4.42 (m, 1H), 4.40-4.37 (m, 2H), 2.17 (s, 3H), 2.12 (s, 3H), 2.11 (s, 3H), 0.30 (s, 9H).  
      MS (ESI+) 466 (M + +1, 100%).  
     Reference Example 6  
     5-Iodo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-imidazole-4-carboxamide  
     
       
         
         
             
             
         
       
     
      A solution consisting of isopentyl nitrite (3.5 mL) and diiodomethane (25 mL) was heated at 100° C., followed by adding dropwise thereto a solution of 5-amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide (2.0 g) in dichloromethane (10 mL), and the resulting mixture was stirred at 100° C. for 1.5 hours. After the reaction mixture was allowed to cool, the diiodomethane was removed by a silica gel column chromatography (developing solvent: chloroform/methanol=100/0 to 100/5), whereby the title compound (1.75 g) was purified and isolated as a light-yellow solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (s, 1H), 6.02-5.98 (m, 1H), 5.53-5.50 (m, 1H), 5.41-5.33 (m, 1H), 4.46-4.34 (m, 3H), 2.17 (s, 3H), 2.14 (s, 3H), 2.11 (s, 3H).  
      MS (ESI+) 496 (M + +1, 67%).  
     Reference Example 7  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      (R)-tert-3-Butylpiperidin-3-yl carbamate (116 mg) was added to a solution of 2-bromo-3-(2-chlorobenzyl)-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (51 mg) in ethanol (3 mL), and the resulting mixture was stirred with heating at 100° C. for 28 hours in a sealed tube. The reaction solution was cooled to 25° C. and then concentrated under reduced pressure, and chloroform was added thereto, followed by washing with a 10% aqueous potassium hydrogensulfate solution. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a preparative thin-layer silica gel chromatography (developing solvent: chloroform/methanol=10/1) to obtain the title compound (49 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.38 (m, 1H), 7.19-7.12 (m, 2H), 7.09 (d,J=7.2 Hz, 1H), 6.69-6.67 (m, 1H), 6.58 (d, J=7.2 Hz, 1H), 5.78 (d, J=17.0 Hz, 1H), 5.62 (d, J=17.0 Hz, 1H), 4.94-4.92 (m, 1H), 3.78-3.73 (m, 1H), 3.57 (s, 3H), 3.40-3.37 (m, 1H), 3.03-2.98 (m, 3H), 1.76-1.46 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 472 (M + +1, 100%).  
     Reference Example 8  
     2-Bromo-3-(2-chlorobenzyl)-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      The compound of Reference Example 9 and the compound of Reference Example 10 were mixed and the mixture (171 mg) was dissolved in N,N-dimethylformamide (5 mL). Potassium carbonate (103 mg), 18-crown-6 (15 mg) and methyl iodide (92 μL) were added thereto and the resulting mixture was stirred at room temperature for 2 hours. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in ethanol (18 mL), followed by adding thereto 4N hydrochloric acid (24 mL), and the resulting mixture was stirred at 80° C. for 1.5 hours. After the mixture was allowed to cool, the precipitate formed was collected by filtration, washed with chloroform and then dried under reduced pressure to obtain a crude product (90 mg), 2-bromo-5-methyl-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one as a brown solid. The spectrum of this compound is as follows:  
       1 H NMR (400 MHz, DMSO-d 6 ) δ 7.51 (d, J=7.2 Hz, 1H), 6.56 (d, J=7.2 Hz, 1H), 3.55 (s, 3H).  
      MS (ESI+) 228 (M + +1, 100%).  
      Subsequently, potassium carbonate (152 mg) and 2-chlorobenzyl bromide (88 μL) were added to a solution of the above-mentioned product in N,N-dimethylformamide (5 mL), and the resulting mixture was stirred at 25° C. for 14 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate˜chloroform/methanol=10/1) to obtain the title compound (51 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.41 (m, 1H), 7.24-7.13 (m, 2H), 7.13 (d,J=7.2 Hz, 1H), 6.65 (d, J=7.2 Hz, 1H), 6.47-6.45 (m, 1H), 5.92 (s, 2H), 3.59 (s, 3H).  
      MS (ESI+) 352 (M + +1, 85%).  
     Reference Example 9  
     2-Bromo-3-{[2-(trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, a solution of 3-{[2-(trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (119 mg) in tetrahydrofuran (5 mL) was cooled to 0° C., followed by adding dropwise thereto n-butyllithium (0.8 mL, a 1.58M hexane solution), and the resulting mixture was stirred at 0° C. for 1.5 hours. Then, 1,1,2,2-dibromotetrafluoroethane (0.16 mL) was added thereto and the resulting mixture was stirred at 25° C. for 5 hours. A saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1) to obtain the title compound (76 mg) as a light-yellow solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 11.05 (bs, 1H), 7.13 (m, 1H), 6.70 (d, J=7.0 Hz, 1H), 5.93 (s, 2H), 3.72 (t, J=8.2 Hz, 2H), 0.93 (t, J=8.2 Hz, 2H), −0.04 (s, 9H).  
      MS (ESI+) 344 (M + +1, 100%).  
     Reference Example 10  
     2-Bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      Using the compound of Reference Example 11 as a starting material, the title compound (95 mg) was obtained as a light-yellow solid by the same process as in Reference Example 9.  
       1 H NMR (400 MHz, CDCl 3 ) δ 12.63 (bs, 1H), 7.33 (m, 1H), 6.54 (d, J=7.0 Hz, 1H), 5.48 (s, 2H), 3.57 (t, J=8.2 Hz, 2H), 0.91 (t, J=8.2 Hz, 2H), −0.04 (s, 9H).  
      MS (ESI+) 344 (M + +1, 100%).  
     Reference Example 11  
     3-{[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     1-{[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
     
       
         
         
             
             
         
       
     
      Diethoxymethyl acetate (15 mL) was added to 2-chloropyridine-3,4-diamine (480 mg) and the resulting mixture was stirred at room temperature for 12 hours. To the mixture was added 1N hydrochloric acid and the precipitate formed was filtered, washed with diethyl ether and then dried to obtain a crude product (400 mg), 4-chloro-1H-imidazo[4,5-c]pyridine as a brown solid. The spectrum of this compound is as follows:  
       1 H NMR (400 MHz, CD 3 OD) δ 9.45 (s, 1H), 8.51 (d, J=5.9 Hz, 1H), 7.94 (d, J=5.9 Hz, 1H).  
      MS (ESI+) 154 (M + +1, 100%).  
      A hydrochloric acid/methanol solution (25 mL, methanol component 80-90%) was added to this solid (220 mg) and the resulting mixture was heated under reflux for 30 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure, and the resulting residue was washed with diethyl ether and dried to obtain a crude product (150 mg), 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one as a brown solid. The spectrum of this compound is as follows:  
       1 H NMR (400 MHz, CD 3 OD) δ 9.40 (s, 1H), 7.58 (d, J=7.2 Hz, 1H), 6.87 (d, J=7.2 Hz, 1H).  
      MS (ESI+) 136 (M++1, 100%).  
      Under a nitrogen atmosphere, sodium hydride (134 mg, a 60% oil dispersion) was added to N,N-dimethylformamide (15 mL) and the resulting suspension was cooled to −15° C. To the suspension was added 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (360 mg) and the resulting mixture was stirred at room temperature for 30 minutes. Then, chloro-2-(trimethylsilyl)ethoxymethane (0.550 mL) was added dropwise thereto, followed by stirring at room temperature for 20 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1 to 10/1) to obtain 3-{[2-(trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (119 mg) and 1-{[2-(trimethyl-silyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (113 mg) each as a white solid.  
     3-{[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
       1 H NMR (400 MHz, CDCl 3 ) δ 11.49 (bs, 1H), 8.03 (s, 1H), 7.16 (m, 1H), 6.77 (d, J=7.0 Hz, 1H), 5.91 (s, 2H), 3.66 (t, J=8.2 Hz, 2H), 0.93 (t, J=8.2 Hz, 2H) 0.04 (s, 9H).  
      MS (ESI+) 266 (M + +1, 100%).  
     1-{[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one  
       1 H NMR (400 MHz, CDCl 3 ) δ 10.97 (bs, 1H), 7.84 (s, 1H), 7.21 (m, 1H), 6.56 (d, J=7.1 Hz, 1H), 5.45 (s, 2H), 3.51 (t, J=8.2 Hz, 2H), 0.90 (t, J=8.2 Hz, 2H), −0.03 (s, 9H).  
      MS (ESI+) 266 (M + +1, 100%).  
     Reference Example 12  
     2-Chloropyridine-3,4-diamine  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, potassium t-butoxide (28 g) was added to a solution of zinc(II) chloride (8.6 g) in dimethoxyethane (200 mL) in small portions while cooling the solution in an ice bath. To this solution was added dropwise a solution of 2-chloro-3-nitropyridine (10 g) and O-methylhydroxylamine hydrochloride (7.9 g) in dimethyl sulfoxide (25 ml)/dimethoxyethane (25 ml), and the resulting mixture was stirred at room temperature for 50 hours. A saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The extract solution was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate=5/1 to 2/1). A solution of the thus obtained crude product (2.43 g) in methanol (50 mL) was added dropwise to a solution of titanium(III) chloride (65 g, a 20% aqueous solution) in methanol (50 mL), and the resulting mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water and sodium hydrogencarbonate was added thereto until no more carbon dioxide production was observed. The resulting solution was diluted with water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=30/1 to 10/1) to obtain the title compound (1.4 g) as a brown solid.  
       1 H NMR (400 MHz, CD 3 OD) δ 7.41 (d, J=5.4 Hz, 1H), 6.56 (d, J=5.4 Hz, 1H).  
      MS (ESI+) 144 (M + +1, 100%).  
     Reference Example 13  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      Methyl iodide (1.25 mL) was added to a solution of the compound of Reference Example 17 (2.00 g) and potassium carbonate (1.38 g) in N,N-dimethylformamide (30 mL), and the resulting mixture was stirred at 25° C. for 16 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (1.3 g) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.38 (m, 1H), 7.34 (s, 1H), 7.23-7.12 (m, 2H), 6.70-6.64(m, 1H), 5.79 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 3.93 (s, 3H), 3.84-3.72 (m, 1H), 3.72 (s, 3H), 3.45-3.38 (m, 1H), 3.09-2.95 (m, 3H), 1.84-1.52 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 530 (M + +1, 100%).  
     Reference Example 14  
     3-(Diethylamino)propyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 17 (100 mg), 3-diethylamino-1-propanol (45 μL), 1-hydroxybenzotriazole (40 mg), 1-ethyl-3-(dimethylaminopropyl)carbo-diimide hydrochloride (50 mg) and triethylamine (84 μL) in N,N-dimethylformamide (2 mL) was stirred at 25° C. for 16 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1) to obtain the title compound (27 mg) as a white amorphous substance.  
      MS (ESI+) 615 (M + +1, 100%).  
     Reference Example 15  
     2-Morpholin-4-yl ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 17 (100 mg), N-(2-hydroxyethyl)morpholine (36 μL), 1-hydroxybenzotriazole (40 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (50 mg) and triethylamine (84 μL) in dimethylformamide (2 mL) was stirred at 25° C. for 16 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=20/1) to obtain the title compound (35 mg) as a white amorphous substance.  
      MS (ESI+) 615 (M + +1, 100%).  
     Reference Example 16  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      To a solution of the compound of Reference Example 17 (1.4 g) in methanol (25 mL) were added 1-hydroxybenzotriazole (555 mg) and 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (695 mg), and the resulting mixture was stirred at 25° C. for 14 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (1.01 g) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.61 (s, 1H), 7.45-7.38 (m, 1H), 7.26-7.13 (m, 2H), 6.76-6.69(m, 1H), 5.85 (d, J=17.0 Hz, 1H), 5.68 (d, J=17.0 Hz, 1H), 3.82-3.70 (m, 1H), 3.49 (s, 3H), 3.49-3.40 (m, 1H), 3.10-2.98 (m, 3H), 1.87-1.53 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 516 (M + +1, 31%).  
     Reference Example 17  
     2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid  
     
       
         
         
             
             
         
       
     
      Palladium(II) acetate (974 mg) was added to a solution of the compound of Reference Example 18 (12.7 g), methyl 2-acetamidoacrylate (4.7 g), benzyltriethylammonium chloride (4.9 g) and sodium hydrogencarbonate (3.6 g) in dimethylformamide (65 mL), and the resulting mixture was stirred with heating at 80° C. for 4 hours. The reaction mixture was allowed to cool and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1 to 0/1) to obtain a product (10.3 g) as a brown amorphous substance [MS (ESI+) 604 (M + , 52%)].  
      A solution consisting of this product (10.3 g), ethanol (30 mL) and sodium ethoxide (a 21% ethanol solution, 29 mL) was stirred with heating at 80° C. After 4 hours, the solution was cooled to 25° C. and a 1N aqueous sodium hydroxide solution (15 mL) was added thereto, followed by stirring at 50° C. for 1 hour. The reaction mixture was cooled to 25° C., adjusted to pH 7-8 with a saturated aqueous ammonium chloride solution, and then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to obtain the title compound (6.87 g) as an orange amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.61 (s, 1H), 7.47-7.40 (m, 1H), 7.29-7.11 (m, 2H), 6.75-6.66(m, 1H), 5.85 (d, J=17.0 Hz, 1H), 5.68 (d, J=17.0 Hz, 1H), 3.82-3.70 (m, 1H), 3.50-3.39 (m, 1H), 3.11-2.98 (m, 3H), 1.87-1.53 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 502 (M + +1, 38%).  
     Reference Example 18  
     Ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 19 (20 g), isopentyl nitrite (28 mL) and diiodomethane (33 mL) in toluene (200 mL) was stirred with heating at 80° C. for 3 hours. After the reaction, the reaction mixture was concentrated under reduced pressure and the residue was subjected to isolation and purification by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=5/1 to 1/1) to obtain the title compound (18 g).  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.23-7.13 (m, 2H), 6.62-6.55 (m, 1H), 5.51-5.37 (m, 2H), 4.18 (q, J=7.1 Hz, 2H), 3.80-3.69 (m, 1H), 3.32-3.23 (m, 1H), 2.97-2.84 (m, 3H), 1.80-1.45 (m, 4H), 1.42 (s, 9H), 1.18 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 589 (M + +1, 46%).  
     Reference Example 19  
     Ethyl 4-amino-2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      Sodium hydride (60%, 2.01 g) was added to tetrahydrofuran (223 mL) at room temperature and stirred for 30 minutes. A solution (100 mL) of ethyl N-[(Z)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]-N-(2-chlorobenzyl)glycinate (16.0 g) in tetrahydrofuran was added to the reaction solution at 80° C. and stirred at room temperature for 2 hours. The reaction solution was cooled to 0° C. and water (1.8 mL) was carefully added thereto, followed by adding thereto a saturated aqueous ammonium chloride solution (10 mL). The reaction solution was concentrated under reduced pressure and water and potassium carbonate were added to the residue to obtain an alkaline solution, followed by two runs of extraction with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound as a crude product (16.7 g).  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.39 (dd, J=1.6, 7.7 Hz, 1H), 7.23-7.18 (m, 2H), 6.81-6.76 (m, 1H), 5.31 (s, 2H), 5.23-5.03 (m, 1H), 4.12 (q, J=7.1 Hz, 2H), 3.82-3.77 (m, 1H), 3.38-3.33 (m, 1H), 3.05-3.00 (m, 3H), 1.80-1.75 (m, 2H), 1.62-1.57 (m, 2H), 1.41 (s, 9H), 1.02 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 478 (M + +1, 100%).  
     Reference Example 20  
     Ethyl N-[(Z)-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}(cyanoimino)methyl]-N-(2-chlorobenzyl)glycinate  
     
       
         
         
             
             
         
       
     
      2-Chlorobenzyl bromide (18.3 g) and potassium carbonate (24.6 g) were added to a solution (113 mL) of ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]glycinate (21.0 g) in acetonitrile at room temperature, and the resulting mixture was stirred at 70° C. for 2 hours. The reaction mixture was allowed to cool and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1 to 2/3) to obtain the title compound (16.3 g).  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.45-7.40 (m, 1H), 7.34-7.29 (m 3H), 4.63-4.58 (m, 2H), 4.22 (q, J=7.1 Hz, 2H), 4.03-3.98 (m, 2H), 3.76-3.71 (m, 2H), 3.54-3.25 (m, 4H), 1.95-1.90 (m, 2H), 1.71-1.59 (m, 2H), 1.44 (s, 9H), 1.29 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 478 (M + +1, 82%).  
     Reference Example 21  
     Ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}(cyanoimino)methyl]glycinate  
     
       
         
         
             
             
         
       
     
      (R)-tert-3-Butyl piperidin-3-ylcarbamate (73.0 g) was added to a suspension (1.46 L) of diphenyl cyanoimidocarbonate (86.8 g) in 2-propanol at room temperature, and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was heated to 50° C., followed by adding thereto glycine ethyl ester hydrochloride (254 g) and triethylamine (254 mL), and the reaction mixture was further heated and then stirred at 80° C. for 6 hours. The reaction mixture was allowed to cool to room temperature and the precipitate was collected by filtration and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and water and potassium carbonate were added to the residue to obtain an alkaline solution, followed by two runs of extraction with chloroform. The combined organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to 0/1) to obtain the title compound (133 g) as an amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 5.61 (brs, 1H), 4.66 (brs, 1H), 4.24 (q, J=7.1 Hz, 2H), 4.25-4.20 (m, 1H), 3.78-3.37 (m, 5H), 1.98-1.93 (m, 1H), 1.85-1.80 (m, 1H), 1.71-1.66 (m, 2H), 1.45 (s, 9H), 1.30 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 354 (M + +1, 20%).  
     Reference Example 22  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-5-(2-oxo-2-phenylethyl)-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of Reference Example 29 (53 mg), phenacyl bromide (26 mg) and potassium carbonate (50 mg) in N,N-dimethylformamide (1.5 mL) was stirred at room temperature for 6 hours. After the reaction, water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to 0/1) to obtain the title compound (52 mg) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.05-7.98 (m, 2H), 7.63-7.57 (m, 1H), 7.52-7.43 (m, 2H), 7.40-7.32 (m, 1H), 7.21-7.10 (m, 2H), 7.03 (d, J=7.2 Hz, 1H), 6.75-6.70 (m, 1H), 6.68 (d,J=7.2 Hz, 1H), 5.74 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 5.42 (s, 2H), 3.86-3.71 (m, 1H), 3.41-3.32 (m, 1H), 3.09-2.91 (m, 3H), 1.82-1.53 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 576 (M + +1, 100%).  
     Reference Example 23  
     Ethyl[2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-3,4-dihydro-5H-imidazo[4,5-c]pyridin-5-yl]acetate  
     
