Patent Publication Number: US-2023142119-A1

Title: Tetracyclic compound

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation of U.S. application Ser. No. 15/221,926, filed Jul. 28, 2016, which is a Continuation of U.S. application Ser. No. 14/619,242, filed Feb. 11, 2015, which is a Divisional of U.S. application Ser. No. 13/377,300, which is the U.S. National Stage application of PCT/JP2010/059785, filed Jun. 9, 2010, which claims priority from Japanese application JP 2009-139691, filed Jun. 10, 2009. 
    
    
     TECHNICAL FIELD 
     The present invention relates to tetracyclic compounds, salts or solvates thereof. More specifically, the present invention relates to the tetracyclic compounds and provides a medicament, pharmaceutical compositions comprising the compounds, ALK inhibitors, and pharmaceuticals for the prophylaxis or treatment of the diseases including cancer, cancer metastasis, depression or cognitive function disorder comprising the compounds. Furthermore, the present invention relates to a method for the treatment of the diseases comprising administering to the patient who is in need of the treatment of the disease the compounds described herein, salts or solvates thereof in an effective amount for the treatment of the diseases, and use of the tetracyclic compounds for the preparation of the pharmaceutical composition. 
     BACKGROUND ART 
     Anaplastic Lymphoma Kinase (ALK) is one of the receptor tyrosine kinases belonging to insulin receptor family (Non-Patent Document Nos. 1 and 2). It was reported that, due to gene alteration of ALK (translocation, point mutation and gene amplification), an abnormal activation of ALK is eventually involved in oncogenesis. 
     For example, in lung cancer, ALK forms EML4-ALK due to chromosomal translocation, leading to constitutive activation of tyrosine kinase, and it acquires a tumorigenic activity (Non-Patent Document 1). In addition, the ALK translocation were reported in systemic anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs) (Non-Patent Document Nos. 3 and 4), and esophageal cancer (Non-Patent Document 5). It was also found that active point mutation (approximately 10%) or gene amplification of ALK is involved in oncogenesis of neuroblastoma (Non-Patent Document Nos. 6 and 7). 
     On the other hand, it was also reported in tumors activated by pleiotrophin (PTN) or midkine (MK) (Non-Patent Document Nos. 8 and 9), both a ligand for ALK. 
     Further, from the study using ALK knock-out mouse, it was suggested that an inhibitor for ALK is useful as an anti-depression agent or as a preventive or therapeutic agent for cognitive function disorders (Non-Patent Document 10 and Patent Document 1). 
     Therefore, a compound having an inhibitory activity on ALK will be very useful for the prevention and treatment of cancer, depression and cognitive function disorders, etc. 
     Meanwhile, as an ALK inhibiting material, there are some compounds among multi-kinase inhibitors which have an inhibitory activity on ALK as one of their activities. For example, as an inhibitor for c-MET (mesenchymal-epithelial transition factor) and ALK, PF02341066 having a 2-aminopyridine structure was reported (Patent Document 2, Non-Patent Document Nos. 11 and 12). As an inhibitor for FAK, ZAP70, IGF-1R and ALK, etc., NVP-TAE684 having a 2,4-diaminopyrimidine structure was reported (Patent Document 3 and Non-Patent Document 13). In addition, 2,4-diaminopyrimidines and 2,4-diaminoquinazolines (Patent Document 4), pyridopyrazines (Patent Document 5), pyrazolo [3,4-C] isoquinolines (Patent Document 6), thiazoles (Patent Document 7), tricyclic compounds (Patent Document 8), and indazoles (Patent Document 9) and the like have been reported. 
     However, the tetracyclic compounds of the present invention are not disclosed in any of the documents described above. 
     As a tetracyclic compound exhibiting an anti-tumor activity, tetracyclic compounds comprising carbazole structure like ellipticine are known. 
     However, their action mechanism is based on interaction with DNA to exhibit cell toxicity (Non-Patent Document 15), and there is no description at all regarding the activity of inhibiting ALK by the tetracyclic compounds. 
     DOCUMENT LIST 
     
         
         [Patent Document 1] WO 2007/023310 A2 
         [Patent Document 2] WO 2006/021884 A2 
         [Patent Document 3] WO 2004/080980 A1 
         [Patent Document 4] WO 2009/008371 A1 
         [Patent Document 5] WO 2007/130468 A2 
         [Patent Document 6] WO 2005/009389 A2 
         [Patent Document 7] WO 2005/097765 A1 
         [Patent Document 8] WO 2008/021369 A2 
         [Patent Document 9] WO 2009/013126 A1 
         [Non-Patent Document 1] Proc Natl Acad Sci USA, Vol. 101, pages 13306-13311, 2004 
         [Non-Patent Document 2] Nature, Vol. 448, pages 561-566, 2007 
         [Non-Patent Document 3] Blood, Vol. 72, pages 234-240, 1988 
         [Non-Patent Document 4] Cancer Res, Vol. 59, pages 2776-2780, 1999 
         [Non-Patent Document 5] World J Gastroenterol, Vol. 12, pages 7104-7112, 2006 
         [Non-Patent Document 6] Nature, Vol. 455, pages 930-935, 2008 
         [Non-Patent Document 7] Nature, Vol. 455, pages 971-974, 2008 
         [Non-Patent Document 8] J Biol Chem, Vol. 276, pages 16772-16779, 2001 
         [Non-Patent Document 9] J Biol Chem, Vol. 277, pages 35990-35999, 2002 
         [Non-Patent Document 10] Neuropsychopharmacology, Vol. 33, pages 685-700, 2008 
         [Non-Patent Document 11] Proc Am Assoc Cancer Res (AACR) 2006, 47: Abst LB-271 
         [Non-Patent Document 12] Proc Am Assoc Cancer Res (AACR) 2006, 47: Abst LB-273 
         [Non-Patent Document 13] Proc Natl Acad Sci USA Vol. 104, pages 270-275, 2007 
         [Non-Patent Document 14] Current Organic Chemistry, Vol. 5, Issue No. 5, pages 507-518, 2001 
         [Non-Patent Document 15] Current Medicinal Chemistry: Anti-Cancer Agents, Vol. 4, Issue No. 2, pages 149-172, 2004 
       