       
         
         
             
             
         
       
     
      The title compound (121 mg) was synthesized by the same process as in Reference Example 22.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.22-7.10 (m, 2H), 7.02 (d, J=7.2 Hz, 1H), 6.71-6.68 (m, 1H), 6.63 (d, J=7.2 Hz, 1H), 5.75 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 4.68 (s, 2H), 4.21 (q, J=7.2 Hz, 2H), 3.86-3.71 (m, 1H), 3.41-3.32 (m, 1H), 3.06-2.94 (m, 3H), 1.80-1.49 (m, 4H), 1.43 (s, 9H), 1.25 (t, J=7.2 Hz, 3H).  
      MS (ESI+) 544 (M + +1, 100%).  
     Reference Example 24  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-5-[2-(2-methoxyphenyl)-2-oxoethyl]-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (86 mg) was synthesized by the same process as in Reference Example 22.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.95-7.89 (m, 1H), 7.66-7.57 (m, 1H), 7.40-7.32 (m, 1H), 7.20-7.11 (m, 2H), 7.05-6.95 (m, 3H), 6.74-6.69 (m, 1H), 6.66 (d, J=7.2 Hz, 1H), 5.75 (d,J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 5.34 (s, 2H), 3.96 (s, 3H), 3.85-3.73 (m, 1H), 3.41-3.32 (m, 1H), 3.08-2.95 (m, 3H), 1.83-1.55 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 606 (M + +1, 100%).  
     Reference Example 25  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-5-[2-(3-methoxyphenyl)-2-oxoethyl]-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (71 mg) was synthesized by the same process as in Reference Example 22.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.63-7.53 (m, 1H), 7.53-7.51 (m, 1H), 7.42-7.34 (m, 2H), 7.23-7.10 (m, 3H), 7.02 (d, J=7.2 Hz, 1H), 6.74-6.69 (m, 1H), 6.68 (d, J=7.2 Hz, 1H), 5.74 (d, J=17.0 Hz, 1H), 5.60 (d, J=17.0 Hz, 1H), 5.40 (s, 2H), 3.83 (s, 3H), 3.83-3.72 (m, 1H), 3.43-3.35 (m, 1H), 3.08-2.93 (m, 3H), 1.75-1.49 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 606 (M + +1, 100%).  
     Reference Example 26  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-(1-methyl-2-oxo-2-phenylethyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (78 mg) was synthesized by the same process as in Reference Example 22.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.97-7.92 (m, 2H), 7.56-7.49 (m, 1H), 7.45-7.32 (m, 3H), 7.28-7.18 (m, 1H), 7.17-7.09 (m, 1H), 7.07-7.00 (m, 1H), 6.67-6.58 (m, 2H), 5.85-5.72 (m, 1H), 5.69-5.58 (m, 1H), 4.99-4.88 (m, 1H), 3.82-3.71 (m, 1H), 3.41-3.31 (m, 1H), 3.04-2.93 (m, 3H), 1.79-1.48 (m, 4H), 1.62-1.61 (m, 3H), 1.42 (s, 9H).  
      MS (ESI+) 590 (M + +1, 100%).  
     Reference Example 27  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-5-(2-phenoxyethyl)-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (47 mg) was synthesized by the same process as in Reference Example 22.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.31-7.08 (m, 5H), 6.95-6.88 (m, 1H), 6.86-6.78 (m, 2H), 6.70-6.63 (m, 1H), 6.60-6.57 (m, 1H), 5.75 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 4.37-4.34 (m, 1H), 4.25-4.22 (m, 2H), 3.82-3.71 (m, 2H), 3.41-3.32 (m, 1H), 3.03-2.90 (m, 3H), 1.78-1.49 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 578 (M + +1, 100%).  
     Reference Example 28  
     [2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-3,4-dihydro-5H-imidazo[4,5-c]pyridin-5-yl]acetic acid  
     
       
         
         
             
             
         
       
     
      The compound of Reference Example 23 (73 mg) was dissolved in ethanol (2 mL), followed by adding thereto a 1N aqueous sodium hydroxide solution (0.5 mL), and the resulting mixture was stirred at 80° C. for 1 hour. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure, and a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (32 mg) as a white amorphous substance.  
      MS (ESI+) 516 (M + +1, 100%).  
     Reference Example 29  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution consisting of the compound of Reference Example 30 (1.8 g), dimethylamine (a 40% aqueous solution, 17 mL) and ethanol (25 mL) was stirred at 80° C. for 4 hours in an autoclave. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure, and the resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate) to obtain the title compound (1.3 g) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.38 (m, 1H), 7.22-7.10 (m, 2H), 7.01 (d, J=7.1 Hz, 1H), 6.73-6.68 (m, 1H), 6.61 (d, J=7.1 Hz, 1H), 5.76 (d, J=17.0 Hz, 1H), 5.62 (d, J=17.0 Hz, 1H), 3.83-3.72 (m, 1H), 3.43-3.35 (m, 1H), 3.08-2.94 (m, 3H), 1.82-1.49 (m, 4H), 1.4 (s, 9H).  
      MS (ESI+) 458 (M + +1, 100%).  
     Reference Example 30  
     tert-Butyl((3R)-1-{5-(aminocarbonyl)-1-(2-chlorobenzyl)-4-[(trimethylsilyl)ethynyl]-1H-imidazol-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, bis(benzonitrile)-palladium(II) chloride (38 mg) was added to a solution (3 mL) of the compound of Reference Example 31 (368 mg) and trimethyl[(tributyltin)ethynyl]silane (382 mg) in acetonitrile, and the resulting mixture was stirred at 80° C. for 3 hours. The reaction mixture was cooled to 25° C. and filtered through Celite and the filtrate was subjected to isolation and purification by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1 to 1/1) to obtain the title compound (257 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.34 (m, 1H), 7.23-7.12 (m, 2H), 6.60-6.54 (m, 1H), 5.65(d, J=17.0 Hz, 1H), 5.55 (d, J=17.0 Hz, 1H), 3.81-3.70 (m, 1H), 3.40-3.32 (m, 1H), 2.91-2.78 (m, 3H), 1.79-1.47 (m, 4H), 1.42 (s, 9H), 0.27 (s, 9H).  
      MS (ESI+) 530 (M + +1, 86%).  
     Reference Example 31  
     tert-Butyl {(3R)-1-[5-(aminocarbonyl)-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution consisting of the compound of Reference Example 18 (7.0 g), 1N sodium hydroxide (20 mL) and ethanol (50 mL) was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure and a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (100 mL), followed by adding thereto 1-hydroxybenzotriazole (3.1 g), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (3.8 g), triethylamine (8.8 mL) and ammonium chloride (1.2 g), and the resulting mixture was stirred at 25° C. for 24 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (6.54 g) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.34 (m, 1H), 7.22-7.13 (m, 2H), 6.71-6.65 (m, 1H), 5.58(d, J=17.0 Hz, 1H), 5.51 (d, J=17.0 Hz, 1H), 3.80-3.71 (m, 1H), 3.31-3.23 (m, 1H), 2.92-2.81 (m, 3H), 1.81-1.49 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 560 (M + +1, 32%).  
     Reference Example 32  
     tert-Butyl {(3R)-1-[6-acetyl-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 46 (90 mg) in tetrahydrofuran (2 mL) was cooled to 0° C., followed by adding dropwise thereto methylmagnesium bromide (0.68 mL), and the resulting mixture was stirred at 0° C. After 1 hour, the mixture was heated to 25° C. and stirred for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (53 mg) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.36 (m, 1H), 7.29 (s, 1H), 7.24-7.11 (m, 2H), 6.70-6.62 (m, 1H), 5.80 (d, J=17.0 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 3.84-3.72 (m, 1H), 3.56 (s, 3H), 3.49-3.39 (m, 1H), 3.08-2.92 (m, 3H), 2.61 (s, 3H), 1.83-1.48 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 514 (M + +1, 100%).  
     Reference Example 33  
     tert-Butyl {(3R)-1-[6-benzoyl-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (53 mg) was synthesized by the same process as in Reference Example 32.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.95-7.90 (m, 2H), 7.70-7.63 (m, 1H), 7.55-7.48 (m, 2H), 7.44-7.38 (m, 1H), 7.26-7.15 (m, 2H), 6.82 (s, 1H), 6.75-6.69 (m, 1H), 5.82 (d, J=17.0 Hz, 1H), 5.66 (d, J=17.0 Hz, 1H), 3.82-3.71 (m, 1H), 3.57 (s, 3H), 3.43-3.35 (m, 1H), 3.07-2.94 (m, 3H), 1.81-1.47 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 576 (M + +1, 100%).  
     Reference Example 34  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-6-[(3-methoxyphenyl)acetyl]-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      Cerium trichloride hexahydrate (381 mg) was dehydrated and dried at 140° C. for 3 hours with a vacuum pump. The dried compound was suspended in tetrahydrofuran at 0° C. and 3-methoxybenzylmagnesium bromide (1.0 M, 1.06 mL) was added dropwise thereto. After 30 minutes, a solution of the compound of Reference Example 46 (200 mg) in tetrahydrofuran (2 mL) was added and the resulting mixture was stirred at 0° C. After 1 hour, the mixture was heated to 25° C. and stirred for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (121 mg) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.41-7.38 (m, 1H), 7.28-7.15 (m, 4H), 6.86-6.82 (m, 2H), 6.81 (s, 1H), 6.68-6.65 (m, 1H), 5.79-5.60 (m, 2H), 4.82-4.80 (m, 1H), 4.15 (s, 2H), 3.81-3.80 (m, 1H), 3.79 (s, 3H), 3.49 (s, 3H), 3.44-3.39 (m, 1H), 3.03-2.96 (m, 3H), 1.80-1.76 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 620 (M + +1, 100%).  
     Reference Example 35  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4-oxo-6-(phenylacetyl)-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (54 mg) was synthesized by the same process as in Reference Example 34.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.27 (m, 7H), 7.15-7.14 (m, 2H), 6.67 (d, J=7.2 Hz, 1H), 5.80-5.59 (m, 2H), 4.84-4.82 (m, 1H), 4.19 (s, 2H), 3.79-3.75 (m, 1H), 3.48 (s, 3H), 3.44-3.40 (m, 1H), 3.04-2.96 (m, 3H), 1.80-1.75 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 590 (M + +1, 100%).  
     Reference Example 36  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-(3-methoxybenzoyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (91 mg) was synthesized by the same process as in Reference Example 34.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.49-7.39 (m, 4H), 7.26-7.18 (m, 3H), 6.83 (s, 1H), 6.72 (d, J=7.3 Hz, 1H), 5.84-5.64 (m, 2H), 4.86-4.84 (m, 1H), 3.88 (s, 3H), 3.85-3.82 (m, 1H), 3.56 (s, 3H), 3.42-3.39 (m, 1H), 3.04-2.97 (m, 3H), 1.79-1.74 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 606 (M + +1, 100%).  
     Reference Example 37  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-isobutyryl-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (10 mg) was synthesized by the same process as in Reference Example 32.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.41-7.39 (m, 1H), 7.21-7.16 (m, 2H), 7.08 (s, 1H), 6.69 (d, J=7.2 Hz, 1H), 5.81-5.61 (m, 2H), 4.82 (d, J=8.2 Hz, 1H), 3.81-3.71 (m, 1H), 3.55 (s, 3H), 3.41 (dd, J=3.3 Hz, 8.2 Hz, 1H), 3.38-3.31 (m, 1H), 3.04-2.96 (m, 3H), 1.79-1.52 (m, 4H), 1.42 (s, 9H), 1.24-1.22 (m, 6H).  
      MS (ESI+) 542 (M + +1, 100%).  
     Reference Example 38  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-6-(1,3-oxazol-5-yl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Potassium carbonate (21 mg) and p-toluenesulfonylmethyl isocyanide (30 mg) were added to a solution of the compound of Reference Example 39 (70 mg) in methanol, and the resulting mixture was heated under reflux for 4 hours. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure, and water was added thereto, followed by extraction with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (ethyl acetate) to obtain the title compound (60 mg) as a colorless amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (s, 1H), 7.43-7.36 (m, 1H), 7.25-7.13 (m, 2H), 6.86 (s, 1H), 6.75-6.68 (m, 1H), 5.79 (d, J=17 Hz, 1H), 5.64 (d, 17 Hz, 1H), 3.85-3.74 (m, 1H), 3.54 (s, 3H), 3.45-3.35 (m, 1H), 3.08-2.95 (m, 3H), 1.83-1.52 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 539 (M + +1, 100%).  
     Reference Example 39  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-formyl-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Manganese(IV) oxide (210 mg) was added to a solution of the compound of Reference Example 64 (300 mg) in chloroform, and the resulting mixture was stirred at 50° C. for 6 hours and then at room temperature for 16 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (hexane/ethyl acetate=1/1) to obtain the title compound (262 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 9.55 (s, 1H), 7.45-7.38 (m, 1H), 7.27-7.13 (m, 3H), 6.70-6.63 (m, 1H), 5.82 (d, J=17 Hz, 1H), 5.65 (d, J=17 Hz, 1H), 3.88 (s, 3H), 3.82-3.72 (m, 1H), 3.50-3.41 (m, 1H), 3.12-2.94 (m, 3H), 1.86-1.45 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 500 (M + +1, 100%).  
     Reference Example 40  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5,7-dimethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 41 (1.0 g) and 1,8-diazabicyclo[5,4,0]-7-undecene (532 μL) in toluene (20 mL) was heated under reflux for 10 hours by the use of a Dean-Stark trap to remove water azeotropically. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure, and water was added thereto, followed by extraction with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=1/1) to obtain the title compound (310 mg) as a colorless amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.37 (m, 1H), 7.21-7.10 (m, 2H), 6.68-6.60 (m, 1H), 5.73 (d, J=17 Hz, 1H), 5.60 (d, J=17 Hz), 3.98 (s, 3H), 3.81-3.71 (m, 1H), 3.49 (s, 3H), 3.40-3.32 (m, 1H), 3.28-3.19 (m, 1H), 3.10-2.95 (m, 2H), 2.34 (s, 3H), 1.78-1.60 (m, 3H), 1.52-1.43 (m, 1H), 1.42 (s, 9H).  
      MS (ESI+) 544 (M + +1, 100%).  
     Reference Example 41  
     Methyl N-{[4-acetyl-2-{(3R)-3-[(tert-butoxy-carbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-1H-imidazol-5-yl]carbonyl}-N-methylglycinate  
     
       
         
         
             
             
         
       
     
      A mixed solution consisting of the compound of Reference Example 42 (2.2 g), a 1N aqueous sodium hydroxide solution (10 mL) and ethanol (20 ml) was stirred at 80° C. for 2 hours. After the reaction solution was cooled to 25° C., a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylform-amide (45 mL), followed by adding thereto 1-hydroxybenzotriazole (1.1 g), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (1.3 g), triethylamine (3.2 mL) and sarcosine methyl ester hydrochloride (1.0 g), and the resulting mixture was stirred at 25° C. for 20 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic phase was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=1/1→1/3) to obtain the title compound (1.0 g) as a colorless amorphous substance.  
      MS (ESI+) 562 (M + +1, 60%).  
     Reference Example 42  
     Ethyl 4-acetyl-2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, tributyl(1-ethoxyvinyl)tin (4.0 mL) and dichlorobis(benzonitrile)-palladium(II) (460 mg) were added to a solution of the compound of Reference Example 18 (4.7 g) in acetonitrile (40 mL), and the resulting mixture was stirred at 80° C. for 9 hours. The reaction mixture was cooled to 25° C. and filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1→1/1) to obtain a brown amorphous substance (2.5 g). To this compound were added a 5% aqueous potassium hydrogensulfate solution (50 mL) and tetrahydrofuran (50 mL), and the resulting mixture was stirred at 25° C. for 110 hours. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (2.2 g) as a colorless amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.39-7.37 (m, 1H), 7.25-7.16 (m, 2H), 6.72-6.70 (m, 1H), 5.33 (s, 2H), 4.16 (q, J=7.2 Hz, 2H), 3.80-3.72 (m, 1H), 3.32-3.22 (m, 1H), 3.04-2.87 (m, 3H), 2.59 (s, 3H), 1.80-1.46 (m, 4H), 1.52 (s, 9H), 1.15 (t, J=7.2 Hz, 3H).  
      MS (ESI+) 505 (M + +1, 29%).  
     Reference Example 43  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5,7-dimethyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 44 (28 mg), potassium carbonate (22 mg) and methyl iodide (8 μL) in N,N-dimethylformamide (1 mL) was stirred at room temperature for 12 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic phase was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (ethyl acetate) to obtain the title compound (15 mg) as a light-yellow amorphous substance.  
      MS (ESI+) 486 (M + +1, 100%).  
     Reference Example 44  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-7-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, palladium(II) acetate (3.8 mg), triphenylphosphine (13 mg), potassium acetate (67 mg) and tetrabutylammonium bromide (55 mg) were added to a solution of the compound of Reference Example 45 (100 mg) in N,N-dimethylformamide (2 mL), and the resulting mixture was stirred at 80° C. for 4 hours. After the reaction mixture was cooled to 25° C., water was added thereto, followed by extraction with ethyl acetate. The organic phase was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (ethyl acetate) to obtain the title compound (40 mg) as a light-yellow amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.22-7.10 (m, 2H), 6.83-6.75 (s, 1H), 6.73-6.66 (m, 1H), 5.73 (d, J=17.0 Hz, 1H), 5.62 (d, J=17.0 Hz, 1H), 3.81-3.71 (m, 1H), 3.41-3.32 (m, 1H), 3.28-3.17 (m, 1H), 3.11-2.97 (m, 2H), 2.30 (s, 3H), 1.77-1.38 (m, 4H), 1.44 (s, 9H).  
      MS (ESI+) 472 (M + +1, 100%).  
     Reference Example 45  
     tert-Butyl {(3R)-1-[5-[(allylamino)carbonyl]-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Allylamine (260 μL) was added to a solution of the compound of Reference Example 173 (1.5 g), N,N-bis(2-oxo-3-oxazolidinyl)phosphinyl chloride (1.0 g) and triethylamine (1.3 mL) in dichloromethane (25 mL), and the resulting mixture was stirred at 25° C. for 2 hours. Water was added to the reaction mixture, followed by extraction with chloroform. The organic phase was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=1/1) to obtain the title compound (1.0 g) as a brown amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.38-7.31 (m, 1H), 7.23-7.13 (m, 2H), 6.79-6.69 (m, 1H), 5.88-5.75 (m, 1H), 5.55-5.40 (m, 2H), 5.21-5.08 (m, 2H), 3.96-3.90 (m, 2H), 3.80-3.68 (m, 1H), 3.40-3.28 (m, 1H), 2.95-2.79 (m, 3H), 1.80-1.45 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 600 (M + +1, 70%).  
     Reference Example 46  
     tert-Butyl [(3R)-1-[3-(2-chlorobenzyl)-6-{[methoxy(methyl)amino]carbonyl}-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      1-Hydroxybenzotriazole (251 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (316 mg), triethylamine (0.73 mL) and N,O-dimethylhydroxylamine hydrochloride (160 mg) were added to a solution of the compound of Reference Example 47 (456 mg) in N,N-dimethylformamide (10 mL), and the resulting mixture was stirred at 25° C. for 24 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to 0/1) to obtain the title compound (197 mg) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.36 (m, 1H), 7.24-7.12 (m, 2H), 6.71-6.65 (m, 1H), 6.65 (s, 1H), 5.77 (d, J=17.0 Hz, 1H), 5.62 (d, J=17.0 Hz, 1H), 3.85-3.73 (m, 1H), 3.61 (brs, 3H), 3.50 (s, 3H), 3.46-3.38 (m, 1H), 3.36 (s, 3H), 3.07-2.95 (m, 3H), 1.80-1.49 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 559 (M + +1, 55%).  
     Reference Example 47  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid  
     