    
     SUMMARY OF THE INVENTION 
     Problems to be Solved by the Invention 
     The present invention is to provide ALK-inhibiting compounds having a novel structure. In addition, object of the present invention is to provide a pharmaceuticals for the prophylaxis or treatment comprising the ALK-inhibiting compounds that is effective for prophylaxising or treating a disease accompanied by abnormality in ALK, for example, cancer, cancer metastasis, depression and cognitive function disorder. 
     Means for Solving the Problems 
     As a result of extensive studies by the inventors of the present invention, it was found that the tetracyclic compounds that are represented by the following Formula (1) with a structure clearly different from any other existing pharmaceutical compounds have an excellent ALK-inhibiting activity, are useful for the treatment and prophylaxis of the diseases including cancer, cancer metastasis, depression and cognitive function disorder, and have a remarkable efficacy against said diseases. Accordingly, the present invention was completed. 
     Thus, according to one aspect of the present invention, the tetracyclic compounds, a medicament and a pharmaceutical composition comprising the compounds, etc. shown below are provided. 
     [1] A compound or salt or solvate thereof represented by Formula (I): 
     
       
         
         
             
             
         
       
     
     [wherein, 
     A 1 , A 2 , A 3 , A 4 , A 7 , A 8 , A 9  and A 10  all represent C, or any one of A 2 , A 3 , A 4 , A 7 , A 8  and A 9  represents N (with the proviso that, when it represents N, no substituent group exists therefor) and the remainings represent C; 
     A 5  is selected from NR 5 , O and S; 
     R 1  and R 10  each independently represent [1] a hydrogen atom, [2] a cyano group, [3] a halogen atom or [4] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s); 
     R 2  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group, 
     (3) a C 2-8  alkenyl group, 
     (4) a C 2-8  alkynyl group, 
     (5) a cyano group, 
     (6) a halogen atom, 
     (7) a (C 1-8  alkyl) m2 -amino group which may be substituted by C 1-8  alkylsulfonyl group(s),
         m2: 0˜2, and       

     (8) a nitro group; 
     R 3  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by [1] halogen atom(s), [2]hydroxy group(s) or [3] C 1-8  alkoxy group(s), 
     (3) a C 6-10  aryl group, 
     (4) a cyano group, 
     (5) a C 1-8  alkanoyl group which may be substituted by C 6-10  aryl group(s), 
     (6) a (C 1-8  alkyl) m3a -aminocarbonyl group which may be substituted by one or more R 3A , 
     R 3A : [1] a C 6-10  aryl group, [2] a C 1-8  alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C 6-10  aryl sulfonyl group,
         m3a: 0˜2,       

     (7) a hydroxycarbonyl group, 
     (8) a C 1-8  alkoxycarbonyl group which may be substituted by [1] hydroxy group(s) or [2] C 1-8  alkoxy group(s), 
     (9) a halogen atom, 
     (10) a (C 1-8  alkyl) m3b -amino group which may be substituted by C 6-10  aryl group(s),
         m3b: 0˜2,       

     (11) a C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group which may be substituted by [1]C 6-10  aryl group(s) or [2] C 6-10  aryloxy group(s), 
     (12) a C 6-10  arylcarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkyl group(s) which may be substituted by halogen atom(s), 
     (13) a (C 1-8  alkyl) m3c -aminocarbonyl (C 0-8  alkyl) amino group which may be substituted by C 6-10  aryl group(s),
         m3c: 0˜2,       

     (14) a nitro group, 
     (15) a hydroxy group, 
     (16) a C 1-8  alkoxy group which may be substituted by one or more R 3B , 
     R 3B : [1] a hydroxy group, [2] a C 1-8  alkoxy group, [3] a C 6-10  aryl (C 0-8  alkyl) aminocarbonyl group, [4] a (C 1-8  alkyl) m3d -amino group, or [5] a halogen atom,
         m3d: 0˜2,       

     (17) a 4- to 10-membered heterocycloalkyloxy group, 
     (18) a 5- to 14-membered heteroaryloxy group, 
     (19) a (C 1-8  alkyl) m3e -aminocarbonyloxy group which may be substituted by C 6-10  aryl group(s)
         m3e: 0˜2,       

     (20) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, 
     (21) a C 1-8  alkylsulfonyloxy group which may be substituted by halogen atom(s), 
     (22) a C 1-8  alkylthio group, 
     (23) a C 1-8  alkylsulfonyl group which may be substituted by C 6-10  aryl group(s), 
     (24) a 5- to 14-membered heteroaryl group which may be substituted by C 1-8  alkyl group(s) which may be substituted by C 1-8  alkoxy group(s), 
     (25) a C 1-8  alkoxycarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkoxy group(s), 
     (26) a C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkyl group(s) which may be substituted by halogen atom(s), 
     (27) a C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group which may be substituted by one or more R 3C , 
     R 3C : [1] a C 1-8  alkyl group which may be substituted by halogen atom(s), or [2] a C 1-8  alkoxy group, 
     (28) a C 3-8  cycloalkyl (C 0-8  alkyl) aminocarbonyloxy group, and 
     (29) a C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkyl group and [2] a C 1-8  alkoxy group; 
     R 4  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by halogen atom(s), 
     (3) a C 2-8  alkenyl group, 
     (4) a C 2-8  alkynyl group, 
     (5) a C 3-8  cycloalkyl group, 
     (6) a cyano group, 
     (7) an aminocarbonyl group, 
     (8) a (C 1-8  alkyl) m4a -aminocarbonyl group,
         m4a: 1˜2,       

     (9) a hydroxycarbonyl group, 
     (10) a C 1-8  alkoxycarbonyl group, 
     (11) a halogen atom, 
     (12) a (C 1-8  alkyl) m4b -amino group,
         m4b: 0˜2,       

     (13) a hydroxy group, and 
     (14) a C 1-8  alkoxy group which may be substituted by hydroxy group(s); 
     R 5  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more RA, 
     R 5A : [1] a hydroxycarbonyl group, [2] a C 1-8  alkoxycarbonyl group, [3] a hydroxy group, [4] a C 1-8  alkoxy group, [5] a (C 1-8  alkyl) m5 -amino group, [6] a C 6-10  aryl group, or [7] a C 1-8  alkylthio group,
         m5: 0˜2,       