       
         
         
             
             
         
       
     
      A solution consisting of the compound of Reference Example 13 (970 mg), 1N sodium hydroxide (4 mL) and ethanol (10 mL) was stirred at 80° C. for 1 hour. After the reaction mixture was concentrated under reduced pressure, a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (920 mg) as a white solid.  
      MS (ESI+) 516 (M + +1, 100%).  
     Reference Example 48  
     Ethyl 2-[(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (17 mg) was synthesized by the same process as in Reference Example 16. MS (ESI+) 530 (M + +1, 27%).  
     Reference Example 49  
     Isopropyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (50 mg) was synthesized by the same process as in Reference Example 16.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (s, 1H), 7.42-7.38 (m, 1H), 7.24-7.12 (m, 2H), 6.73-6.68(m, 1H), 5.80 (d, J=17.0 Hz, 1H), 5.65 (d, J=17.0 Hz, 1H), 5.30-5.20 (m, 1H), 3.83-3.72 (m, 1H), 3.45-3.35 (m, 1H), 3.08-2.92 (m, 3H), 1.82-1.45 (m, 4H), 1.43 (s, 9H), 1.39(s, 3H), 1.37 (s, 3H).  
      MS (ESI+) 544 (M + +1, 44%).  
     Reference Example 50  
     Benzyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (55 mg) was synthesized by the same process as in Reference Example 16.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.50 (s, 1H), 7.45-7.32 (m, 6H), 7.25-7.12 (m, 2H), 6.72-6.68 (m, 1H), 5.80 (d, J=17.0 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 5.38 (s, 2H), 3.82-3.70 (m, 1H), 3.45-3.35 (m, 1H), 3.08-2.95 (m, 3H), 1.82-1.49 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 592 (M + +1, 67%).  
     Reference Example 51  
     tert-Butyl {(3R)-1-[6-(aminocarbonyl)-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The compound of Reference Example 47 (150 mg) was dissolved in N,N-dimethylformamide (3 mL), followed by adding thereto 1-hydroxybenzotriazole (55 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (69 mg), triethylamine (0.18 mL) and ammonium chloride (21 mg), and the resulting mixture was stirred at 25° C. for 13 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=10/1) to obtain the title compound (83 mg) as a light-yellow amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.46-7.38 (m, 1H), 7.29-7.15 (m, 3H), 6.79-6.71 (m, 1H), 5.75 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 3.87-3.73 (m, 1H), 3.51-3.39 (m, 1H), 3.11-2.94 (m, 3H), 1.86-1.50 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 501 (M + +1, 50%).  
     Reference Example 52  
     tert-Butyl {(3R)-1-[6-(aminocarbonyl)-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (85 mg) was synthesized by the same process as in Reference Example 51.  
      MS (ESI+) 515 (M + +1, 100%).  
     Reference Example 53  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-6-[(dimethylamino)carbonyl]-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      N,N-bis(2-oxo-3-oxazolidinyl)-phosphinyl chloride (21 mg), triethylamine (29 μL) and dimethylamine hydrochloride (7.8 mg) were added to a solution of the compound of Reference Example 17 (28 mg) in dichloromethane (1 mL), and the resulting mixture was stirred at 25° C. for 2 hours. After the reaction, water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to isolation and purification by a preparative thin-layer silica gel chromatography (developing solvent: chloroform/methanol=10/1) to obtain the title compound (16 mg) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.38 (m, 1H), 7.25-7.13 (m, 2H), 6.87 (s, 1H), 6.79-6.71(m, 1H), 5.79 (d, J=17.0 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 3.84-3.71 (m, 1H), 3.49-3.39 (m, 1H), 3.20 (m, 6H), 3.10-2.91 (m, 3H), 1.83-1.50 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 529 (M + +1, 44%).  
     Reference Example 54  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-6-[(dimethylamino)carbonyl]-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      Potassium carbonate (3 mg) and methyl iodide (4 μL) were added to a solution of the compound of Reference Example 53 (11 mg) in N,N-dimethylformamide (0.5 mL), and the resulting mixture was stirred at 25° C. for 13 hours. After the reaction, water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (11 mg) as a light-yellow amorphous substance.  
      MS (ESI+) 543 (M + +1, 62%).  
     Reference Example 55  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (265 mg) was synthesized by the same process as in Reference Example 16.  
      MS (ESI+) 534 (M + +1, 75%).  
     Reference Example 56  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid  
     
       
         
         
             
             
         
       
     
      The title compound (907 mg) was synthesized by the same process as in Reference Example 17.  
      MS (ESI+) 520 (M + +1, 58%).  
     Reference Example 57  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(3-methylbut-2-en-1-yl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (680 mg) was synthesized by adopting the same process as in Reference Example 17 and then the same process as in Reference Example 16.  
      MS (ESI+) 460 (M + +1, 38%).  
     Reference Example 58  
     Ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-1-(2-chloro-5-fluorobenzyl)-4-iodo-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (3.3 g) was synthesized by the same process as in Reference Example 18.  
      MS (ESI+) 607 (M + +1, 30%).  
     Reference Example 59  
     Ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-4-iodo-1-(3-methylbut-2-en-1-yl)-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (2.8 g) was synthesized by the same process as in Reference Example 18.  
      MS (ESI+) 533 (M + +1, 33%).  
     Reference Example 60  
     Ethyl 4-amino-2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chloro-5-fluorobenzyl)-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      Sodium hydride (60%, 1.42 g) was added to tetrahydrofuran (260 mL) at room temperature and stirred for 30 minutes. A solution (110 mL) of ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]-N-(2-chloro-5-fluorobenzyl)glycinate (19.5 g) in tetrahydrofuran was added to the reaction solution at 0° C. and stirred at room temperature for 2 hours. The reaction solution was cooled to 0° C. and water (2.0 mL) was carefully added thereto, followed by adding thereto a saturated aqueous ammonium chloride solution (10 mL). The reaction solution was concentrated under reduced pressure and water and potassium carbonate were added to the residue to obtain an alkaline solution, followed by two runs of extraction with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound as a crude product (19.5 g).  
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33 (dd, J=5.0, 8.7 Hz, 1H), 6.90 (dt, J=3.0, 8.4 Hz, 1H), 6.54-6.52 (m, 1H), 5.21 (s, 2H), 5.12-4.97 (m, 3H), 4.15-4.10 (m, 2H), 3.79-3.70 (m, 1H), 3.30 (dd, J=3.2, 12.1 Hz, 1H), 2.99-2.91 (m, 1H), 2.90-2.82 (m, 2H), 1.79-1.51 (m, 4H), 1.41 (s, 9H), 1.10-1.05 (m, 3H).  
      MS (ESI+) 496 (M + +1, 100%).  
     Reference Example 61  
     Ethyl 4-amino-2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(3-methylbut-2-en-1-yl)-1H-imidazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      Sodium hydride (1.24 g, a 60% oil dispersion) was added to tetrahydrofuran (130 mL) at room temperature and stirred for 30 minutes. A solution (50 mL) of ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]-N-(3-methylbut-2-en-1-yl)glycinate (8.69 g) in tetrahydrofuran was added to the reaction solution at 0° C. and stirred at room temperature for 2 hours. The reaction solution was cooled to 0° C. and water (1.0 mL) was carefully added thereto, followed by adding thereto a saturated aqueous ammonium chloride solution (5 mL). The reaction solution was concentrated under reduced pressure and water and potassium carbonate were added to the residue to obtain an alkaline solution, followed by two runs of extraction with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (8.71 g) as a crude product.  
       1 H NMR (300 MHz, CDCl 3 ) δ 5.24-5.21 (m, 1H), 5.06-4.96 (m, 1H), 4.92-4.82 (m, 2H), 4.57-4.55 (m, 2H), 4.27 (q, J=7.1 Hz, 2H), 3.81-3.79 (m, 1H), 3.33-3.30 (m, 1H), 3.06-2.05 (m, 1H), 3.00-2.98 (m, 1H), 2.88 (dd, J=6.8, 12.0 Hz, 1H), 1.84-1.78 (m, 2H), 1.81-1.40 (m, 2H), 1.73 (s, 3H), 1.70 (s, 3H), 1.44 (s, 9H), 1.33 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 422 (M + +1, 100%).  
     Reference Example 62  
     Ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl](cyanoimino)methyl]-N-(2-chloro-5-fluorobenzyl)glycinate  
     
       
         
         
             
             
         
       
     
      2-Chloro-5-fluorobenzyl bromide (21.9 g) and potassium carbonate (27.6 g) were added to a solution (133 mL) of ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]glycinate (23.4 g) in acetonitrile at room temperature and stirred overnight. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1 to 2/3) to obtain the title compound (19.9 g).  
       1 H NMR (300 MHz, CDCl 3 ) δ 7.37 (dd, J=5.0, 8.8 Hz, 1H), 7.08-7.06, (m, 1H), 7.01 (dt, J=2.9, 8.3 Hz, 1H), 4.88-4.68 (m, 1H), 4.62-4.53 (m, 2H), 4.23 (q, J=7.1 Hz, 2H), 4.03-3.89 (m, 2H), 3.74-3.70 (m, 2H), 3.59-3.51 (m, 1H), 3.45-3.35 (m, 1H), 3.22-3.14 (m, 1H), 1.95-1.71 (m, 2H), 1.71-1.66 (m, 1H), 1.59-1.56 (m, 1H), 1.43 (s, 9H), 1.29 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 496 (M + +1, 52%).  
     Reference Example 63  
     Ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}(cyanoimino)methyl]-N-(3-methylbut-2-en-1-yl)glycinate  
     
       
         
         
             
             
         
       
     
      1-Bromo-3-methyl-2-butene (7.59 g) and potassium carbonate (14.1 g) were added to a solution (68 mL) of ethyl N-[(E)-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}(cyanoimino)methyl]glycinate (12.0 g) in acetonitrile at room temperature and stirred overnight. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1 to 1/2) to obtain the title compound (8.89 g).  
       1 H NMR (300 MHz, CDCl 3 ) δ 5.18-5.14 (m, 1H), 4.81 (brs, 1H), 4.20 (q, J=7.1 Hz, 2H), 4.03 (s, 2H), 3.91-3.89 (m, 2H), 3.69-3.67 (m, 2H), 3.55-3.50 (m, 1H), 3.40-3.30 (m, 1H), 3.20-3.15 (m, 1H), 1.94-1.86 (m, 2H), 1.74 (s, 3H), 1.64 (s, 3H), 1.81-1.40 (m, 2H), 1.44 (s, 9H), 1.27 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 422 (M + +1, 39%).  
     Reference Example 64  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-(hydroxymethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 47 (2.11 g) and triethylamine (0.68 mL) in tetrahydrofuran (20 mL) was cooled to 0° C., followed by adding dropwise thereto isopropyl chlorocarbonate (0.68 mL), and the resulting mixture was stirred at 0° C. for 1 hour. The precipitate formed was collected by filtration and washed with tetrahydrofuran, and the filtrate was cooled to 0° C. An aqueous solution (2 mL) of sodium tetrahydroborate (309 mg) was added dropwise thereto and the resulting mixture was stirred at 0° C. for 30 minutes. After the reaction, a saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1˜chloroform/methanol=10/1) to obtain the title compound (1.9 g) as a white amorphous substance.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.35 (m, 1H), 7.22-7.08 (m, 2H), 6.65-6.58 (m, 1H), 6.56(s, 1H), 5.74 (d, J=17.0 Hz, 1H), 5.60 (d, J=17.0 Hz, 1H), 4.61(s, 2H), 3.82-3.72 (m, 1H), 3.65 (s, 3H), 3.44-3.32 (m, 1H), 3.06-2.90 (m, 3H), 1.81-1.50 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 502 (M + +1, 100%).  
     Reference Example 65  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(3-methylbut-2-en-1-yl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridine-6-carboxylic acid  
     
       
         
         
             
             
         
       
     
      The title compound (590 mg) was synthesized by the same process as in Reference Example 47.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (s, 1H), 5.44-5.37 (m, 1H), 5.05-4.94 (m, 2H), 3.94-3.80(m, 1H), 3.60-3.51 (m, 1H), 3.33-3.05 (m, 3H), 1.97-1.65 (m, 4H), 1.81 (s, 3H), 1.75 (s, 3H), 1.44 (s, 9H).  
      MS (ESI+) 446 (M + +1, 35%).  
     Reference Example 66  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-(3-methoxyphenyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, molecular sieve 4A (400 mg, Wako Pure Chemical Industries, Ltd.), triethylamine (59 μL) and copper acetate (80 mg) were added to a solution of the compound of Reference Example 29 (100 mg) and 3-methoxyphenylboric acid (66 mg) in dichloromethane (5 mL), and the resulting mixture was stirred at room temperature for 21 hours. The reaction mixture was filtered through Celite, followed by washing with chloroform, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 to 0/1) to obtain the title compound (43 mg).  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.39-7.28 (m, 2H), 7.21-7.09 (m, 3H), 6.97-6.87 (m, 3H), 6.75-6.71 (m, 1H), 6.67 (d, J=7.3 Hz, 1H), 5.78 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 3.84-3.73 (m, 1H), 3.81 (s, 3H), 3.46-3.36 (m, 1H), 3.06-2.94 (m, 3H), 1.81-1.49(m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 564 (M + +1, 100%).  
     Reference Example 67  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-(3-fluorophenyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (36 mg) was synthesized by the same process as in Reference Example 66.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.49-7.32 (m, 2H), 7.20-7.02 (m, 6H), 6.77-6.73 (m, 1H), 6.70 (d, J=7.2 Hz, 1H), 5.76 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 3.85-3.70 (m, 1H), 3.45-3.36 (m, 1H), 3.07-2.92 (m, 3H), 1.80-1.52 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 552 (M + +1, 100%).  
     Reference Example 68  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-5-phenyl-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (73 mg) was synthesized by the same process as in Reference Example 66.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.48-7.41 (m, 2H), 7.40-7.32 (m, 4H), 7.24-7.10 (m, 3H), 6.80-6.72 (m, 1H), 6.68 (d, J=7.3 Hz, 1H), 5.78 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 3.85-3.74 (m, 1H), 3.48-3.38 (m, 1H), 3.10-2.95 (m, 3H), 1.82-1.57 (m, 3H), 1.43(s, 9H), 0.91-0.73 (m, 1H).  
      MS (ESI+) 534 (M + +1, 100%).  
     Reference Example 69  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-(4-fluorophenyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (58 mg) was synthesized by the same process as in Reference Example 66.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.40-7.33 (m, 3H), 7.18-7.11 (m, 5H), 6.77-6.71 (m, 1H), 6.69 (d, J=7.3 Hz, 1H), 5.76 (d, J=17.0 Hz, 1H), 5.61 (d, J=17.0 Hz, 1H), 3.83-3.76 (m, 1H), 3.48-3.40 (m, 1H), 3.08-3.01 (m, 3H), 1.77-1.64 (m, 3H), 1.42 (s, 9H), 0.85-0.80 (m, 1H).  
      MS (ESI+) 552 (M + +1, 100%).  
     Reference Example 70  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4-oxo-6-(phenoxymethyl)-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 73 (100 mg), cesium carbonate (163 mg) and phenol (25 mL) in N,N-dimethylformamide (3 mL) was stirred at 25° C. for 16 hours. After the reaction, water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (71 mg) as a white amorphous substance.  
      MS (ESI+) 578 (M + +1, 100%).  
     Reference Example 71  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-6-[(3-methoxyphenoxy)methyl]-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (57 mg) was obtained as a white amorphous substance by the same process as in Reference Example 70.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.37 (m, 1H), 7.26-7.15 (m, 3H), 6.75 (3, 1H), 6.74-6.68(m, 1H), 6.60-6.50 (m, 3H), 5.78 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 5.00 (3, 2H), 3.80 (s, 3H), 3.80-3.72 (m, 1H), 3.62 (s, 3H), 3.40-3.37 (m, 1H), 3.02-2.89 (m, 3H), 1.76-1.67 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 608 (M + +1, 100%).  
     Reference Example 72  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-(cyanomethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The compound of Reference Example 73 (200 mg), potassium cyanide (27 mg) and potassium iodide (3 mg) were dissolved in dimethylformamide (5 mL), and the resulting solution was stirred at 25° C. for 24 hours. After the reaction, water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate) to obtain the title compound (105 mg) as a brown amorphous substance.  
      MS (ESI+) 511 (M + +1, 100%).  
     Reference Example 73  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-6-(chloromethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]pyridin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Under a nitrogen atmosphere, N-chlorosuccinimide (339 mg) and triphenylphosphine (656 mg) were added to a solution (10 mL) of the compound of Reference Example 64 (501 mg) in tetrahydrofuran, and the resulting mixture was stirred at 25° C. for 2 hours. After the reaction, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (485 mg) as a light-yellow amorphous substance.  
      MS (ESI+) 520 (M + +1, 100%).  
     Reference Example 74  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      A solution of tetrakis(triphenylphosphine)-palladium(0) (20 mg), 2-aminobenzeneboric acid (23 mg) and sodium carbonate (36 mg) in water (0.7 mL) was added to a solution of the compound of Reference Example 18 (100 mg) in ethylene glycol dimethyl ether, and the resulting mixture was stirred at 80° C. After 6 hours, the reaction solution was allowed to cool and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in ethanol (2 mL), followed by adding thereto sodium ethoxide (1 mL) (a 21% ethanol solution), and the resulting mixture was stirred at 80° C. After 1 hour, the reaction solution was allowed to cool and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (57 mg) as a white solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.24-8.22 (m, 1H), 7.47-7.37 (m, 2H), 7.31-7.10 (m, 4H), 6.78-6.70 (m, 1H), 5.78 (d, J=17 Hz, 1H), 5.68 (d, J=17 Hz, 1H), 3.87-3.76 (m, 1H), 3.48-3.39 (m, 1H), 3.31-3.20 (m, 1H), 3.16-3.03 (m, 2H), 1.80-1.48 (m, 4H), 1.47 (s, 9H).  
      MS (ESI+) 508 (M + +1, 100%).  
     Reference Example 75  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylate  
     
       
         
         
             
             
         
       
     
      A solution of tetrakis(triphenylphosphine)-palladium(0) (129 mg), methyl 4-amino-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (344 mg) and sodium carbonate (240 mg) in water (4.7 mL) was added to a solution (9.4 mL) of ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazole-5-carboxylate (665 mg) in ethylene glycol dimethyl ether, and the resulting mixture was stirred at 80° C. After 18.5 hours, the reaction solution was allowed to cool and a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/2). The compound thus obtained was dissolved in ethanol (2 mL), followed by adding thereto sodium ethoxide (1 mL) (a 21% ethanol solution), and the resulting mixture was stirred at 80° C. After 1.5 hours, the reaction solution was allowed to cool and water was added thereto, followed by extraction with ethyl acetate. The extract solution was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a liquid chromatography to obtain the title compound (5.8 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.81 (d, J=1.5 Hz, 1H), 7.97 (dd, J=1.8, 8.4 Hz, 1H), 7.39 (dd, J=0.9, 7.9 Hz, 1H), 7.14-7.03 (m, 3H), 6.67 (d, J=7.9 Hz, 1H), 5.72 (d, J=16.8 Hz, 1H), 5.57 (d, J=16.8 Hz, 1H), 5.29 (m, 1H), 3.90 (s, 3H), 3.76-3.02 (m, 5H), 1.98-1.53 (m, 4H), 1.37 (s, 9H).  
      MS (ESI+) 566 (M + +1, 100%).  
     Reference Example 76  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-6-carboxylate  
     
       
         
         
             
             
         
       
     
      Palladium acetate (25 mg), triphenylphosphine (58 mg) and silver carbonate (59 mg) were added to a solution (10 mL) of methyl2[{[2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}(methyl)amino]benzoate (237 mg) in N,N-dimethylformamide, and the resulting mixture was stirred at 160° C. After one and a half hours, the reaction solution was allowed to cool and filtered through Celite, and a saturated aqueous sodium chloride solution was added to the filtrate, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1) to obtain the title compound (168 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.43 (dd, J=1.7, 7.9 Hz, 1H), 7.69 (dd, J=1.7, 7.5 Hz, 1H), 7.40 (dd, 1.5, 7.7 Hz, 1H), 7.32 (dd, J=7.5, 7.9 Hz, 1H), 7.23-7.12 (m, 2H), 6.72 (dd, J=1.3, 7.4 Hz, 1H), 6.19 (m, 1H), 5.76 (d, J=17.0 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 3.97 (s, 3H), 3.83 (brs, 1H), 3.57 (s, 3H), 3.44 (dd, J=3.3, 13.0 Hz, 1H), 3.29-3.24 (m, 1H), 3.10-3.09 (m, 2H), 1.83-1.51 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 580 (M + +1, 100%).  
      The compounds of Reference Examples 77 to 91 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 76.  
                                                                                                          Reference example       Reference example           number for starting       number   R 16     R 17     material               Reference Example 77   H   7-CO 2 (t-Bu)   Reference Example                   131       Reference Example 78   H   7-CO 2 Me   Reference Example                   133       Reference Example 79   H   8-CO 2 Me   Reference Example                   134       Reference Example 80   H   7,9-CO 2 Me   Reference Example                   135       Reference Example 81   H   6-MeO/7-CO 2 Et   Reference Example                   136       Reference Example 82   H   6,8-F/7-CO 2 Et   Reference Example                   137       Reference Example 83   F   8-CO 2 Me   Reference Example                   138       Reference Example 84   H   8-OCHF 2     Reference Example                   139       Reference Example 85   H   9-OMe/7-CO 2 (t-Bu)   Reference Example                   141       Reference Example 86   F   7-CO 2 (t-Bu)   Reference Example                   142       Reference Example 87   H   8-CH 2 CO 2 Et   Reference Example                   143       Reference Example 88   F   7-MeO/8-CO 2 Me   Reference Example                   144       Reference Example 89   F   6-MeO/8-CO 2 Me   Reference Example                   145       Reference Example 90   F   8-F/7-CO 2 (t-Bu)   Reference Example                   146       Reference Example 91   F   7,9-CO 2 Me   Reference Example                   132                  
 
     Reference Example 77  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.31 (d, J=8.3 Hz, 1H), 8.12 (d, J=1.1 Hz, 1H), 7.91 (dd, J=1.1, 8.3 Hz, 1H), 7.41 (dd, J=1.5, 7.9 Hz, 1H), 7.23-7.11 (m, 2H), 6.69 (d, J=6.2 Hz, 1H), 6.07-6.05 (m, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.66 (d, J=16.8 Hz, 1H), 3.79 (m, 1H), 3.79 (s, 3H), 3.45 (dd, J=3.5, 13.0 Hz, 1H), 3.27-3.21 (m, 1H), 3.09-3.07 (m, 2H), 1.74-1.52 (m, 4H), 1.65 (s, 9H), 1.47 (s, 9H).  
      MS (ESI+) 622 (M + +1, 100%).  
     Reference Example 78  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.35 (d, J=8.1 Hz, 1H), 8.16 (d, J=1.3 Hz, 1H), 7.97 (dd, J=1.3, 8.1 Hz, 1H), 7.41 (dd, J=1.5, 7.9 Hz, 1H), 7.23-7.10 (m, 2H), 6.68 (d, J=6.4 Hz, 1H), 6.11 (m, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.66 (d, J=16.8 Hz, 1H), 3.99 (s, 3H), 3.80 (s, 3H), 3.80-3.76 (m, 1H), 3.44 (dd, J=3.1, 12.6 Hz, 1H), 3.25-3.23 (m, 1H), 3.10-3.08 (m, 2H), 1.74-1.55 (4H, m), 1.47 (s, 9H). m, 3H), 1.83-1.53 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 580 (M + +1, 100%).  
     Reference Example 79  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.95 (d, J=2.0 Hz, 1H), 8.17 (dd, J=2.0, 8.8 Hz, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.41 (dd, J=1.3, 7.7 Hz, 1H), 7.23-7.11 (m, 2H), 6.70 (d, J=7.1 Hz, 1H), 5.78 (d, J=17.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 5.36-5.34 (m, 1H), 3.98 (s, 3H), 3.83 (brs, 1H), 3.76 (s, 3H), 3.46 (dd, J=3.1, 12.4 Hz, 1H), 3.26-3.16 (m, 1H), 3.10(m, 2H), 1.83-1.61 (m, 4H), 1.44 (s, 9H).  
      MS (ESI+) 580 (M + +1, 100%).  
     Reference Example 80  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.21 (d, J=1.3 Hz, 1H), 7.99 (brs, 1H), 7.41 (dd, J=1.5, 7.9 Hz, 1H), 7.24-7.13 (m, 2H), 6.72 (d, J=7.0 Hz, 1H), 5.81 (d, J=17.0 Hz, 1H), 5.65 (d, J=17.0 Hz, 1H), 4.66 (m, 1H), 4.04 (s, 3H), 3.99 (s, 3H), 3.81 (s, 3H), 3.75-3.73 (m, 1H), 3.45-3.42 (m, 1H), 3.10-2.98 (m, 3H), 1.76-1.51 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 638 (M + +1, 100%).  
     Reference Example 81  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.08 (d, J=8.2 Hz, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.41 (dd, J=7.9 and 1.3 Hz, 1H), 7.21 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.15 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.73 (d, J=7.9 Hz, 1H), 6.15 (brs, 1H), 5.78 (d, J=17.0 Hz, 1H), 5.64 (d, J=17.0 Hz, 1H), 4.44 (q, J=7.1 Hz, 2H), 3.93 (s, 3H), 3.81 (s, 1H), 3.79 (s, 3H), 3.43 (dd, J=12.0 and 3.3 Hz, 1H), 3.27-3.23 (m, 1H), 3.09-3.07 (m, 2H), 1.73 (brs, 2H), 1.56-1.50 (m, 2H), 1.46 (s, 9H), 1.45 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 624 (M + +1, 100%).  
     Reference Example 82  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (dd, J=8.8 and 1.6 Hz, 1H), 7.42 (dd, J=7.9 and 1.3 Hz, 1H), 7.24 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.15 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.69 (d, J=7.9 Hz, 1H), 6.06 (brs, 1H), 5.75 (d, J=16.5 Hz, 1H), 5.62 (d, J=16.5 Hz, 1H), 4.48 (q, J=7.1 Hz, 2H), 3.91-3.89 (m, 3H), 3.81 (brs, 1H), 3.43 (dd, J=12.1 and 3.4 Hz, 1H), 3.25-3.21 (m, 1H), 3.08 (brs, 3H), 1.74 (brs, 2H), 1.53 (brs, 1H), 1.46 (s, 9H), 1.43 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 630 (M + +1, 100%).  
     Reference Example 83  
       1 H NMR (400 MHz, CD 3 OD) δ 8.95 (s, 1H), 8.19 (m, 1H), 7.46 (m, 1H), 7.36 (m, 1H), 6.94 (m, 1H), 6.42 (m, 1H), 5.72-5.56 (m, 2H), 5.33 (bs, 1H), 4.03 (s, 3H), 3.93 (bs, 1H), 3.76 (s, 3H), 3.45 (m, 1H), 3.16-3.09 (m, 3H), 1.81-1.75 (m, 2H), 1.66-1.64 (m, 2H), 1.48 (s, 9H).  
      MS (ESI+) 598 (M + +1, 100%).  
     Reference Example 84  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.04 (m, 1H), 7.43-7.40 (m, 2H), 7.30 (dd, J=2.6, 9.2 Hz, 1H), 7.22-7.10 (m, 2H), 6.67 (d, J=7.7 Hz, 1H), 6.60 (t, J=73.8 Hz, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.67 (d, J=16.8 Hz, 1H), 3.81 (m, 1H), 3.73 (s, 3H), 3.46-3.42 (m, 1H), 3.21-3.18 (m, 1H), 3.10-3.08 (m, 1H), 1.74-1.59 (m, 4H), 1.45 (s, 9H).  
      MS (ESI+) 588 (M + +1, 100%).  
     Reference Example 85  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.77 (s, 1H), 7.45 (s, 1H), 7.41 (dd, J=7.9 and 1.3 Hz, 1H), 7.19 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.10 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.43 (d, J=7.9 Hz, 1H), 5.88 (d, J=16.5 Hz, 1H), 5.70 (d, J=16.5 Hz, 1H), 5.22 (d, J=7.9 Hz, 1H), 4.14 (s, 3H), 3.86 (brs, 1H), 3.79 (s, 3H), 3.47 (dd, J=12.1 and 3.4 Hz, 1H), 3.31-3.27 (m, 1H), 3.19-3.09 (m, 2H), 1.75-1.70 (m, 3H), 1.60 (s, 9H), 1.58-1.48 (m, 1H), 1.43 (s, 9H).  
      MS (ESI+) 652 (M + +1, 100%).  
     Reference Example 86  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, 1H, J=8.2 Hz), 8.13 (s, 1H), 7.91 (d, J=8.2 Hz, 1H), 7.40 (m, 1H), 6.92 (m, 1H), 6.43 (d, J=9.0 Hz, 1H), 6.01 (bs, 1H), 5.65-5.62 (m, 2H), 3.85 (m, 1H), 3.81 (s, 3H), 3.45 (m, 1H), 3.18-3.03 (m, 3H), 1.75-1.70 (m, 4H), 1.65 (s, 9H), 1.46 (s, 9H)  
      MS (ESI+) 640 (M + +1, 100%).  
     Reference Example 87  
       1 H NMR (300 MHz, CDCl 3 ) δ ppm 8.17 (d, J=2.0 Hz, 1H), 7.49-7.39 (m, 3H), 7.22-7.09 (m, 2H), 6.65 (d, J=7.1 Hz, 1H), 5.81 (d, J=17.9 Hz, 1H), 5.66 (d, J=17.9 Hz, 1H), 5.50-5.48 (m, 1H), 4.17 (dd, J=7.1, 14.3 Hz, 2H), 3.82-3.80 (m, 1H), 3.76 (s, 2H), 3.74 (s, 3H), 3.45-3.41 (m, 1H), 3.18-3.06 (m, 3H), 1.72-1.58 (m, 4H), 1.45 (s, 9H), 1.27 (d, J=7.1 Hz, 3H).  
      MS (ESI+) 608 (M + +1, 100%).  
     Reference Example 88  
      MS (ESI+) 628 (M + +1, 100%).  
     Reference Example 89  
       1 H NMR (300 MHz, CDCl 3 ) δ ppm 8.59 (d, J=1.8 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.37 (dd,J=5.1 and 8.8 Hz, 1H), 6.92 (td, J=3.1 and 8.3 Hz, 1H), 6.44 (dd, J=3.1 and 8.8 Hz, 1H), 5.65 (dd, J=17.2 and 38.3 Hz, 2H), 5.33 (d, J=6.8 Hz, 1H), 3.98 (s, 3H), 3.97 (s, 3H), 3.95 (s, 3H), 3.91-3.76 (m, 1H), 3.50-3.40 (m, 1H), 3.20-3.00 (m, 3H), 1.85-1.65 (m, 2H), 1.65-1.45 (m, 2H), 1.43 (s, 9H).  
      MS (ESI+) 628 (M + +1, 100%).  
     Reference Example 90  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.01-7.93 (m, 2H), 7.41-7.35 (m, 1H), 6.96-6.89 (m, 1H), 6.47-6.38 (m, 1H), 5.70 (d, J=17 Hz, 1H), 5.60 (d, J=17 Hz, 1H), 3.88-3.75 (m, 1H), 3.77 (s, 3H), 3.50-3.40 (m, 1H), 3.25-3.00 (m, 3H), 1.86-1.50 (m, 4H), 1.64 (s, 9H), 1.46 (s, 9H).  
      MS (ESI+) 658 (M + +1, 100%).  
     Reference Example 91  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.14 (d, J=1.3 Hz, 1H), 7.81 (d, J=1.3 Hz, 1H), 7.58 (dd, J=5.0, 9.3 Hz, 1H), 7.23-7.17 (m, 1H), 6.68 (dd, J=2.9, 9.3 Hz, 1H), 5.62 (d, J=17.4 HZ, 1H), 5.54 (d, J=17.4 Hz, 1H), 3.96 (s, 3H), 3.92 (s, 3H), 3.70 (s, 3H), 3.67-3.63 (m, 1H), 3.55-3.45 (m, 1H), 3.24-3.17 (m, 1H), 3.03-2.99 (m, 1H), 2.83-2.77 (m, 1H), 1.92-1.78 (m, 2H), 1.60-1.54 (m, 2H).  
      MS (ESI+) 556 (M + +1, 100%).  
     Reference Example 92  
     tert-Butyl {(3R)-1-[3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]-1,6-naphthylidin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (15 mg) was synthesized by the same process as in Reference Example 76.  
      MS (ESI+) 541 (M + +1, 100%).  
     Reference Example 93  
     Methyl 7-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-6-(2-chlorobenzyl)-2-(4-methoxybenzyl)-4-methyl-4-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (179 mg) was synthesized by the same process as in Reference Example 76.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.50 (d, J=8.6 Hz, 2H), 7.40 (dd, J=7.9 and 1.3 Hz, 1H), 7.20 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.14 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.83 (d, J=8.6 Hz, 2H), 6.73 (d, J=7.9 Hz, 1H), 5.93 (d, J=16.5 Hz, 1H), 5.86 (d, J=16.5 Hz, 1H), 5.81 (d, J=16.5 Hz, 1H), 5.71 (brd, J=4.9 Hz, 1H), 5.59 (d, J=16.5 Hz, 1H), 4.00 (s, 3H), 3.91 (brs, 1H), 3.86 (s, 3H), 3.76 (s, 3H), 3.47 (dd, J=12.0 and 3.3 Hz, 1H), 3.23-3.18 (m, 1H), 3.07 (brs, 2H), 1.74 (brs, 4H), 1.44 (s, 9H).  
      MS (ESI+) 690 (M + +1, 100%).  
     Reference Example 94  
     Methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-d]thieno[3,4-b]pyridine-6-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (238 mg) was synthesized by the same process as in Reference Example 76.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.05 (s, 1H), 7.40 (dd, J=1.5, 7.7 Hz, 1H), 7.23-7.11 (m, 2H), 6.68 (d, J=7.3 Hz, 1H), 5.72 (d, J=16.9 Hz, 1H), 5.60 (d, J=16.9 Hz, 1H), 5.39 (m, 1H), 3.91 (s, 3H), 3.82 (brs, 1H), 3.72 (s, 3H), 3.42 (dd, J=3.5, 12.5 Hz, 1H), 3.12-3.03 (m, 3H), 1.74-1.59 (m, 4H), 1.44 (s, 9H).  
      MS (ESI+) 586 (M + +1, 100%).  
     Reference Example 95  
     tert-Butyl {(3R)-1-[3-(2-chloro-5-fluorobenzyl)-5-methyl-4,6-dioxo-4,5,6,8-tetrahydro-3H-furo[3,4-b]imidazo[4,5-d]pyridin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      Palladium acetate (76 mg), triphenylphosphine (1688 mg) and silver carbonate (179 mg) were added to a solution (30 mL) of tert-butyl [(3R)-1-[1-(2-chloro-5-fluorobenzyl)-4-iodo-5-{[methyl(2-oxo-2,5-dihydrofuran-3-yl)amino]carbonyl}-1H-imidazo-2-yl]piperidin-3-yl]carbamate (722 mg) in N,N-dimethylformamide, and the resulting mixture was stirred at 160° C. After one and a half hours, the reaction solution was allowed to cool and filtered through Celite, and a saturated aqueous sodium chloride solution was added to the filtrate, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1) to obtain the title compound.  
     Reference Example 96  
     tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate  
     tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-9-carboxylate  
     