     (3) a C 2-8  alkenyl group, 
     (4) a C 2-8  alkynyl group, 
     (5) a C 3-8  cycloalkyl group, and 
     (6) a C 1-8  alkylsulfonyl group; 
     R 6  and R 6′  are each independently selected from the group consisting of: 
     (1) a C 1-8  alkyl group which may be substituted by halogen atom(s), 
     (2) a C 2-8  alkenyl group, and 
     (3) a C 2-8  alkynyl group; or 
     R 6  and R 6′  are taken together with the carbon atoms to which they are bound to form: 
     (4) a C 3-8  cycloalkyl group, or 
     (5) a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8  alkyl C 6-10  aryl sulfonyl group(s) which may be substituted by C 1-8  alkyl group(s); 
     R 7  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a halogen atom, 
     (3) a C 1-8  alkoxy group which may be substituted by one or more R 7A , 
     R 7A : [1] a (C 1-8  alkyl)m7a-amino group, [2] a hydroxy, [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8  alkyl group(s), 
     m7a: 0˜2, 
     (4) a C 1-8  alkylsulfonyl group, 
     (5) a nitro group, and 
     (6) a hydroxyl group; 
     R 8  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more R 8A , 
     R 8A : [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8A1 , [2] a (C 1-8  alkyl) m8a -amino group which may be substituted by a halogen atom, and [3] a hydroxy group,
         m8a: 0˜2,       

     R 8A1 : [1] a C 1-8  alkyl group, [2] a C 1-8  alkylsulfonyl group, [3] a (C 1-8  alkyl) m8b -aminosulfonyl group, [4] an oxo group, [5] a C 1-8  alkoxycarbonyl, or [6] a C 1-8  alkoxycarbonyl (C 0-8  alkyl) aminosulfonyl,
         m8b: 0˜2,       

     (3) a C 2-8  alkenyl group, 
     (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B , 
     R 8B : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by one or more R 8B1 ,
 
&lt;2&gt; a C 2-8  alkenyl group,
 
&lt;3&gt; a C 2-8  alkynyl group,
 
&lt;4&gt; a C 3-8  cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C 1-8  alkyl group(s),
 
&lt;5&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B2 ,
 
&lt;6&gt; a C 1-8  alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkoxy group and [2] a C 3-8  cycloalkyl group,
 
&lt;7&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;8&gt; a C 1-8  alkylsulfonyl group,
 
&lt;9&gt; a 5- to 14-membered heteroarylsulfonyl group,
 
&lt;10&gt; an oxo group,
 
&lt;11&gt; a cyano group,
 
&lt;12&gt; a C 1-8  alkanoyl group which may be substituted by one or more R 8B3 ,
 
&lt;13&gt; a C 3-8  cycloalkylcarbonyl group,
 
&lt;14&gt; a (C 1-8  alkyl) m8c -aminosulfonyl group,
 
&lt;15&gt; a C 1-8  alkylsulfonyl (C 0-8  alkyl) amino group,
 
&lt;16&gt; a (C 1-8  alkyl) m8a -amino group which may be substituted by one or more R 8B4 ,
 
&lt;17&gt; a hydroxy group,
 
&lt;18&gt; a (C 1-8  alkyl) m8e -aminocarbonyl group, or
 
&lt;19&gt; a C 1-8  alkoxycarbonyl (C 0-8  alkyl) amino group
         m8c: 0˜2   m8d: 0˜2   m8e: 0˜2       

     R 8B1 : [1] a C 3-8  cycloalkyl group, [2] a hydroxy group, or [3] a C 1-8  alkoxy group(s), 
     R 8B2 : [1] a halogen atom, [2] a C 1-8  alkyl group, [3] an oxo group, [4] a hydroxy group, or [5] a deuterium atom, 
     R 8B3 : a (C 1-8  alkyl) m8f -amino group,
         m8f: 0˜2,       

     R 8B4 : [1] a C 3-8  cycloalkyl group, or [2] a hydroxy group, 
     (5) a 5- to 14-membered heteroaryl group which may be substituted by a C 1-8  alkyl group, 
     (6) a (C 1-8  alkyl) m8g -aminocarbonyl group which may be substituted by one or more R 8C ,
         m8g: 0˜2,       

     R 8C : [1] a hydroxy group, [2] a (C 1-8  alkyl) m8h -amino group which may be substituted by substituent(s) selected from the group consisting of &lt;1&gt; a (C 1-8  alkyl) m8i -aminosulfonyl group, &lt;2&gt; a C 1-8  alkylsulfonyl group, &lt;3&gt; a C 1-8  alkoxycarbonyl group and &lt;4&gt; a C 1-8  alkoxycarbonyl(C 0-8  alkyl) aminosulfonyl group, [3] a C 1-8  alkylsulfonyl group, or [4] a C 1-8  alkoxy group which may be substituted by a hydroxy group,
         m8h: 0˜2,   m8i: 0˜2,       

     (7) a 4- to 10-membered heterocycloalkyl (C 0-8  alkyl) aminocarbonyl group which may be substituted by oxo group(s), 
     (8) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R 8D , 
     R 8D : [1] a C 1-8  alkyl group which may be substituted by one or more R 8D1 , [2] a hydroxy group, [3] a C 1-8  alkylsulfonyl group, or [4] a C 1-8  alkoxycarbonyl group, 
     R 8D1 : [1] a hydroxy group, or [2] a C 1-8  alkoxy group, 
     (9) a hydroxycarbonyl group, 
     (10) a C 0-8  alkoxy (C 0-8  alkyl) aminocarbonyl group which may be substituted by hydroxy group(s), 
     (11) a halogen atom, 
     (12) a (C 1-8  alkyl) m8j -amino group which may be substituted by one or more R 8H ,
         m8j: 0˜2,       

     R 8H : [1] a hydroxy group, or [2] a 4- to 10-membered heterocycloalkyl group, 
     (13) a hydroxyl group, 
     (14) a C 1-8  alkoxy group which may be substituted by one or more R 8E , 
     R 8E : 
     &lt;1&gt; a hydroxy group,
 