       
         
         
             
             
         
       
     
      Palladium acetate (10 mg), triphenylphosphine (23 mg) and sodium carbonate (24 mg) were added to a solution (10 mL) of tert-butyl 5-[{[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}(methyl)amino]-2-fluorobenzoate (112 mg) in dimethyl sulfoxide, and the resulting mixture was stirred with heating at 100° C. for 30 minutes. The solid was removed by filtration and the residue was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=4/1 to 2/1) to obtain the title compounds in amounts of 57 mg and 8 mg, respectively.  
      tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate:  1 H NMR (400 MHz, CDCl 3 ) δ 7.98-7.95 (m, 2H), 7.42 (dd, J=7.9 and 1.3 Hz, 1H), 7.21 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.14 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.69 (d, J=7.9 Hz, 1H), 6.10 (brs, 1H), 5.77 (d, J=16.5 Hz, 1H), 5.65 (d, J=16.5 Hz, 1H), 3.81 (brs, 1H), 3.76 (s, 3H), 3.43 (dd, J=12.1 and 3.4 Hz, 1H), 3.26-3.21 (m, 1H), 3.07 (brs, 3H), 1.74 (brs, 3H), 1.65 (s, 9H), 1.47 (s, 9H).  
      MS (ESI+) 640 (M + +1, 100%).  
      tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-3-(2-chlorobenzyl)-8-fluoro-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-9-carboxylate:  1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.39 (m, 2H), 7.24 (dd, J=7.9 and 1.3 Hz, 1H), 7.20 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.13 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.69 (d, J=7.9 Hz, 1H), 5.83 (d, J=16.5 Hz, 1H), 5.66 (d, J=16.5 Hz, 1H), 4.65 (d, J=6.6 Hz, 1H), 3.78 (brs, 1H), 3.73 (s, 3H), 3.38 (brs, 1H), 3.26-3.20 (m, 1H), 2.99 (brs, 3H), 1.71 (s, 9H), 1.66-1.63 (m, 3H), 1.43 (s, 9H).  
      MS (ESI+) 640 (M + +1, 100%).  
     Reference Example 97  
     tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-3-(5-fluoro-2-methylbenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate  
     
       
         
         
             
             
         
       
     
      2-Methyl-5-fluorobenzyl bromide (108 mg) and potassium carbonate (98 mg) were added to a solution (6 mL) of tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (177 mg) in N,N-dimethylformamide, and the resulting mixture was stirred at room temperature for 7 hours. After completion of the reaction, water was added to the reaction mixture, followed by extraction with ethyl acetate (100 mL). The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate/hexane=1/4 to 1/1) to obtain the title compound (62 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.31 (d, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.14 (d, J=5.8, 8.3 Hz, 1H), 6.86-6.80 (m, 1H), 6.25 (dd, J=2.4, 9.7 Hz, 1H), 5.99-5.97 (m, 1H), 5.63 (d, J=16.7 Hz, 1H), 5.48 (d, J=16.7 Hz, 1H), 3.82-3.78 (m, 1H), 3.78 (s, 3H), 3.45 (dd, J=3.2, 12.7 Hz, 1H), 3.19-3.11 (m, 3H), 2.39 (s, 3H), 1.86-1.55 (m, 4H), 1.65 (s, 9H), 1.46 (s, 9H).  
      MS (ESI+) 620 (M + +1, 100%).  
     Reference Example 98  
     2-[(3R)-3-(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid  
     
       
         
         
             
             
         
       
     
      Di-tert-butyl dicarbonate (420 mg) was added to a solution of 2-[(3R)-3-aminopiperidin-1-yl]-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid hydrochloride (830 mg) in a mixture of 1,4-dioxane (10 mL) and a saturated aqueous sodium hydrogencarbonate solution (10 mL), and the resulting mixture was stirred overnight at room temperature. The reaction solution was adjusted to pH 2 by pouring thereto a 10% aqueous potassium hydrogensulfate solution and was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (620 mg) as a white solid.  
      MS (ESI+) 584 (M + +1, 100%).  
     Reference Example 99  
     tert-Butyl {(3R)-1-[3-(2-chloro-5-fluorobenzyl)-7-cyano-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Trifluoroacetic anhydride (44 μL) was added dropwise to a solution of tert-butyl {(3R)-1-[7-(aminocarbonyl)-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate (44.2 mg) in tetrahydrofuran (1.1 mL), and the resulting mixture was stirred at room temperature for 2 hours. After the reaction, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in methanol (1.1 mL). Potassium carbonate (33.9 mg) and water (20 μL) were added thereto and the resulting mixture was stirred at room temperature. After 12 hours, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by a thin-layer chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (26.3 mg) as a white solid.  
      MS (ESI+) 547 (M + +1, 100%).  
     Reference Example 100  
     tert-Butyl {(3R)-1-[7-(aminocarbonyl)-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (71.8 mg) was synthesized by the same process as in Reference Example 51.  
      MS (ESI+) 565 (M + +1, 100%).  
     Reference Example 101  
     tert-Butyl {(3R)-1-[8-(aminocarbonyl)-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (13.5 mg) was synthesized by the same process as in Reference Example 51.  
      MS (ESI+) 565 (M + +1, 100%).  
     Reference Example 102  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-8-(morpholin-4-ylcarbonyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid (81.3 mg) was dissolved in N,N-dimethylformamide (1.2 mL), followed by adding thereto 1-hydroxybenzotriazole (35 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (47 mg), triethylamine (100 μL) and morpholine (19 μL), and the resulting mixture was stirred at 25° C. for 18 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (61.6 mg) as a white solid.  
      MS (ESI+) 635 (M + +1, 100%).  
     Reference Example 103  
     tert-Butyl((3R)-1-{3-(2-chlorobenzyl)-8-[(dimethylamino)carbonyl]-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid (82.4 mg) was dissolved in N,N-dimethylformamide (1.2 mL), followed by adding thereto 1-hydroxybenzotriazole (40 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (48 mg), triethylamine (102 μL) and a 40% aqueous dimethylamine solution (17 μL), and the resulting mixture was stirred at 25° C. for 15 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=10/1) to obtain the title compound (80.0 mg) as a white solid.  
      MS (ESI+) 593 (M + +1, 100%).  
     Reference Example 104  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-7-(methoxymethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      Sodium hydride (9 mg) was added to a solution of tert-butyl {(3R)-1-[3-(2-chlorobenzyl)-7-(hydroxymethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate (84.5 mg) in tetrahydrofuran (1.0 mL) at 0° C. and stirred for 20 minutes. Iodomethane (14 μL) was added dropwise thereto and the resulting mixture was stirred at room temperature for 18 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (72 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.28 (d, J=8.0 Hz, 1H), 7.43 (brs, 1H), 7.40 (dd, J=1.5, 8.0 Hz, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.22-7.09 (m, 2H), 6.68 (d, J=6.4 Hz, 1H), 6.27 (m, 1H), 5.77 (d, J=16.9 Hz, 1H), 5.66 (d, J=16.9 Hz, 1H), 4.62 (s, 2H), 3.81-3.69 (m, 1H), 3.75 (s, 3H), 3.46 (s, 3H), 3.44-3.40 (m, 1H), 3.27-3.22 (m, 1H), 3.09-3.07 (m, 2H), 1.73 (m, 4H), 1.47 (s, 9H).  
      MS (ESI+) 566 (M + +1, 100%).  
     Reference Example 105  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-7-(hydroxymethyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (86.5 mg) was synthesized by the same process as in Reference Example 64.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.22 (d, J=8.1 Hz, 1H), 7.41-7.39 (m, 2H), 7.28-7.26 (m, 1H), 7.22-7.09 (m, 2H), 6.67 (d, J=6.6 Hz, 1H), 6.14 (m, 1H), 5.76 (d, J=16.9 Hz, 1H), 5.64 (d, J=16.9 Hz, 1H), 4.83 (brs, 2H), 3.81 (m, 1H), 3.75-3.68 (m, 1H), 3.69 (s, 3H), 3.48-3.41 (m, 1H), 3.30-3.22 (m, 1H), 3.09-3.07 (m, 2H), 1.73-1.42 (m, 4H), 1.47 (s, 9H).  
      MS (ESI+) 552 (M + +1, 100%).  
     Reference Example 106  
     Ethyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate  
     
       
         
         
             
             
         
       
     
      1-Hydroxybenzotriazole (67 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (103 mg) and ethanol (0.5 mL) were added to a solution of 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid (125 mg) in N,N-dimethylformamide (2 mL), and the resulting mixture was stirred at 25° C. for 21 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1) to obtain the title compound (117 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.2 Hz, 1H), 8.16 (d, J=1.1 Hz, 1H), 7.98 (dd, J=1.1, 8.2 Hz, 1H), 7.41 (dd, J=1.3, 7.7 Hz, 1H), 7.24-7.11 (m, 2H), 6.69 (d, J=7.3 Hz, 1H), 6.11 (m, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.66 (d, J=16.8 Hz, 1H), 4.45 (dd, J=7.1, 14.1 Hz, 2H), 3.81 (s, 3H), 3.81-3.76 (m, 1H), 3.45 (dd, J=3.3, 12.7 Hz, 1H), 3.27-3.23 (m, 1H), 3.10-3.08 (m, 2H), 1.74-1.66 (4H, m), 1.47 (s, 9H), 1.46 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 594 (M + +1, 100%).  
      The compounds of Reference Examples 107 to 113 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 106.  
                                                                                              Refence example           Reference example number       number   R 16     R 17     for starting material                                   Reference Example 107   H                         Reference Example 120               Reference Example 108   H   CO 2 (i-Pr)   Reference Example 120       Reference Example 109   H   CO 2 (i-Bu)   Reference Example 120               Reference Example 110   H                         Reference Example 120               Reference Example 111   H   CO 2 CH(Me)CH(Me) 2     Reference Example 120               Reference Example 112   H                         Reference Example 120               Reference Example 113   H   CO 2 (CH 2 ) 3 OEt   Reference Example 120                  
 
     Reference Example 107  
      MS (ESI+) 679 (M + +1, 100%).  
     Reference Example 108  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J=8.2 Hz, 1H), 8.15 (d, J=1.1 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 7.41 (dd, J=1.1, 7.9 Hz, 1H), 7.27-7.12 (m, 2H), 6.69 (d, J=7.5 Hz, 1H), 6.06 (brs, 1H), 5.78 (d, J=16.9 Hz, 1H), 5.66 (d, J=16.9 Hz, 1H), 5.35-5.29 (m, 1H), 3.81 (s, 3H), 3.86-3.78 (m, 1H), 3.45 (dd, J=3.3, 12.8 Hz, 1H), 3.26-3.23 (m, 1H), 3.10-3.08 (m, 2H), 1.77-1.49 (m, 4H), 1.47 (s, 9H), 1.43 (d, J=6.3 Hz, 6H).  
      MS (ESI+) 608 (M + +1, 100%).  
     Reference Example 109  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.2 Hz, 1H), 8.17 (d, J=1.3 Hz, 1H), 7.98 (dd, J=1.3, 8.2 Hz, 1H), 7.41 (dd, J=1.5, 7.9 Hz, 1H), 7.23-7.11 (m, 2H), 6.69 (d, J=6.4 Hz, 1H), 6.08 (brd, J=6.9 Hz, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.66 (d, J=16.8 Hz, 1H), 4.17 (d, J=6.6 Hz, 2H), 3.80 (s, 3H), 3.80-3.76 (m, 1H), 3.44 (dd, J=3.3, 12.8 Hz, 1H), 3.23 (dd, J=4.2, 12.6 Hz, 1H), 3.10-3.08 (m, 2H), 1.74-1.69 (m, 4H), 1.47 (s, 9H), 1.06 (d, J=6.8 Hz, 6H).  
      MS (ESI+) 622 (M + +1, 100%).  
     Reference Example 110  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.2 Hz, 1H), 8.17 (d, J=1.3 Hz, 1H), 8.00 (d, J=8.2 Hz, 1H), 7.41 (dd, J=1.3, 8.1 Hz, 1H), 7.23-7.11 (m, 2H), 6.69 (d, J=7.3 Hz, 1H), 6.06 (m, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.66 (d, J=16.8 Hz, 1H), 4.47-4.42 (m, 1H), 4.38-4.32 (m, 2H), 4.04-3.83 (m, 1H), 3.80 (s, 3H), 3.68 (dd, J=3.3, 11.5 Hz, 1H), 3.54-3.42 (m, 2H), 3.25 (m, 1H), 3.08 (m, 2H), 2.14-1.63 (m, 8H), 1.47 (s, 9H).  
      MS (ESI+) 650 (M + +1, 100%).  
     Reference Example 111  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.2 Hz, 1H), 8.16 (d, J=1.1 Hz, 1H), 7.97 (d, J=8.2 Hz, 1H), 7.41 (dd, J=1.3, 8.0 Hz, 1H), 7.24-7.11 (m, 2H), 6.69 (d, J=6.6 Hz, 1H), 6.05 (m, 1H), 5.79 (d, J=17.0 Hz, 1H), 5.66 (d, J=17.0 Hz, 1H), 5.10-5.01 (m, 1H), 3.80 (s, 3H), 3.80 (m, 1H), 3.45 (dd, J=3.3, 12.8 Hz, 1H), 3.25-3.22 (m, 1H), 3.08 (m, 2H), 2.02-1.94 (m, 1H), 1.74 (m, 4H), 1.42 (s, 9H), 1.35 (d, J=6.2 Hz, 3H), 1.03 (dd, J=3.1, 6.8 Hz, 6H).  
      MS (ESI+) 636 (M + +1, 100%).  
     Reference Example 112  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.2 Hz, 1H), 8.17 (d, J=1.1 Hz, 1H), 8.01 (d, J=8.2 Hz, 1H), 7.41 (dd, J=1.5, 7.9 Hz, 1H), 7.24-7.11 (m, 2H), 6.69 (d, J=6.6 Hz, 1H), 6.05 (m, 1H), 5.79 (d, J=16.8 Hz, 1H), 5.65 (d, J=16.8 Hz, 1H), 4.23 (d, J=7.1 Hz, 2H), 3.81 (s, 3H), 3.81 (m, 1H), 3.45 (dd, J=3.3, 12.8 Hz, 1H), 3.27-3.23 (m, 1H), 3.10-3.08 (m, 2H), 1.74-1.42 (m, 3H), 1.47 (s, 9H), 1.37-1.24 (m, 2H), 0.69-0.63 (m, 2H), 0.49-0.39 (m, 2H).  
      MS (ESI+) 620 (M + +1, 100%).  
     Reference Example 113  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.1 Hz, 1H), 8.16 (d, J=1.3 Hz, 1H), 7.97 (dd, J=1.3, 8.1 Hz, 1H), 7.41 (dd, J=1.3, 7.9 Hz, 1H), 7.24-7.11 (m, 2H), 6.69 (d, J=6.2 Hz, 1H), 6.07 (m, 1H), 5.79 (d, J=17.0 Hz, 1H), 5.66 (d, J=17.0 Hz, 1H), 4.50 (t, J=6.4 Hz, 2H), 3.80-3.77 (m, 1H), 3.80 (s, 3H), 3.66-3.60 (m, 2H), 3.56-3.42 (m, 3H), 3.27-3.23 (m, 1H), 3.10-3.08 (m, 2H), 2.15-2.05 (m, 2H), 1.88-1.80 (m, 2H), 1.47 (s, 9H), 1.28-1.19 (m, 5H).  
      MS (ESI+) 652 (M + +1, 100%).  
     Reference Example 114  
     (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-[(3R)-3-(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate  
     
       
         
         
             
             
         
       
     
      Potassium carbonate (47 mg) and 4-(bromomethyl)-5-methyl-1,3-dioxol-2-one (43 mg) were added to a solution of 2-[(3R)-3-(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chloro-5-fluorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid (100 mg) in N,N-dimethylformamide (2 mL), and the resulting mixture was stirred overnight at room temperature. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1) to obtain the title compound (54 mg) as a light-yellow solid.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.94 (s, 1H), 8.18 (m, 1H), 7.49 (m, 1H), 7.38 (m, 1H), 6.95 (m, 1H), 6.44 (m, 1H), 5.72-5.57 (m, 2H), 5.15 (s, 2H), 4.42-4.39 (m, 2H), 3.81 (m, 1H), 3.76 (s, 3H), 3.46 (m, 1H), 3.12-3.07 (m, 3H), 2.28 (s, 3H), 1.69 (m, 1H), 1.42 (s, 9H)  
      MS (ESI+) 696 (M + +1, 100%).  
      The compounds of Reference Examples 115 to 119 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 114.  
                                                                                              Reference example           Reference example number       number   R 16     R 17     for starting material               Reference Example 115   H   t-BuC(O)OCH 2 O(O)C   Reference Example 120       Reference Example 116   F   EtOC(O)OCH(Me)O(O)C   Reference Example 98               Reference Example 117   F                         Reference Example 98               Reference Example 118   F   Me 2 N(CH 2 ) 2 O(O)C   Reference Example 98               Reference Example 119   F                         Reference Example 98                  
 