&lt;2&gt; halogen atom,
 
&lt;3&gt; a hydroxycarbonyl group,
 
&lt;4&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;5&gt; a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R 8E1 ,
 
&lt;6&gt; a (C 1-8  alkyl) m8k1 -amino group which may be substituted by one or more R 8E2 ,
         m8k1: 0˜2,
 
&lt;7&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8E3 ,
 
&lt;8&gt; a 5- to 14-membered heteroaryl group,
 
&lt;9&gt; a (C 1-8  alkyl) m8k2 -aminocarbonyl group which may be substituted by one or more R 8E6 ,
   m8k2: 0˜2,
 
&lt;10&gt; a C 1-8  alkoxy group which may be substituted by one or more R 8E7 ,
 
&lt;11&gt; a C 1-8  alkylthio group,
 
&lt;12&gt; a C 1-8  alkylsulfinyl group,
 
&lt;13&gt; a C 1-8  alkylsulfonyl group,
       

     R 8E1 : 
     &lt;1&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;2&gt; a C 1-8  alkanoyl group,
 
&lt;3&gt; a C 1-8  alkylsulfonyl group,
 
&lt;4&gt; a (C 1-8  alkyl) m8k3 -aminosulfonyl group,
         m8k3: 0˜2, or
 
&lt;5&gt; a 4- to 10-membered heterocycloalkyl group,
       

     R 8E2 : 
     &lt;1&gt; a hydroxy group,
 
&lt;2&gt; a C 1-8  alkoxycarbonyl group which may be substituted by halogen atom(s),
 
&lt;3&gt; a C 3-8  cycloalkyl group which may be substituted by C 1-8  alkyl group(s) which may be substituted by hydroxy group(s),
 
&lt;4&gt; a C 1-8  alkanoyl group which may be substituted by substituent(s) selected from the group consisting of [1] a (C 1-8  alkyl) m8k4 -amino group and [2] a halogen atom(s),
         m8k4: 0˜2,
 
&lt;5&gt; a (C 1-8  alkyl) m8k5 -aminocarbonyl group,
   m8k5: 0˜2,
 
&lt;6&gt; a C 1-8  alkylsulfonyl group,
 
&lt;7&gt; a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C 1-8  alkyl group(s),
 
&lt;8&gt; a (C 1-8  alkyl) m8k6 -aminosulfonyl group which may be substituted by C 1-8  alkoxycarbonyl group(s),
   m8k6: 0˜2, or       

     R 8E3 : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a hydroxy group and [2] a C 1-8  alkylcarbonyloxy group,
 
&lt;2&gt; a C 1-8  alkylcarbonyloxy group,
 
&lt;3&gt; a hydroxy group,
 
&lt;4&gt; a C 3-8  cycloalkyl group,
 
&lt;5&gt; a C 1-8  alkoxy group,
 
&lt;6&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;7&gt; a C 1-8  alkylsulfonyl group,
 
&lt;8&gt; a (C 1-8  alkyl) m8k8 -aminocarbonyl group
         m8k8: 0˜2,
 
&lt;9&gt; a C 1-8  alkanoyl group which may be substituted by hydroxy group(s),
 
&lt;10&gt; an oxo group, or
 
&lt;11&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkanoyl group, [2] a C 1-8  alkoxycarbonyl group and [3] a C 1-8  alkylsulfonyl group,
       

     R 8E6 : 
     &lt;1&gt; a C 2-8  alkenylcarbonyloxy group,
 
&lt;2&gt; a hydroxy group,
 
&lt;3&gt; a cyano group,
 
&lt;4&gt; a (C 1-8  alkyl) m8k9 -amino group which may be substituted by hydroxy group(s)
         m8k9: 0˜2,
 
&lt;5&gt; a C 1-8  alkoxy group which may be substituted by hydroxy group(s),
 
&lt;6&gt; a C 1-8  alkylcarbonyloxy group,
 
&lt;7&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8  alkyl group(s), or
 
&lt;8&gt; a 5- to 14-membered heteroaryl group,
       

     R 8E7 : 
     &lt;1&gt; a hydroxy group, or
 
&lt;2&gt; a C 1-8  alkoxy group which may be substituted by hydroxy group(s),
 
     (15) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R 8F , 
     R 8F : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by one or more R 8F1 ,
 
&lt;2&gt; a C 3-8  cycloalkyl group,
 
&lt;3&gt; a C 1-8  alkanoyl group which may be substituted by halogen atom(s),
 
&lt;4&gt; a C 1-8  alkylcarbonyloxy group,
 
&lt;5&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;6&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more
 
     R 8F2 , 
     &lt;7&gt; a C 1-8  alkyl sulfonyl group,
 
&lt;8&gt; a hydroxy group, or
 
[9] a C 6-10  aryl group,
 
     R 8F1 : [1] a hydroxy group, [2] a C 1-8  alkoxy group, or [3] a halogen atom, 
     R 8F2 : [1] a 4- to 10-membered heterocycloalkyl group, [2] a C 1-8  alkoxycarbonyl group, or [3] a C 1-8  alkylsulfonyl group, 
     (16) a 5- to 14-membered heteroaryloxy group, 
     (17) a 4- to 10-membered heterocycloalkylcarbonyloxy group, 
     (18) a (C 1-8  alkyl) m8l1 -aminosulfonyloxy group,
         m8l1: 0˜2,       

     (19) a C 1-8  alkyl thio group which may be substituted by [1] (C 1-8  alkyl) m8l2 -amino group(s), [2] hydroxy group(s) or [3] hydroxycarbonyl group(s),
         m8l2: 0˜2,       

     (20) a C 1-8  alkylsulfonyl group which may be substituted by one or more R 8G , 
     R 8G : [1] a hydroxycarbonyl group, [2] a hydroxy group, or [3] a (C 1-8  alkyl) m8l3 -amino group,
         m8l3: 0˜2,       

     (21) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group which may be substituted by C 1-8  alkyl group(s), 
     (22) a C 2-8  alkenyloxy group, and 
     (23) a C 1-8  alkylsulfonyloxy group which may be substituted by halogen atom(s); 
     R 9  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more R 9A , 
     R 9A : [1] a C 3-8  cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9A , [3] a hydroxy group, [4] a C 1-8  alkoxy group, or [5] a hydroxycarbonyl group, 
     R 9A1 : [1] a C 1-8  alkyl group, [2] a C 3-8  cycloalkyl group, or [3] a 4- to 10-membered heterocycloalkyl group, 
     (3) a C 2-8  alkenyl group which may be substituted by one or more R 9B , 
     R 9B : [1] a (C 1-8  alkyl) m9a -amino group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more group R 9B1 , 
     R 9B1 : [1] a C 3-8  cycloalkyl group, or [2] a 4- to 10-membered heterocycloalkyl group,
         m9a: 0˜2,       

     (4) a C 2-8  alkynyl group which may be substituted by one or more R 9C , 
     R 9C : [1] a C 1-8  alkoxy group, [2] a (C 1-8  alkyl) m9b -amino group which may be substituted by C 6-10  aryl group(s), [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9C1 , [4] a C 3-8  cycloalkyl group, [5] a hydroxy group, [6] a hydroxycarbonyl group, or [7] a C 1-8  alkyloxycarbonyl group,
         m9b: 0˜2,       

     R 9C1 : [1] a C 3-8  cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group, or [3] an oxo group, 
     (5) a C 3-8  cycloalkyl group, 
     (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9D , 
     R 9D : [1] a C 1-8  alkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), [2] a C 3-8  cycloalkyl group, [3] a 4- to 10-membered heterocycloalkyl group, or [4] a C 1-6  alkylsulfonyl group, or [5] a C 1-8  alkoxycarbonyl group, 
     (7) a C 6-10  aryl group which may be substituted by one or more R 9E , 
     R 9E : [1] a halogen atom, [2] a hydroxy group, [3] a hydroxycarbonyl group, or [4] a C 1-8  alkyl group which may be substituted by hydroxy group(s), or [5] a C 1-8  alkoxy group, 
     (8) a 5- to 14-membered heteroaryl group which may be substituted by C 1-8  alkyl group(s), 
     (9) a cyano group, 
     (10) a C 1-8  alkanoyl group, 
     (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by C 1-8  alkyl group(s), 
     (12) a halogen atom, 
     (13) a (C 1-8  alkyl) m9c -amino group which may be substituted by one or more R 9F ,
         m9c: 0˜2,       

     (14) a C 1-8  alkylcarbonyl(C 0-8  alkyl)amino group which may be substituted by (C 1-8  alkyl) m9d -amino group(s),
         m9d: 0˜2,       

     (15) a C 1-8  alkylsulfonyl(C 0-8  alkyl)amino group, 
     (16) a (C 1-8  alkyl) m9e -aminosulfonyl(C 0-8  alkyl)amino group,
         m9e: 0˜2,       

     (17) a nitro group, 
     (18) a hydroxy group, 
     (19) a C 1-8  alkoxy group which may be substituted by one or more R 9G , 
     R 9G : [1] a hydroxy group, [2] a hydroxycarbonyl group, [3] a C 6-10  aryl group which may be substituted by C 1-8  alkoxy group(s), [4] a (C 1-8  alkyl) m9g1 -amino group, [5] a C 1-8  alkoxy group which may be substituted by one or more R 9G1 , [6] a 5- to 14-membered heteroaryl group, or [7] a 4- to 10-membered heterocycloalkyloxy group which may be substituted by C 1-8  alkyl group(s),
         m9g1: 0˜2,       

     R 9G1 : [1] a C 1-8  alkoxy group, or [2] a hydroxycarbonyl group, 
     (20) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by [1] 4- to 10-membered heterocycloalkyl group(s), or [2] C 1-8  alkoxycarbonyl group(s), 
     (21) a C 1-8  alkylsulfonyloxy group which may be substituted by halogen atom(s), 
     (22) a C 1-8  alkylthio group which may be substituted by (C 1-8  alkyl) m9f -amino group(s),
         m9f: 0˜2,       

     (23) a C 1-8  alkylsulfonyl group which may be substituted by (C 1-8  alkyl) m9g -amino group(s),
         m9g: 0˜2,       

     (24) a (C 1-8  alkyl) m9h -aminosulfonyl group,
         m9h: 0˜2,       

     (25) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C 1-8  alkyl group(s), and 
     (26) a hydroxycarbonyl group]. 
     [2] The compound according to the above [1], or a salt or solvate thereof, wherein R 3  is a cyano group or a halogen atom.
 
[3] The compound according to the above [1], or a salt or solvate thereof, wherein A 5  is NR 5  and R 5  is a hydrogen atom.
 
[4] The compound according to the above [1], or a salt or solvate thereof, wherein all of the A 1 , A 2 , A 3 , A 4 , A 7 , A 8 , A 9  and A 10  are a carbon atom.
 
[5] The compound according to claim  1 , or a salt or solvate thereof, wherein: A 1 , A 2 , A 3 , A 4 , A 7 , A 8 , A 9  and A 10  all represent C, or any one of A 2 , A 3 , A 4 , A 7 , A 8  and A 9  represents N (with the proviso that, when it represents N, no substituent group exists therefor) and the remainings represent C;
 
     A 5  is selected from NR 5 , O and S; 
     R 1  represents [1] a hydrogen atom, [2] a cyano group, or [3] a halogen atom; 
     R 2  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group, 
     (3) a cyano group, 
     (4) a halogen atom, and 
     (5) a (C 1-8  alkyl) m2 -amino group which may be substituted by C 1-8  alkylsulfonyl group(s),
         m2: 0˜2;   R 3  is selected from the group consisting of:       

     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by halogen atom(s), 
     (3) a cyano group, 
     (4) a (C 1-8  alkyl) m3a -aminocarbonyl group which may be substituted by one or more R 3A , 
     R 3A : [1] a C 6-10  aryl group, [2] a C 1-8  alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C 6-10  aryl sulfonyl group,
         m3a: 0˜2,       

     (5) a hydroxycarbonyl group, 
     (6) a C 1-8  alkoxycarbonyl group which may be substituted by hydroxy group(s), 
     (7) a halogen atom, 
     (8) a (C 1-8  alkyl) m3b -amino group which may be substituted by C 6-10  aryl group(s),
         m3b: 0˜2,       