     Reference Example 115  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (m, 1H), 8.17 (s, 1H), 8.00 (m, 1H), 7.40 (m, 1H), 7.23-7.11 (m, 2H), 6.67, (m, 1H), 6.06 (s, 2H), 5.81-5.63 (m, 2H), 3.80 (s, 3H), δ 3.47 (m, 1H), 3.25 (m, 1H), 3.08-3.03 (m, 2H), 2.96 (s, 1H), 2.88 (s, 1H), 1.75-1.73 (m, 2H), 1.55 (m, 1H), 1.46 (s, 9H), 1.24 (s, 9H)  
      MS (ESI+) 680 (M + +1, 100%).  
     Reference Example 116  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.35 (m, 1H), 8.16 (s, 1H), 7.98 (m, 1H), 7.38 (m, 1H), 7.13 (m, 1H), 6.94 (m, 1H), 6.44 (m, 1H), 6.01 (bs, 1H), 5.73-5.58 (m, 2H), 4.26 (q, J=7.16 Hz, 2H), 3.85 (m, 1H), 3.80 (s, 3H), 3.46 (m, 1H), 3.25-3.05 (m, 3H), 1.82-1.95 (m, 2H), 1.78-1.76 (m, 3H), 1.59 (m, 1H), 1.46 (s, 9H), 1.33 (t, J=7.16 Hz, 3H)  
      MS (ESI+) 700 (M + +1, 100%).  
     Reference Example 117  
      MS (ESI+) 698.6 (M + +1, 100%).  
     Reference Example 118  
       1 H NMR (400 MHz, CD 3 OD) δ 8.34 (m, 1H), 8.17 (m, 1H), 7.98 (m, 1H), 7.36 (m, 1H), 6.92 (m, 1H), 6.43 (m, 1H), 6.04 (bs, 1H), 5.73-5.59 (m, 2H), 4.51 (t, J=5.84 Hz, 2H), 3.82 (m, 1H), 3.80 (s, 3H), 3.43 (m, 1H), 3.22-3.07 (m, 3H), 2.78 (t, J=5.84 Hz, 2H), 2.38 (s, 6H), 1.86-1.77 (m, 3H), 1.58 (m, 1H), 1.45 (s, 9H)  
      MS (ESI+) 655 (M + +1, 100%).  
     Reference Example 119  
       1 H NMR (400 MHz, CD 3 OD) δ 8.35 (m, 1H), 8.16 (s, 1H), 7.98 (m, 1H), 7.36 (m, 1H), 7.11 (m, 1H), 6.94 (m, 1H), 6.42 (m, 1H), 6.03 (bs, 1H), 5.69-5.63 (m, 2H), 4.66 (m, 1H), 3.85 (m, 1H), 3.81 (s, 3H), 3.44 (m, 1H), 3.28-3.08 (m, 3H), 1.95-1.93 (m, 2H), 1.77-1.73 (m, 4H), 1.70-1.68 (m, 3H), 1.61-1.53 (m, 4H), 1.46 (s, 9H), 1.41-1.26 (m, 4H)  
      MS (ESI+) 754 (M + +1, 100%).  
     Reference Example 120  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylic acid  
     
       
         
         
             
             
         
       
     
      A solution consisting of methyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (313 mg), 2N sodium hydroxide (4 mL) and ethanol (7 mL) was stirred at 80° C. for 2 hours. After the reaction mixture was concentrated under reduced pressure, a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (247 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.34 (d, J=8.3 Hz, 1H), 8.17 (brs, 1H), 8.01 (dd, J=1.3, 8.3 Hz, 1H), 7.41 (dd, J=1.3, 7.7 Hz, 1H), 7.28-7.11 (m, 2H), 6.71 (dd, J=1.5, 7.5 Hz, 1H), 6.01 (d, J=7.0 Hz, 1H), 5.79 (d, J=17.0 Hz, 1H), 5.67 (d, J=17.0 Hz, 1H), 3.79 (s, 3H), 3.79 (m, 1H), 3.49 (dd, J=3.3, 12.6 Hz, 1H), 3.23 (dd, J=5.5, 12.4 Hz, 1H), 3.09 (m, 2H), 1.76-1.58 (m, 4H), 1.48 (s, 9H).  
      MS (ESI+) 566 (M + +1, 100%).  
      The compounds of Reference Examples 121 to 128 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 120.  
                                                                                                          Reference example       Reference example           number for starting       number   R 16     R 17     material               Reference Example 121   H   8-CO 2 H   Reference Example 79       Reference Example 122   F   8-CO 2 H   Reference Example 83       Reference Example 123   H   6-CO 2 H   Reference Example 76       Reference Example 124   H   7,9-CO 2 H   Reference Example 80       Reference Example 125   H   8-CH 2 CO 2 H   Reference Example 87       Reference Example 126   F   7-MeO/   Reference Example 88               8-CO 2 H       Reference Example 127   F   6-MeO/   Reference Example 89               8-CO 2 H       Reference Example 128   F   7,9-CO 2 H   Reference Example 91                  
 
     Reference Example 121  
       1 H NMR (300 MHz, CDCl 3 ) δ 9.49 (brs, 1H), 8.21 (d, J=2.9 Hz, 1H), 7.48-7.42 (m, 2H), 7.26-7.13 (m, 2H), 6.72 (d, J=7.1 Hz, 1H), 5.85 (d, J=16.7 Hz, 1H), 5.70 (d, J=16.7 Hz, 1H), 4.94 (m, 1H), 3.85 (brs, 1H), 3.76 (s, 3H), 3.71-3.67 (m, 1H), 3.31-3.23 (m, 3H), 1.92 (brs, 1H), 1.69-1.63 (m, 3H), 1.43 (s, 9H).  
      MS (ESI+) 566 (M + +1, 100%).  
     Reference Example 122  
      337  
       1 H NMR (400 MHz, CDCl 3 ) δ 9.49 (s, 1H), 8.25 (m, 1H), 7.52 (m, 1H), 7.40 (m, 1H), 6.95 (m, 1H), 6.46 (m, 1H), 5.80-5.64 (m, 2H), 4.91 (bs, 1H), 3.86 (bs, 1H), 3.78 (s, 3H), 3.65 (m, 1H), 3.25 (s, 3H), 1.93 (m, 1H), 1.79 (m, 1H), 1.70 (m, 1H), 1.59 (m, 1H), 1.42 (s, 9H).  
      MS (ESI+) 584 (M + +1, 100%).  
     Reference Example 123  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.36 (d, J=7.9 Hz, 1H), 7.72 (m, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.26-7.04 (m, 3H), 6.67 (d, J=7.3 Hz, 1H), 6.08 (m, 1H), 5.68 (d, J=17.0 Hz, 1H), 5.55 (d, J=17.0 Hz, 1H), 3.82 (m, 1H), 3.60 (s, 3H), 3.51-3.44 (m, 1H), 3.25-3.22 (m, 2H), 3.07 (m, 1H), 1.73-1.46 (m, 4H), 1.46 (s, 9H).  
      MS (ESI+) 566 (M + +1, 100%).  
     Reference Example 124  
      MS (ESI+) 610 (M + +1, 100%).  
     Reference Example 125  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.25 (s, 1H), 7.49-7.37 (m, 3H), 7.18-7.10 (m, 2H), 6.61 (d, J=7.9 Hz, 1H), 5.77 (d, J=16.7 Hz, 1H), 5.63 (d, J=16.7 Hz, 1H), 5.22-5.19 (m, 1H), 3.80 (s, 2H), 3.77-3.73 (m, 1H), 3.71 (s, 3H), 3.46-3.42 (m, 1H), 3.09-3.03 (m, 3H), 1.74-1.60 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 580 (M + +1, 100%).  
     Reference Example 126  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.44 (s, 1H), 7.54 (dd, J=5.0 and 8.6 Hz, 1H), 7.16 (td, J=2.9 and 8.4 Hz, 1H), 7.03 (s, 1H), 6.90 (d, J=7.7 Hz, 1H), 6.58 (dd, J=2.6 and 9.3 Hz, 1H), 5.46 (dd, J=17.9 and 21.6 Hz, 2H), 3.96 (s, 3H), 3.63 (s, 3H), 3.55-3.20 (m, 3H), 2.90-2.78 (m, 1H), 2.76-2.64 (m, 1H), 1.80-1.60 (m, 2H), 1.60-1.40 (m, 2H), 1.31 (s, 9H).  
      MS (ESI+) 614 (M + +1, 100%).  
     Reference Example 127  
       1 H NMR (300 MHz, DMSO-d 6 ) δ 8.33 (d, J=1.8 Hz, 1H), 7.57 (d, J=1.8 Hz, 1H), 7.53 (dd, J=5.1 and 8.8 Hz, 1H), 7.15 (td, J=2.9 and 8.4 Hz, 1H), 6.89 (d, J=7.7 Hz, 1H), 6.62 (dd, J=2.9 and 8.8 Hz, 1H), 5.48 (dd, J=17.6 and 22.3 Hz, 2H), 3.93 (s, 3H), 3.79 (s, 3H), 3.55-3.20 (m, 3H), 2.90-2.78 (m, 1H), 2.76-2.64 (m, 1H), 1.80-1.60 (m, 2H), 1.60-1.40 (m, 2H), 1.25 (s, 9H).  
      MS (ESI+) 614 (M + +1, 100%).  
     Reference Example 128  
      MS (ESI+) 628 (M + +1, 100%).  
     Reference Example 129  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-d]thieno[3,4-b]pyridine-6-carboxylic acid  
     
       
         
         
             
             
         
       
     
      The title compound (120 mg) was obtained by the same process as in Reference Example 120.  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.11 (s, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.22-7.12 (m, 2H), 6.71 (d, J=7.3 Hz, 1H), 5.73 (d, J=16.7 Hz, 1H), 5.59 (d, J=16.7 Hz, 1H), 5.24 (d, J=7.0 Hz, 1H), 3.82 (m, 1H), 3.74 (s, 3H), 3.51-3.48 (m, 1H), 3.06 (m, 3H), 1.80-1.44 (m, 4H), 1.44 (s, 9H).  
      MS (ESI+) 572 (M + +1, 100%).  
     Reference Example 130  
     Methyl 2-[{[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}(methyl)amino]benzoate  
     
       
         
         
             
             
         
       
     
      Potassium carbonate (227 mg) and methyl iodide (95 μL) were added to a solution of methyl 2-({[2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}amino)benzoate (425 mg) in N,N-dimethylformamide (4 mL), and the resulting mixture was stirred at 25° C. for 86 hours. After the reaction, a saturated aqueous sodium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate/hexane=1/3) to obtain the title compound (237 mg) as a white solid.  
      MS (ESI+) 708 (M + +1, 100%).  
      The compounds of Reference Examples 131 to 146 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 130.  
                                                                                                          Reference example       Reference example           number for starting       number   R 16     R 17     material               Refence Example 131   H   7-CO 2 (t-Bu)   Refence Example 153       Refence Example 132   F   7,9-CO 2 Me   Refence Example 154       Refence Example 133   H   7-CO 2 Me   Refence Example 155       Refence Example 134   H   8-CO 2 Me   Refence Example 156       Refence Example 135   H   7,9-CO 2 Me   Refence Example 157       Refence Example 136   H   6-MeO/7-CO 2 Et   Refence Example 158       Refence Example 137   H   6,8-F/7-CO 2 Et   Refence Example 159       Refence Example 138   F   8-CO 2 Me   Refence Example 160       Refence Example 139   H   8-OCHF 2     Refence Example 161       Refence Example 140   H   8-F/7-CO 2 (t-Bu)   Refence Example 162       Refence Example 141   H   9-OMe/   Refence Example 163               7-CO 2 (t-Bu)       Refence Example 142   F   7-CO 2 (t-Bu)   Refence Example 168       Refence Example 143   H   8-CH 2 CO 2 Et   Refence Example 164       Refence Example 144   F   7-MeO/8-CO 2 Me   Refence Example 165       Refence Example 145   F   6-MeO/8-CO 2 Me   Refence Example 166       Refence Example 146   F   8-F/7-CO 2 (t-Bu)   Refence Example 167                  
 
     Reference Example 131  
      MS (ESI+) 750 (M + +1, 100%).  
     Reference Example 132  
      MS (ESI+) 784 (M + +1, 100%).  
     Reference Example 133  
      MS (ESI+) 708 (M + +1, 100%).  
     Reference Example 134  
      MS (ESI+) 708 (M + +1, 100%).  
     Reference Example 135  
      MS (ESI+) 766 (M + +1, 100%).  
     Reference Example 136  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (brs, 1H), 7.42-7.40 (m, 1H), 7.31-7.21 (m, 3H), 7.17-7.13 (m, 1H), 6.92 (brs, 1H), 5.26 (brs, 2H), 5.02 (brs, 1H), 4.34 (q, J=7.1 Hz, 2H), 3.66 (brs, 4H), 3.29 (brs, 4H), 2.90 (brs, 3H), 1.77 (brs, 2H), 1.51 (brs, 2H), 1.42 (s, 9H), 1.26 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 752 (M + +1, 100%).  
     Reference Example 137  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.42 (d, J=7.9 Hz, 1H), 7.32-7.21 (m, 3H), 7.14 (brs, 1H), 6.82 (brs, 1H), 5.22 (brs, 2H), 4.91 (brs, 1H), 4.40 (q, J=7.1 Hz, 2H), 3.80 (brs, 1H), 3.32 (brs, 1H), 3.15 (brs, 3H), 2.99 (brs, 2H), 2.88 (brs, 2H), 1.78 (brs, 2H), 1.69-1.50 (m, 2H), 1.42 (s, 9H), 1.38 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 758 (M + +1, 100%).  
     Reference Example 138  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.90-7.84 (m, 2H), 7.42 (m, 1H), 7.03 (m, 1H), 6.95 (m, 1H), 6.70-6.68 (m, 2H), 5.20 (brs, 2H), 4.93 (brs, 1H), 3.90 (s, 3H), 3.79 (brs, 1H), 3.32 (m, 1H), 3.26 (s, 3H), 2.99 (m, 2H), 2.83 (m, 2H), 1.81 (m, 1H), 1.65-1.62 (m, 1H), 1.46 (s, 9H).  
      MS (ESI+) 726 (M + +1, 100%).  
     Reference Example 139  
      MS (ESI+) 716 (M + +1, 100%).  
     Reference Example 140  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.55-7.53 (m, 1H), 7.44-7.42 (m, 1H), 7.35-7.29 (m, 3H), 7.20 (brs, 1H), 6.97 (brs, 1H), 5.28 (brs, 1H), 5.07 (brs, 1H), 4.89 (brs, 1H), 3.81 (brs, 1H), 3.35-3.32 (m, 1H), 3.11 (brs, 3H), 3.01 (brs, 3H), 2.89 (brs, 1H), 1.80 (brs, 3H), 1.59 (s, 9H), 1.42 (s, 9H).  
      MS (ESI+) 768 (M + +1, 100%).  
     Reference Example 141  
       1 H NMR (400 MHz, CD 3 OD) δ 7.42-7.37 (m, 2H), 7.34-7.25 (m, 3H), 7.14 (brs, 1H), 6.64 (brs, 1H), 5.20-4.81 (m, 3H), 3.81-3.75 (m, 4H), 3.28 (brs, 1H), 3.12 (brs, 3H), 2.96-2.78 (m, 3H), 1.77 (brs, 3H), 1.59 (s, 9H), 1.54-1.49 (m, 1H), 1.42 (s, 9H).  
      MS (ESI+) 780 (M + +1, 100%).  
     Reference Example 142  
      MS (ESI+) 768 (M + +1, 100%).  
     Reference Example 143  
       1 H NMR (400 MHz, CD 3 OD) δ 8.17 (d, J=2.0 Hz, 1H), 7.49-7.39 (m, 3H), 7.22-7.09 (m, 2H), 6.65 (d, J=7.1 Hz, 1H), 5.81 (d, J=17.9 Hz, 1H), 5.66 (d, J=17.9 Hz, 1H), 5.50-5.48 (m, 1H), 4.17 (dd, J=7.1, 14.3 Hz, 2H), 3.82-3.80 (m, 1H), 3.76 (s, 2H), 3.74 (s, 3H), 3.45-3.41 (m, 1H), 3.18-3.06 (m, 3H), 1.72-1.58 (m, 4H), 1.45 (s, 9H), 1.27 (d, J=7.1 Hz, 3H).  
      MS (ESI+) 608 (M + +1, 100%).  
     Reference Example 144  
      MS (ESI+) 756 (M + +1, 100%).  
     Reference Example 145  
      MS (ESI+) 756 (M + +1, 100%).  
     Reference Example 146  
      MS (ESI+) 786 (M++1, 100%).  
     Reference Example 147  
     tert-Butyl [(3R)-1-(1-(2-chloro-5-fluorobenzyl)-4-iodo-5-{[methyl(pyridin-4-yl)amino]carbonyl}-1H-imidazol-2-yl)piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      A solution of the compound of Reference Example 169 (250 mg), potassium carbonate (68 mg) and methyl iodide (28 μL) in N,N-dimethylformamide (1 mL) was stirred at 25° C. for 3 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1→1/2) to obtain the title compound (80 mg) as a colorless amorphous substance.  
      MS (ESI+) 669 (M + +1, 100%).  
     Reference Example 148  
     Methyl 4-[{[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}(methyl)amino]-1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (265 mg) was synthesized by the same process as in Reference Example 147.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.25-7.12 (m, 6H), 6.92 (d, J=8.6 Hz, 2H), 6.81 (brs, 1H), 5.17 (bs, 4H), 4.82 (brs, 1H), 3.87-3.72 (m, 10H), 3.22-2.82 (m, 4H), 1.70-1.47 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 818 (M + +1, 100%).  
     Reference Example 149  
     Methyl 3-[{[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}(methyl)amino]thiophene-2-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (526 mg) was synthesized by the same process as in Reference Example 147.  
      MS (ESI+) 714 (M + +1, 100%).  
     Reference Example 150  
     tert-Butyl [(3R)-1-[1-(2-chloro-5-fluorobenzyl)-4-iodo-5-{[methyl(2-oxo-2,5-dihydrofuran-3-yl)amino]carbonyl}-1H-imidazo-2-yl]piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      A solution of tert-butyl [(3R)-1-[1-(2-chloro-5-fluorobenzyl)-4-iodo-5-{[(2-oxo-2,5-dihydrofuran-3-yl)-amino]carbonyl}-1H-imidazo-2-yl]piperidin-3-yl]carbamate (750 mg), potassium carbonate (204 mg) and methyl iodide (84 μL) in N,N-dimethylformamide (5 mL) was stirred at 25° C. for 3 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic phase was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=2/1→1/2) to obtain the title compound.  
     Reference Example 151  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (16.5 mg) was synthesized by the same process as in Reference Example 147.  
      MS (ESI+) 522 (M + +1, 100%).  
     Reference Example 152  
     Methyl 2-({[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}amino)benzoate  
     
       
         
         
             
             
         
       
     
      N,N-dimethylformamide (three drops) and oxalyl chloride (0.31 ml) were added to a solution of 2-[(3R)-3-(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazole-5-carboxylic acid (1.04 g) in dichloromethane (35 mL) at 0° C. After the resulting mixture was stirred at 25° C. for 4 hours, the solvent was distilled off by concentration under reduced pressure. Toluene (20 mL), diisopropylethylamine (0.64 mL) and methyl anthranilate (0.36 mL) were added to the residue and the resulting mixture was stirred at 120° C. for 8 hours. After the reaction solution was allowed to cool, a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=5/1→1/1) to obtain the title compound (425 mg) as a white solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ 11.26 (s, 1H), 8.45 (dd, J=1.1, 8.4 Hz, 1H), 8.02 (dd, J=1.7, 8.1 Hz, 1H), 7.51 (ddd, 1.7, 7.6, 8.4 Hz, 1H), 7.34-7.31 (m, 1H), 7.17-7.08 (m, 3H), 6.82-6.79 (m, 1H), 5.46 (d, J=16.5 Hz, 1H), 5.39 (d, J=16.5 Hz, 1H), 4.92 (m, 1H), 3.93 (s, 3H), 3.75 (brs, 1H), 3.27 (dd, J=3.3, 11.9 Hz, 1H), 2.90-2.86 (m, 3H), 1.71-1.52 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 694 (M + +1, 100%).  
      The compounds of Reference Examples 153 to 168 were synthesized from corresponding compounds of Reference Examples, respectively, by the same process as in Reference Example 152.  
                                                                                                          Reference example       Reference example           number for starting       number   R 16     R 17     material               Reference Example 153   H   7-CO 2 (t-Bu)   Reference Example 173       Reference Example 154   F   7,9-CO 2 Me   Reference Example 174       Reference Example 155   H   7-CO 2 Me   Reference Example 173       Reference Example 156   H   8-CO 2 Me   Reference Example 173       Reference Example 157   H   7,9-CO 2 Me   Reference Example 173       Reference Example 158   H   6-MeO/   Reference Example 173               7-CO 2 Et       Reference Example 159   H   6,8-F/   Reference Example 173               7-CO 2 Et       Reference Example 160   F   8-CO 2 Me   Reference Example 174       Reference Example 161   H   8-OCHF 2     Reference Example 173       Reference Example 162   H   8-F/   Reference Example 173               7-CO 2 (t-Bu)       Reference Example 163   H   9-OMe/   Reference Example 173               7-CO 2 (t-Bu)       Reference Example 164   H   8-   Reference Example 173               CH 2 CO 2 Et       Reference Example 165   F   7-MeO/   Reference Example 174               8-CO 2 Me       Reference Example 166   F   6-MeO/   Reference Example 174               8-CO 2 Me       Reference Example 167   F   8-F/   Reference Example 174               7-CO 2 (t-Bu)       Reference Example 168   F   8-CO 2 (t-Bu)   Reference Example 174                  
 
     Reference Example 153  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.16 (brs, 1H), 7.92-7.88 (m, 2H), 7.75-7.71 (m, 1H), 7.40-7.35 (m, 2H), 7.22-7.13 (m, 2H), 6.82-6.79 (m, 1H), 5.58 (d, J=15.9 Hz, 1H), δ 5.49 (d, J=15.9 Hz, 1H), 4.91 (m, 1H), 3.77 (brs, 1H), 3.30 (dd, J=3.3, 12.1 Hz, 1H), 2.90-2.84 (m, 3H), 1.80-1.59 (m, 4H), 1.59 (s, 9H), 1.43 (s, 9H).  
      MS (ESI+) 736 (M + +1, 100%).  
     Reference Example 154  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.46-8.37 (m, 3H), 7.34 (dd, J=5.1, 8.8 Hz, 1H), 6.95-6.89 (m, 1H), 6.52 (dd, 2.4, 8.8 Hz, 1H), 5.57 (d, J=16.3 Hz, 1H), 5.49 (d, 16.3 Hz, 1H), 4.87 (brd, J=7.5 Hz, 1H), 3.95 (s, 6H), 3.76 (brs, 1H), 3.31 (dd, J=2.9, 11.7 Hz, 1H), 2.94-2.81 (m, 3H), 1.83-1.64 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 770 (M + +1, 100%).  
     Reference Example 155  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.19 (brs, 1H), 8.03-8.02 (m, 1H), 7.89-7.86 (m, 1H), 7.81-7.78 (m, 1H), 7.43-7.35 (m, 2H), 7.22-7.13 (m, 2H), 6.82-6.79 (m, 1H), 5.58 (d, J=16.1 Hz, 1H), 5.51 (d, J=16.1 Hz, 1H), 4.93-4.90 (m, 1H), 3.92 (s, 3H), 3.76 (brs, 1H), 3.30 (dd, J=3.3, 12.1 Hz, 1H), 2.93-2.84 (m, 3H), 1.83-1.53 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 694 (M + +1, 100%).  
     Reference Example 156  
      H NMR (300 MHz, CDCl 3 ) δ 8.30 (brs, 1H), 8.05-7.97 (m, 2H), 7.65-7.60 (m, 2H), 7.38-7.35 (m, 1H), 7.21-7.08 (m, 2H), 6.81-6.79 (m, 1H), 5.58 (d, J=16.3 Hz, 1H), 5.50 (d, J=16.3 Hz, 1H), 4.91 (m, 1H), 3.93-3.91 (m, 1H), 3.90 (s, 3H), 3.76 (brs, 1H), 3.30 (d, J=9.2 Hz, 1H), 2.94-2.83 (m, 2H), 1.83-1.74 (m, 2H), 1.55-1.52 (m, 2H), 1.43 (s, 9H).  
      MS (ESI+) 694 (M + +1, 100%).  
     Reference Example 157  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.44 (s, 1H), 8.35 (m, 2H), 8.27 (brs, 1H), 7.38-7.35 (m, 1H), 7.20-7.15 (m, 2H), 6.83-6.80 (m, 1H), 5.59 (d, J=16.3 Hz, 1H), 5.51 (d, J=16.3 Hz, 1H), 4.89-4.86 (m, 1H), 3.94 (s, 6H), 3.76 (m, 1H), 3.31 (dd, J=3.5, 12.2 Hz, 1H), 2.94-2.84 (m, 3H), 1.79-1.56 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 752 (M + +1,000%).  
     Reference Example 158  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.94 (brs, 1H), 8.46 (dd, J=7.9 and 1.7 Hz, 1H), 7.56 (dd, J=7.9 and 1.7 Hz, 1H), 7.36 (dd, J=7.6 and 2.1 Hz, 1H), 7.21-7.14 (m, 2H), 7.11 (dd, J=7.9 and 7.9 Hz, 1H), 6.78 (dd, J=7.6 and 2.1 Hz, 1H), 5.60 (d, J=16.3 Hz, 1H), 5.53 (d, J=16.3 Hz, 1H), 4.94 (d, J=7.6 Hz, 1H), 4.40 (q, J=7.1 Hz, 2H), 3.91 (s, 3H), 3.77 (brs, 1H), 3.30 (dd, J=12.0 and 3.3 Hz, 1H), 2.94-2.87 (m, 3H), 1.76-1.63 (m, 2H), 1.59-1.48 (m, 2H), 1.43 (s, 9H), 1.41 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 738 (M + +1, 100%).  
     Reference Example 159  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.43 (brs, 1H), 8.35-8.29 (m, 1H), 7.37 (dd, J=7.9 and 1.3 Hz, 1H), 7.22-7.15 (m, 2H), 6.90 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.75 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 5.58 (d, J=16.5 Hz, 1H), 5.51 (d, J=16.5 Hz, 1H), 4.92 (d, J=7.9 Hz, 1H), 4.43 (q, J=7.1 Hz, 2H), 3.77 (brs, 1H), 3.31 (dd, J=12.1 and 3.4 Hz, 1H), 2.96-2.84 (m, 3H), 1.78-1.65 (m, 1H), 1.55-1.47 (m, 3H), 1.43 (s, 9H), 1.42 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 744 (M + +1, 100%).  
     Reference Example 160  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.41 (s, 1H), 8.02-7.99 (m, 2H), 7.64-7.58 (m, 2H), 7.34 (m, 1H), 6.93 (m, 1H), 6.50 (m, 1H), 5.53-5.46 (m, 2H), 4.85 (m, 1H), 3.91 (s, 3H), 3.76 (m, 1H), 3.31 (m, 1H), 2.99-2.81 (m, 3H), 1.80 (m, 1H), 1.68-1.58 (m, 3H), 1.42 (s, 9H).  
      MS (ESI+) 712 (M + +1, 100%).  
     Reference Example 161  
       1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (brs, 1H), 7.53-7.50 (m, 2H), 7.38-7.35 (m, 1H), 7.21-7.13 (m, 2H), 7.10-7.07 (m, 2H), 6.82-6.78 (m, 1H), 6.45 (t, J=73.8 Hz, 1H), 5.67 (d, J=16.5 Hz, 1H), 5.50 (d, J=16.5 Hz, 1H), 4.91-4.90 (m, 1H), 3.75-3.73 (m, 1H), 3.29 (dd, J=3.5, 12.2 Hz, 1H), 2.96-2.83 (m, 3H), 1.77-1.57 (m, 4H), 1.43 (s, 9H).  
      MS (ESI+) 702 (M + +1, 100%).  
     Reference Example 162  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.11 (brs, 1H), 7.88-7.72 (m, 2H), 7.37-7.34 (m, 1H), 7.21-7.10 (m, 2H), 7.10-7.04 (m, 1H), 6.81-6.78 (m, 1H), 5.56 (d, J=16.5 Hz, 1H), 5.49 (d, J=16.5 Hz, 1H), 4.92 (brd, J=6.6 Hz, 1H), 3.77 (brs, 1H), 3.30 (dd, J=12.1 and 3.4, 1H), 2.95-2.84 (m, 3H), 1.93-1.70 (m, 3H), 1.59 (s, 9H), 1.43 (s, 9H).  
      MS (ESI+) (M + +1, 100%).  
     Reference Example 163  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.12 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 7.36 (dd, J=7.9 and 1.3 Hz, 1H), 7.28-7.26 (m, 1H), 7.21-7.14 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 5.58 (d, J=16.5 Hz, 1H), 5.51 (d, J=16.5 Hz, 1H), 4.92 (d, J=7.9 Hz, 1H), 3.83 (s, 3H), 3.78 (brs, 1H), 3.30 (dd, J=12.1 and 3.4 Hz, 1H), 2.92-2.84 (m, 3H), 1.76-1.68 (m, 3H), 1.58 (s, 9H), 1.54-1.48 (m, 1H), 1.43 (s, 9H).  
      MS (ESI+) 766 (M + +1, 100%).  
     Reference Example 164  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.08 (s, 1H), 7.48 (d, J=8.4 Hz, 2H), 7.37-7.34 (m, 1H), 7.27-7.13 (m, 4H), 6.82-6.79 (m, 1H), 5.58 (d, J=16.2 Hz, 1H), 5.50 (d, J=16.2 Hz, 1H), 4.93-4.91 (m, 1H), 4.13 (dd, J=7.1, 14.3 Hz, 2H), 3.78-3.75 (m, 1H), 3.57 (s, 2H), 3.29 (dd, J=3.3, 11.9 Hz, 1H), 2.92-2.86 (m, 3H), 1.74-1.58 (m, 4H), 1.43 (s, 9H), 1.24 (d, J=7.1 Hz, 3H).  
      MS (ESI+) 722 (M + +1, 100%).  
     Reference Example 165  
      MS (ESI+) 742 (M + +1, 100%).  
     Reference Example 166  
      MS (ESI+) 742 (M + +1, 100%).  
     Reference Example 167  
      MS (ESI+) 772 (M + +1, 100%).  
     Reference Example 168  
      MS (ESI+) 754 (M + +1, 100%).  
     Reference Example 169  
     tert-Butyl((3R)-1-{1-(2-chloro-5-fluorobenzyl)-4-iodo-5-[(pyridin-4-ylamino)carbonyl]-1H-imidazol-2-yl}piperidin-3-yl)carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (250 mg) was synthesized by the same process as in Reference Example 152. MS (ESI+) 655 (M + +1, 100%).  
     Reference Example 170  
     Methyl 4-({[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}amino)-1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (421 mg) was synthesized by the same process as in Reference Example 152.  
       1 H NMR (400 MHz, CDCl 3 ) δ 9.74 (s, 1H), 8.16 (s, 1H), 7.35 (dd, J=7.9 and 1.3 Hz, 1H), 7.22 (d, J=8.6 Hz, 2H), 7.19-7.11 (m, 2H), 6.86 (d, J=8.6 Hz, 2H), 6.69 (d, J=7.9 Hz, 1H), 5.53 (d, J=16.5 Hz, 1H), 5.46 (d, J=16.5 Hz, 1H), 5.24 (s, 2H), 4.88 (d, J=8.0 Hz, 1H), 3.99 (s, 3H), 3.79 (s, 3H), 3.74 (brs, 1H), 3.23 (dd, J=12.0 and 3.3 Hz, 1H), 2.89-2.81 (m, 3H), 1.73-1.53 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 804 (M + +1, 100%).  
     Reference Example 171  
     Methyl 3-({[2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazol-5-yl]carbonyl}amino)thiophene-2-carboxylate  
     
       
         
         
             
             
         
       
     
      The title compound (770 mg) was synthesized by the same process as in Reference Example 152.  
       1 H NMR (300 MHz, CDCl 3 ) δ 10.61 (brs, 1H), 8.01 (d, J=5.5 Hz, 1H), 7.44 (d, J=5.5 Hz, 1H), 7.36-7.33 (m, 1H). 7.20-7.12 (m, 2H), 6.77-6.73 (m, 1H), 5.50 (d, J=16.1 Hz, 1H), 5.43 (d, J=16.1 Hz, 1H), 4.92-4.90 (m, 1H), 3.90 (s, 3H), 3.76 (brs, 1H), 3.28 (dd, J=3.3, 12.3 Hz, 1H), 2.90-2.79 (m, 3H), 1.71-1.52 (m, 4H), 1.42 (s, 9H).  
      MS (ESI+) 700 (M + +1, 100%).  
     Reference Example 172  
     tert-Butyl [(3R)-1-[1-(2-chloro-5-fluorobenzyl)-4-iodo-5-{[(2-oxo-2,5-dihydrofuran-3-yl)amino]carbonyl}-1H-imidazo-2-yl]piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      N,N-dimethylformamide (three drops) and oxalyl chloride (0.15 mL) were added to a solution of 2-[(3R)-3-(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chloro-5-fluorobenzyl)-4-iodo-1H-imidazole-5-carboxylic acid (0.52 g) in dichloromethane (20 mL) at 0° C. After the resulting mixture was stirred at 25° C. for 4 hours, the solvent was distilled off by concentration under reduced pressure. Toluene (10 mL), diisopropylethylamine (0.3 mL) and 3-aminofuran-2(5H)-one (0.3 mL) were added to the residue and the resulting mixture was stirred at 120° C. for 8 hours. After the reaction solution was allowed to cool, a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel chromatography (hexane/ethyl acetate=5/1→1/1) to obtain the title compound.  
     Reference Example 173  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazole-5-carboxylic acid  
     
       
         
         
             
             
         
       
     
      A solution consisting of ethyl 2-[(3R)-3-(tert-butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chlorobenzyl)-4-iodo-1H-imidazole-5-carboxylate (7.0 g), 1N sodium hydroxide (20 mL) and ethanol (50 mL) was stirred at 80° C. for 1 hour. After the reaction mixture was concentrated under reduced pressure, a saturated aqueous ammonium chloride solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (6.5 g) as a light-yellow amorphous substance.  
      MS (ESI+) 561 (M + +1, 100%).  
     Reference Example 174  
     2-[(3R)-3-(tert-Butoxycarbonyl)amino]piperidin-1-yl}-1-(2-chloro-5-fluorobenzyl)-4-iodo-1H-imidazole-5-carboxylic acid  
     
       
         
         
             
             
         
       
     
      The title compound (30.3 g) was synthesized by the same process as in Reference Example 173.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.33 (m, 1H), 6.90 (m, 1H), 6.32 (d, J=9.0 Hz, 1H), 5.45-4.34 (m, 2H), 4.84 (m, 1H), 3.73-3.66 (m, 1H), 3.33-3.31 (m, 1H), 2.912.77 (m, 4H), 1.78-1.57 (m, 3H), 1.40 (s, 9H).  
      MS (ESI+) 579 (M + +1, 100%).  
     Reference Example 175  
     2-Methoxy-3-nitrobenzoic acid  
     
       
         
         
             
             
         
       
     
      A 3N aqueous sodium hydroxide solution (155 mL) was added to a solution of methyl 2-methoxy-3-nitrobenzoate (9.83 g) in a mixture of tetrahydrofuran and methanol (1:1, 400 mL) and stirred for 48 hours. The organic solvent was removed under reduced pressure and water (400 mL) was added to the residue to obtain a solution. This solution was acidified (pH=1) with 36% hydrochloric acid and extracted with ethyl acetate (3×200 mL). The combined organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (8.01 g).  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.29 (dd, J=7.9 and 1.7 Hz, 1H), 8.04 (dd, J=7.9 and 1.7 Hz, 1H), 7.38 (dd, J=7.9 and 7.9 Hz, 1H), 4.09 (s, 3H).  
      MS (ESI+) 198 (M + +1, 18%), 180 (100%).  
     Reference Example 176  
     Ethyl 2-methoxy-3-nitrobenzoate  
     