     (9) a C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group which may be substituted by [1]C 6-10  aryl group(s) or [2] C 6-10  aryloxy group(s), 
     (10) a C 6-10  arylcarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkyl group(s) which may be substituted by halogen atom(s), 
     (11) a nitro group, 
     (12) a hydroxy group, 
     (13) a C 1-8  alkoxy group which may be substituted by one or more R 3B , 
     R 3B : [1] a hydroxy group, [2] a C 1-8  alkoxy group, [3] a C 6-10  aryl (C 0-8  alkyl) aminocarbonyl group, [4] a (C 1-8  alkyl) m3d -amino group, or [5] a halogen atom,
         m3d: 0˜2,       

     (14) a 4- to 10-membered heterocycloalkyloxy group, 
     (15) a 5- to 14-membered heteroaryloxy group, 
     (16) a (C 1-8  alkyl) m3e -aminocarbonyloxy group which may be substituted by C 6-10  aryl group(s),
         m3e: 0˜2,       

     (17) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, 
     (18) a C 1-8  alkylthio group, 
     (19) a 5- to 14-membered heteroaryl group which may be substituted by C 1-8  alkyl group(s) which may be substituted by C 1-8  alkoxy group(s), 
     (20) a C 1-8  alkoxycarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkoxy group(s), 
     (21) a C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkyl group(s) which may be substituted by halogen atom(s), 
     (22) a C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group which may be substituted by C 1-8  alkoxy group(s), 
     (23) a C 3-8  cycloalkyl (C 0-8  alkyl) aminocarbonyloxy group, and 
     (24) a C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkyl group and [2] a C 1-8  alkoxy group; 
     R 4  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by halogen atom(s), 
     (3) a C 3-8  cycloalkyl group, 
     (4) a cyano group, 
     (5) an aminocarbonyl group, 
     (6) a hydroxycarbonyl group, 
     (7) a halogen atom, 
     (8) a (C 1-8  alkyl) m4b -amino group,
         m4b: 0˜2,       

     (9) a hydroxy group, and 
     (10) a C 1-8  alkoxy group which may be substituted by hydroxy group(s); 
     R 5  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more R 5A , 
     R 5A : [1] a hydroxycarbonyl group, [2] a C 1-8  alkoxycarbonyl group, [3] a hydroxy group, [4] a C 1-8  alkoxy group, [5] a (C 1-8  alkyl) m5 -amino group, or [6], a C 1-8  alkylthio group,
         m5: 0˜2, and       

     (3) a C 1-8  alkylsulfonyl group; 
     R 6  and R 6′  are each independently: 
     (1) a C 1-8  alkyl group, or 
     R 6  and R 6′  are taken together with the carbon atoms to which they are bound to form, 
     (2) a C 3-8  cycloalkyl group, or 
     (3) a 4- to 10-membered heterocycloalkyl group; 
     R 7  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a halogen atom, and 
     (3) a C 1-8  alkoxy group which may be substituted by one or more R 7A , 
     R 7A : [1] a (C 1-8  alkyl) m7a -amino group, or [2] a hydroxy group,
         m7a: 0˜2;       

     R 8  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more R 8A , 
     R 8A : [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8A1 , [2] a (C 1-8  alkyl) m8a -amino group which may be substituted by a halogen atom, and [3] a hydroxy group,
         m8a: 0˜2,       

     R 8A1 : [1] a C 1-8  alkyl group, [2] a C 1-8  alkylsulfonyl group, [3] a (C 1-8  alkyl) m8b -aminosulfonyl group, or [4] an oxo group,
         m8b: 0˜2,       

     (3) a C 2-8  alkenyl group, 
     (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B , 
     R 8B : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by one or more R 8B1 ,
 
&lt;2&gt; a C 2-8  alkynyl group,
 
&lt;3&gt; a C 3-8  cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C 1-8  alkyl group(s),
 
&lt;4&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B2 ,
 
&lt;5&gt; a C 1-8  alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkoxy group and [2] a C 3-8  cycloalkyl group,
 
&lt;6&gt; a C 1-8  alkylsulfonyl group,
 
&lt;7&gt; an oxo group,
 
&lt;8&gt; a cyano group,
 
&lt;9&gt; a C 1-8  alkanoyl group which may be substituted by one or more R 8B3 ,
 
&lt;10&gt; a C 3-8  cycloalkylcarbonyl group,
 
&lt;11&gt; a (C 1-8  alkyl) m8c -aminosulfonyl group,
 
&lt;12&gt; a C 1-8  alkylsulfonyl (C 0-8  alkyl) amino group,
 
&lt;13&gt; a (C 1-8  alkyl) m8d -amino group which may be substituted by one or more R 8B4 ,
 
&lt;14&gt; a hydroxy group, or
 
&lt;15&gt; a (C 1-8  alkyl) m8e -aminocarbonyl group,
         m8c: 0˜2,   m8d: 0˜2,   m8e: 0˜2,       

     R 8B1 : [1] a C 3-8  cycloalkyl group, [2] a hydroxy group, or [3] C 1-8  alkoxy group which may be substituted by C 1-8  alkoxy group(s), 
     R 8B2 : [1] a halogen atom, [2] a C 1-8  alkyl group, [3] an oxo group, or [4] a hydroxy group, 
     R 8B3 : a (C 1-8  alkyl) m8f -amino group,
         m8f: 0˜2,       

     R 8B4 : [1] a C 3-8  cycloalkyl group, or [2] a hydroxy group, 
     (5) a 5- to 14-membered heteroaryl group which may be substituted by a C 1-8  alkyl group, 
     (6) a (C 1-8  alkyl) m8g -aminocarbonyl group which may be substituted by one or more R 8C ,
         m8g: 0˜2,       

     R 8C : [1] a hydroxy group, [2] a (C 1-8  alkyl) m8h -amino group which may be substituted by substituent(s) selected from the group consisting of &lt;1&gt; a (C 1-8  alkyl) m8i -aminosulfonyl group and &lt;2&gt; a C 1-8  alkylsulfonyl group, or [3] a C 1-8  alkylsulfonyl group,
         m8h: 0˜2,   m8i: 0˜2,       