       
         
         
             
             
         
       
     
      A reactor containing a solution (500 mL) of 2-methoxy-3-nitrobenzoic acid (8.01 g) in ethanol was cooled in an ice-water bath and thionyl chloride (6.10 g) was added dropwise to the solution. After completion of the dropwise addition, the reaction solution was stirred for 8 hours with heating under reflux. The reaction solution was cooled and then concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (500 mL). The resulting solution was washed with a saturated aqueous sodium hydrogencarbonate solution (2×100 mL), dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (7.75 g) as a yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (dd, J=7.9 and 1.7 Hz, 1H), 7.91 (dd, J=7.9 and 1.7 Hz, 1H), 7.28 (dd, J=7.9 and 7.9 Hz, 1H), 4.43 (q, J=7.1 Hz, 2H), 4.01 (s, 3H), 1.42 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 226 (M + +1, 14%), 180 (100%).  
     Reference Example 177  
     Ethyl 3-amino-2-methoxybenzoate  
     
       
         
         
             
             
         
       
     
      To a solution of ethyl 2-methoxy-3-nitrobenzoate (7.75 g) in a mixture of tetrahydrofuran and methanol (1:1, 400 mL) was added 10% palladium-active carbon carrier (containing 50% water, 1.4 g), and the resulting mixture was stirred for 4 hours under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=6/1 to 3/1) to obtain the title compound (6.69 g) as a light-yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.19 (dd, J=7.9 and 1.7 Hz, 1H), 6.95 (dd, J=7.9 and 7.9 Hz, 1H), 6.90 (dd, J=7.9 and 1.7 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 3.94 (brs, 2H), 3.85 (s, 3H), 1.40 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 196 (M + +1, 7%), 150 (100%).  
     Reference Example 178  
     Ethyl 3-amino-2,6-difluorobenzoate  
     
       
         
         
             
             
         
       
     
      Tin chloride dihydrate (SnCl 2 .2H 2 O) (5.32 g) was added to a solution (50 mL) of ethyl 2,6-difluoro-3-nitrobenzoate (1.0 g) in ethanol, and the mixture was stirred for 2 hours with heating under reflux. After the reaction solution was cooled, the solvent was removed to obtain a yellow oil. This residue was dissolved in ethyl acetate (100 mL) and the resulting solution was made basic with a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate (4×50 ml). The combined organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=4/1) to obtain the title compound (819.7 mg) as a light-yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 6.85-6.74 (m, 2H), 4.42 (q, J=7.1 Hz, 2H), 3.68 (brs, 2H), 1.39 (t, J=7.1 Hz, 3H).  
      MS (ESI+) 202 (M + +1, 100%).  
     Reference Example 179  
     Methyl 4-amino-1-(4-methoxybenzyl)-1H-pyrazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      To a solution of methyl 1-(4-methoxybenzyl)-4-nitro-1H-pyrazole-5-carboxylate (6.54 g) in a mixture of tetrahydrofuran and methanol (1:3, 400 mL) was added 10% palladium-active carbon carrier (containing 50% water, 2.31 g), and the resulting mixture was stirred for 4 hours under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the title compound (5.11 g) as a light-yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.19 (d, J=8.6 Hz, 2H), 6.87 (d, J=8.6 Hz, 2H), 6.85 (s, 1H), 5.18 (s, 2H), 4.05 (brs, 2H), 3.93 (s, 3H), 3.80 (s, 3H).  
      MS (ESI+) 262 (M + +1, 100%).  
     Reference Example 180  
     tert-Butyl 2-fluoro-5-nitrobenzoate  
     
       
         
         
             
             
         
       
     
      N,N-dimethylaminopyridine (801 mg) and di-tert-butyl dicarbonate (9.54 g) were added to a suspension of 2-fluoro-5-nitrobenzoic acid (4.04 g) in tetrahydrofuran (60 mL) and stirred for 11 hours. Then, tert-butanol (60 mL) was added thereto and stirred for 24 hours. The reaction solution was filtered and the filtrate was concentrated under reduced pressure. The residue was suspended in ethyl acetate (500 mL) and the suspension was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=20/1) to obtain the title compound (4.652 g) as a light-yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.77-8.75 (m, 1H), 8.39-8.35 (m, 1H), 7.31-7.27 (m, 1H), 1.53 (s, 9H).  
     Reference Example 181  
     tert-Butyl 5-amino-2-fluorobenzoate  
     
       
         
         
             
             
         
       
     
      To a solution of tert-butyl 2-fluoro-5-nitrobenzoate (500 mg) in tetrahydrofuran (50 mL) was added 10% palladium-active carbon carrier (containing 50% water, 58 mg), and the resulting mixture was stirred for 6 hours under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated under reduced pressure to obtain the title compound (447.2 mg) as a yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 7.14-7.11 (m, 1H), 6.92-6.88 (m, 1H), 6.78-6.74 (m, 1H), 3.62 (brs, 2H), 1.53 (s, 9H).  
      MS (ESI + ) 212 (M + +1, 67%), 156 (100%).  
     Reference Example 182  
     3-Methoxy-5-nitrobenzoic acid  
     
       
         
         
             
             
         
       
     
      A 4N aqueous sodium hydroxide solution (56.9 ml) was added to a solution of methyl 3-methoxy-5-nitrobenzoate (9.60 g) in a mixture of tetrahydrofuran and methanol (1:1, 400 mL) and stirred for 48 hours. The organic solvent was removed under reduced pressure and water (150 mL) was added to the residue to obtain a solution. This solution was acidified with 36% hydrochloric acid and extracted with ethyl acetate (4×100 mL). The combined organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (8.96 g).  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.54 (dd, J=2.5 and 1.3 Hz, 1H), 7.98 (dd, J=2.5 and 2.5 Hz, 1H), 7.94 (dd, J=2.5 and 1.3 Hz, 1H), 3.97 (s, 3H).  
      MS (ESI + ) 198 (M + +1, 100%).  
     Reference Example 183  
     tert-Butyl 3-methoxy-5-nitrobenzoate  
     
       
         
         
             
             
         
       
     
      N,N-dimethylaminopyridine (1.66 g) and di-tert-butyl dicarbonate (19.86 g) were added to a solution of 3-methoxy-5-nitrobenzoic acid (8.96 g) in tetrahydrofuran (200 mL) and stirred for 24 hours. Then, tert-butanol (200 mL) was added thereto and stirred for 24 hours. The reaction solution was concentrated under reduced pressure and the residue was suspended in ethyl acetate (500 mL), followed by filtration. The filtrate was concentrated under reduced pressure and the residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=50/1) to obtain the title compound (10.68 g) as a light-yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 8.38 (dd, J=2.5 and 1.3 Hz, 1H), 7.88 (dd, J=2.5 and 2.5 Hz, 1H), 7.84 (dd, J=2.5 and 1.3 Hz, 1H), 3.94 (s, 3H), 1.62 (s, 9H).  
      MS (ESI + ) 198 (M + -tBu, 100%).  
     Reference Example 184  
     tert-Butyl 3-amino-5-methoxybenzoate  
     
       
         
         
             
             
         
       
     
      To a solution of tert-butyl 3-methoxy-5-nitrobenzoate (10.68 g) in tetrahydrofuran (500 mL) was added 10% palladium-active carbon carrier (containing 50% water, 2.0 g), and the resulting mixture was stirred for 6 hours under a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (developing solvent: hexane/ethyl acetate=10/1 to 1/1) to obtain the title compound (9.7 g) as a yellow oil.  
       1 H NMR (400 MHz, CDCl 3 ) δ 6.94-6.92 (m, 2H), 6.38 (dd, J=2.5 and 2.5 Hz, 1H), 3.79 (s, 5H), 1.57 (s, 9H).  
      MS (ESI + ) 224 (M + +1, 100%).  
     Reference Example 185  
     tert-Butyl 2-{(3R)-3-[(tert-butoxycarbonyl)-amino]piperidin-1-yl}-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate  
     
       
         
         
             
             
         
       
     
      Ammonium formate (2.55 g) and 10% palladium-carbon (2.50 g) were added to a solution (100 mL) of tert-butyl 2-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-7-carboxylate (2.52 g) in methanol, and the resulting mixture was stirred with heating at 70° C. for 3 hours in a nitrogen stream. After completion of the reaction, the palladium-carbon was removed by filtration and the solvent was distilled off under reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, followed by extraction with ethyl acetate (200 mL). The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol=100/1 to 25/1) to obtain the title compound (1.63 g) as a light-yellow solid.  
       1 H NMR (300 MHz, CDCl 3 ) δ ppm 11.95 (bs, 1H), 8.24 (d, J=7.9 Hz, 1H), 7.92 (s, 1H), 7.91 (d, J=7.9 Hz, 1H), 5.00 (d, J=7.0 Hz), 3.88 (s, 3H), 3.75-3.65 (m, 5H), 1.92-1.52 (m, 4H), 1.65 (s, 9H), 1.40 (s, 9H).  
      MS (ESI+) 498 (M + +1, 100%).  
     Reference Example 186  
     2-{(3R)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-(2-chlorobenzyl)-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinoline-8-carboxylic acid  
     
       
         
         
             
             
         
       
     
      The title compound (5.0 mg) was synthesized by the same process as in Reference Example 120.  
      MS (ESI+) 552 (M + +1, 100%).  
     Reference Example 187  
     Methyl 1-(4-methoxybenzyl)-4-nitro-1H-pyrazole-5-carboxylate  
     
       
         
         
             
             
         
       
     
      4-Methoxybenzyl chloride (5.04 g) and potassium carbonate (4.45 g) were added to a solution (60 mL) of methyl 4-nitro-1H-pyrazole-5-carboxylate (5.00 g) in N,N-dimethylformamide, and the resulting mixture was stirred with heating at 60° C. for 12 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate/hexane=1/4 to 1/1) to obtain the title compound (6.54 g).  
      MS (ESI+) 292 (M + +1, 100%).  
     Reference Example 188  
     Methyl 7-{(3R)-3-[(tert-butoxycarbonyl)amino]-piperidin-1-yl}-6-(2-chlorobenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate  
     
       
         
         
             
             
         
       
     
      Trifluoroacetic acid (17 mL) and concentrated sulfuric acid (0.5 mL) were added to a solution of methyl 7-{(3R)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6-(2-chlorobenzyl)-2-(4-methoxybenzyl)-4-methyl-5-oxo-2,4,5,6-tetrahydroimidazo[4,5-d]pyrazolo[4,3-b]pyridine-3-carboxylate (139 mg) in anisole (1 mL), and the resulting mixture was allowed to stand at room temperature for 5 days. The solvent for reaction was distilled off under reduced pressure and the residue was diluted with tetrahydrofuran (50 mL) and then adjusted to pH 10 with a saturated aqueous sodium hydrogencarbonate solution. To the resulting mixed solution was added di-tert-butyl dicarbonate (88 mg), and the resulting mixture was stirred at room temperature for 5 hours. The tetrahydrofuran was removed under reduced pressure, followed by two runs of extraction with ethyl acetate (30 mL). The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: ethyl acetate/hexane=1/1 to 1/0) to obtain the title compound (94 mg).  
       1 H NMR (400 MHz, CD 3 OD) δ 7.45 (dd, J=7.9 and 1.3 Hz, 1H), 7.26 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 7.20 (ddd, J=7.9, 7.9 and 1.3 Hz, 1H), 6.73 (d, J=7.9 Hz, 1H), 5.71 (s, 2H), 3.97 (s, 3H), 3.85 (s, 3H), 3.64 (brs, 1H), 3.49-3.46 (m, 1H), 3.26-3.23 (m, 1H), 2.96-2.92 (m, 1H), 2.85-2.80 (m, 1H), 1.85-1.66 (m, 4H), 1.41 (s, 9H).  
      MS (ESI + ) 570 (M + +1, 100%).  
     Reference Example 189  
     tert-Butyl {(3R)-1-[3-(2-chlorobenzyl)-5-methyl-4,7-dioxo-4,5,7,9-tetrahydro-3H-furo[3,4-g]imidazo[4,5-c]quinolin-2-yl]piperidin-3-yl}carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (3.7 mg) was synthesized by the same process as in Reference Example 76.  
      MS (ESI+) 596 (M + +1, 100%).  
     Reference Example 190  
     tert-Butyl [(3R)-1-(1-(2-chlorobenzyl)-4-iodo-5-{[methyl(3-oxo-1,3-dihydro-2-benzofuran-5-yl)amino]-carbonyl}-1H-imidazol-2-yl)piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (25 mg) was synthesized by the same process as in Reference Example 130.  
      MS (ESI+) 724 (M + +1, 100%).  
     Reference Example 191  
     tert-Butyl [(3R)-1-(1-(2-chlorobenzyl)-4-iodo-5-{[(3-oxo-1,3-dihydro-2-benzofuran-5-yl)amino]carbonyl}-1H-imidazol-2-yl)piperidin-3-yl]carbamate  
     
       
         
         
             
             
         
       
     
      The title compound (64 mg) was synthesized by the same process as in Reference Example 152.  
      MS (ESI+) 710 (M + +1, 100%).  
     Test Examples  
      In Vitro DPP-IV Inhibitory Effect Measurement Test (1)  
      Bovine plasma containing DPP-IV enzyme was diluted with assay buffer (25 mM Tris-HCl, 140 mM NaCl, 10 mM KCl, pH=7.9) and 50 μL of the dilution was added to a micro assay plate. After 1 μL of a solution of each compound was added, mixing was conducted, followed by incubation at room temperature. A substrate (Glycyl-L-Proline 4-Methyl-Coumaryl-7-Amide, Peptide Laboratories Co., Ltd.) was diluted to 0.2 mM with the assay buffer, and 50 μL of this solution was added and then stirred, followed by incubation at room temperature. Thereafter, the reaction was terminated by the addition of 100 μL of a 25% aqueous acetic acid solution. The intensity of fluorescence at an excitation wavelength of 360 nm and a measuring wavelength of 460 nm was measured by the use of a fluorescent plate reader. The difference in intensity of fluorescence between a background well in which the reaction had been terminated by previously adding a 25% aqueous acetic acid solution before the addition of the substrate solution and a control well to which no compound had been added was taken as 100%. The intensity of fluorescence of a well containing the compound was interpolated and the residual enzyme activity in the case of the addition of the compound was calculated as a relative value. A compound concentration for 50% inhibition of the enzyme activity was calculated as an IC 50  value from relative residual enzyme activity values obtained by adding each compound to a plurality of concentrations.  
      Compounds of Examples were used in this test. The results obtained are shown in Table 1.  
                           TABLE 1                                   Compound   IC 50  (nM)                                                    Compound of Example 2   11.0           Compound of Example 4   68.0           Compound of Example 7   1.4           Compound of Example 11   44.0           Compound of Example 13   5.0           Compound of Example 30   203.0           Compound of Example 38   112.0                      
 
 In Vitro DPP-IV Inhibitory Effect Measurement Test (2) 
 
      Human serum containing DPP-IV enzyme was used in an experiment after being diluted with assay buffer (25 mM Tris-HCl, 140 mM NaCl, 10 mM KCl, pH 7.9) (finally, diluted 10-fold). Each of solutions of each test compound having various concentrations was added to the diluted serum and the resulting mixture was incubated at room temperature. Then, a substrate (Glycyl-L-Proline 4-Methyl-Coumaryl-7-Amide, Peptide Laboratories Co., Ltd.) was added thereto to a final concentration of 100 μM and the reaction was carried out at room temperature. Acetic acid was added to the reaction mixture to a final concentration of 12.5% to terminate the reaction, and the intensity of fluorescence at an excitation wavelength of 360 nm and a measuring wavelength of 460 nm was measured by the use of a fluorescent plate reader. A compound concentration for 50% inhibition was calculated as an IC 50  value from enzyme inhibitory activity values obtained by adding each test compound to a plurality of concentrations.  
      Compounds of Examples were used in this test. The results obtained are shown in Table 2.  
                           TABLE 2                                   Compound   IC 50  (nM)                                                    Compound of Example 46   418.0           Compound of Example 47   51.0           Compound of Example 48   45.0           Compound of Example 49   271.0           Compound of Example 50   21.0           Compound of Example 51   12.0           Compound of Example 52   72.0           Compound of Example 53   16.0           Compound of Example 54   3.6           Compound of Example 55   6.6           Compound of Example 56   4.6           Compound of Example 57   103.0           Compound of Example 58   2.4           Compound of Example 59   47.0           Compound of Example 60   38.0           Compound of Example 61   11.0           Compound of Example 65   3.5           Compound of Example 66   5.4           Compound of Example 67   5.8           Compound of Example 68   130.0           Compound of Example 71   2.3           Compound of Example 72   4.0           Compound of Example 73   60.0           Compound of Example 74   12.0           Compound of Example 75   12.0           Compound of Example 76   13.0           Compound of Example 77   13.0           Compound of Example 78   17.0           Compound of Example 79   17.0           Compound of Example 80   24.0           Compound of Example 81   94.0           Compound of Example 87   6.6           Compound of Example 88   0.9           Compound of Example 89   14.0           Compound of Example 90   11.0           Compound of Example 92   7.0           Compound of Example 94   42.0           Compound of Example 95   98.0           Compound of Example 97   14.0           Compound of Example 98   1.2           Compound of Example 99   1.5           Compound of Example 100   0.5           Compound of Example 102   12.0                      
 
     INDUSTRIAL APPLICABILITY  
      The present invention makes it possible to provide compounds having DPP-IV inhibitory activity and improved in safety, non-toxicity and the like.  
      The present inventive compounds are useful for the suppression of postprandial hyperglycemia in a prediabetic, the treatment of non-insulin-dependent diabetes mellitus, the treatment of autoimmune diseases such as arthritis and articular rheumatism, the treatment of intestinal mucosa diseases, growth acceleration, the inhibition of rejection of a transplantate, the treatment of corpulence, the treatment of eating disorder, the treatment of HIV infection, the suppression of cancer metastasis, the treatment of prostatomegaly, the treatment of periodontitis, and the treatment of osteoporosis.