     (7) a 4- to 10-membered heterocycloalkyl (C 0-8  alkyl) aminocarbonyl group which may be substituted by oxo group(s), 
     (8) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R 8D , 
     R 8D : [1] a C 1-8  alkyl group which may be substituted by one or more R 8D1 , [2] a hydroxy group, or [3] a C 1-8  alkylsulfonyl group, 
     R 8D1 : [1] a hydroxy group, or [2] a C 1-8  alkoxy group, 
     (9) a hydroxycarbonyl group, 
     (10) a C 0-8  alkoxy (C 0-8  alkyl) aminocarbonyl group which may be substituted by hydroxy group(s), 
     (11) a halogen atom, 
     (12) a (C 1-8  alkyl) m8j -amino group which may be substituted by 4- to 10-membered heterocycloalkyl group(s),
         m8j: 0˜2,       

     (13) a hydroxyl group, 
     (14) a C 1-8  alkoxy group which may be substituted by one or more R 8E , 
     R 8E : 
     &lt;1&gt; a hydroxy group,
 
&lt;2&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;3&gt; a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R 8E1 ,
 
&lt;4&gt; a (C 1-8  alkyl) m8k1 -amino group which may be substituted by one or more R 8E2 ,
         m8k1: 0˜2,
 
&lt;5&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8E3 ,
 
&lt;6&gt; a 5- to 14-membered heteroaryl group,
 
&lt;7&gt; a (C 1-8  alkyl) m8k2 -aminocarbonyl group which may be substituted by one or more R 8E6 ,
   m8k2: 0˜2,
 
&lt;8&gt; a C 1-8  alkoxy group which may be substituted by one or more R 8E7 ,
 
&lt;9&gt; a C 1-8  alkylthio group,
 
&lt;10&gt; a C 1-8  alkylsulfinyl group, or
 
&lt;11&gt; a C 1-8  alkylsulfonyl group,
       

     R 8E1 : 
     &lt;1&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;2&gt; a C 1-8  alkanoyl group,
 
&lt;3&gt; a C 1-8  alkylsulfonyl group,
 
&lt;4&gt; a (C 1-8  alkyl) m8k3 -aminosulfonyl group
         m8k3: 0˜2, or
 
&lt;5&gt; a 4- to 10-membered heterocycloalkyl group,
       

     R 8E2 : 
     &lt;1&gt; a hydroxy group,
 
&lt;2&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;3&gt; a C 3-8  cycloalkyl group which may be substituted by C 1-8  alkyl group(s) which may be substituted by hydroxy group(s),
 
&lt;4&gt; a C 1-8  alkanoyl group which may be substituted by substituent(s) selected from the group consisting of [1] a (C 1-8  alkyl) m8k4 -amino group and [2] a halogen atom,
         m8k4: 0˜2,
 
&lt;5&gt; a (C 1-8  alkyl) m8k5 -aminocarbonyl group,
   m8k5: 0˜2,
 
&lt;6&gt; a C 1-8  alkylsulfonyl group,
 
&lt;7&gt; a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C 1-8  alkyl group(s),
 
&lt;8&gt; a (C 1-8  alkyl) m8k6 -aminosulfonyl group,
   m8k6: 0˜2, or       

     R 8E3 : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a hydroxy group and [2] a C 1-8  alkylcarbonyloxy group,
 
&lt;2&gt; a hydroxy group,
 
&lt;3&gt; a C 3-8  cycloalkyl group,
 
&lt;4&gt; a C 1-8  alkylsulfonyl group,
 
&lt;5&gt; a (C 1-8  alkyl) m8k8 -aminocarbonyl group,
         m8k8: 0˜2,
 
&lt;6&gt; a C 1-8  alkanoyl group which may be substituted by hydroxy group(s),
 
&lt;7&gt; an oxo group, or
 
&lt;8&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a C 1-8  alkanoyl group, and [2] a C 1-8  alkylsulfonyl group,
       

     R 8E6 : 
     &lt;1&gt; a C 2-8  alkenylcarbonyloxy group,
 
&lt;2&gt; a hydroxy group,
 
&lt;3&gt; a cyano group,
 
&lt;4&gt; a (C 1-8  alkyl) m8k9 -amino group which may be substituted by hydroxy group(s),
         m8k9: 0˜2,
 
&lt;5&gt; a C 1-8  alkoxy group which may be substituted by hydroxy group(s),
 
&lt;6&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by C 1-8  alkyl group(s), or
 
&lt;7&gt; a 5- to 14-membered heteroaryl group,
       

     R 8E7 : 
     &lt;1&gt; a hydroxy group, or
 
&lt;2&gt; a C 1-8  alkoxy group which may be substituted by hydroxy group(s),
 
     (15) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R 8F : 
     R 8F : 
     &lt;1&gt; a C 1-8  alkyl group which may be substituted by one or more R 8F1 ,
 
&lt;2&gt; a C 3-8  cycloalkyl group,
 
&lt;3&gt; a C 1-8  alkanoyl group which may be substituted by halogen atom(s),
 
&lt;4&gt; a C 1-8  alkoxycarbonyl group,
 
&lt;5&gt; a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8F2 ,
 
&lt;6&gt; a C 1-8  alkyl sulfonyl group, or
 
&lt;7&gt; a hydroxy group,
 
     R 8F1 : [1] a hydroxy group, [2] a C 1-8  alkoxy group, or [3] a halogen atom, 
     R 8F2 : [1] a 4- to 10-membered heterocycloalkyl group, [2] a C 1-8  alkoxycarbonyl group, or [3] a C 1-8  alkylsulfonyl group, 
     (16) a 5- to 14-membered heteroaryloxy group, 
     (17) a (C 1-8  alkyl) m8l1 -aminosulfonyloxy group,
         m8l1: 0˜2,       

     (18) a C 1-8  alkylthio group which may be substituted by (C 1-8  alkyl) m8l2 -amino group(s),
         m8l2: 0˜2,       

     (19) a C 1-8  alkylsulfonyl group which may be substituted by one or more R 8G , 
     R 8G : [1] a hydroxycarbonyl group, [2] a hydroxy group, or [3] a (C 1-8  alkyl) m8l3 -amino group,
         m8l3: 0˜2,       

     (20) a C 2-8  alkenyloxy group, and 
     (21) a C 1-8  alkylsulfonyloxy group which may be substituted by halogen atom(s); 
     R 9  is selected from the group consisting of: 
     (1) a hydrogen atom, 
     (2) a C 1-8  alkyl group which may be substituted by one or more R 9A , 
     R 9A : [1] a C 3-8  cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9A , [3] a hydroxy group, or [4] a C 1-8  alkoxy group, 
     R 9A1 : [1] a C 1-8  alkyl group, [2] a C 3-8  cycloalkyl group, or [3] a 4- to 10-membered heterocycloalkyl group, 
     (3) a C 2-8  alkenyl group, 
     (4) a C 2-8  alkynyl group which may be substituted by one or more R 9C , 
     R 9C : [1] a C 1-8  alkoxy group, [2] a (C 1-8  alkyl) m9b -amino group which may be substituted by C 6-10  aryl group(s), [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9C1 , [4] a C 3-8  cycloalkyl group, [5] a hydroxy group, or [6] a hydroxycarbonyl group,
         m9b: 0˜2,       

     R 9C1 : [1] a C 3-8  cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group, or [3] an oxo group, 
     (5) a C 3-8  cycloalkyl group, 
     (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9D , 
     R 9D : [1] a C 1-8  alkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), [2] a C 3-8  cycloalkyl group, [3] a 4- to 10-membered heterocycloalkyl group, or [4] a C 1-6  alkylsulfonyl group, 
     (7) a C 6-10  aryl group which may be substituted by one or more R 9E , 
     R 9E : [1] a halogen atom, [2] a hydroxy group, [3] a hydroxycarbonyl group, or [4] a C 1-8  alkyl group which may be substituted by hydroxy group(s), 
     (8) a 5- to 14-membered heteroaryl group which may be substituted by C 1-8  alkyl group(s), 
     (9) a cyano group, 
     (10) a C 1-8  alkanoyl group, 
     (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by C 1-8  alkyl group(s), 
     (12) a halogen atom, 
     (13) a (C 1-8  alkyl) m9c -amino group,
         m9c: 0˜2,       

     (14) a C 1-8  alkylcarbonyl(C 0-8  alkyl)amino group which may be substituted by (C 1-8  alkyl) m9d -amino group(s),
         m9d: 0˜2,       

     (15) a C 1-8  alkylsulfonyl(C 0-8  alkyl)amino group, 
     (16) a (C 1-8  alkyl) m9e -aminosulfonyl(C 0-8  alkyl)amino group,
         m9e: 0˜2,       

     (17) a nitro group, 
     (18) a hydroxy group, 
     (19) a C 1-8  alkoxy group which may be substituted by one or more R 9G , 
     R 9G : [1] a hydroxy group, [2] a hydroxycarbonyl group, [3] a C 6-10  aryl group which may be substituted by C 1-8  alkoxy group(s), [4] a (C 1-8  alkyl) m9g1 -amino group, [5] a C 1-8  alkoxy group which may be substituted by one or more R 9G1 , or [6] a 5- to 14-membered heteroaryl group,
         m9g1: 0˜2,       

     R 9G1 : [1] a C 1-8  alkoxy group, or [2] a hydroxycarbonyl group, 
     (20) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), 
     (21) a C 1-8  alkylthio group which may be substituted by (C 1-8  alkyl) m9f -amino group(s),
         m9f: 0˜2,       

     (22) a C 1-8  alkylsulfonyl group which may be substituted by (C 1-8  alkyl) m9g -amino group(s),
         m9g: 0˜2,       

     (23) a (C 1-8  alkyl) m9h -aminosulfonyl group,
         m9h: 0˜2, and       

     (24) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C 1-8  alkyl group(s); 
     R 10  represents [1] a hydrogen atom, or [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s)]. [6] A compound according to claim  1 , or salt or solvate thereof, which said compound is selected from the group consisting of:
     9-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-cyclopropylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-bromo-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-chloro-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   6,6,9-trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-ethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-ethynyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-cyclobutyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(1-isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(4-cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   8-(2-tert-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-ethynyl-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile;   6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; and   9-ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.
 
[7] A medicament comprising as an active ingredient the compound according to any one of the above [1] to [5], or a salt or solvate thereof.
 
[8] An ALK inhibitor comprising as an active ingredient the compound according to any one of the above [1] to [5], or a salt or solvate thereof.
 
[9] A pharmaceutical for the prophylaxis or treatment of cancer, cancer metastasis, depression or cognitive function disorder, comprising as an active ingredient the compound according to any one of the above [1] to [5], or a salt or solvate thereof.
 
[10] A pharmaceutical composition comprising the compound according to any one of the above [1] to [5], or a salt or solvate thereof and a pharmaceutically acceptable carrier(s).
 
[11] A method of treating a patient suffering from the disease including cancer, cancer metastasis, depression or cognitive function disorder, comprising administering to the patient who is in need of the treatment of the disease the compound described in any one of the above [1] to [5], salt or solvate thereof in an effective amount for the treatment of the disease.
 
[12] Use of the compound described in any one of the above [1] to [5], salt or solvate thereof in the manufacture of a pharmaceutical.
 
[13] The use according to above [11] in the manufacture of a pharmaceutical composition for the treatment or prophylaxis of the disease of mammals including human, wherein the disease is related with ALK activity.
   

     Effect of the Invention 
     The compounds of the present invention or salts or salvates thereof have an excellent activity of inhibiting ALK, excellent stability in organisms, and excellent solubility in water, and therefore are useful as a prophylactic or therapeutic agent for proliferative disorders (in particular, therapeutic agent). Further, the compounds of the present invention or salts salts or solvates thereof are useful as a prophylactic or therapeutic agent (in particular, therapeutic agent) for various diseases such as cancers including leukemia (acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphatic leukemia, chronic lymphatic leukemia and the like), malignant lymphoma (Hodgkin lymphoma, non-Hodgkin lymphoma and the like), brain tumor, neuroblastoma, gliomatosis, thyroid cancer, myelodysplastic syndrome, head and neck cancer, esophageal cancer, stomach cancer, colon cancer, colorectal cancer, breast cancer, ovarian cancer, lung cancer, pancreatic cancer, liver cancer, gall bladder cancer, skin cancer, malignant melanoma, kidney cancer, renal pelvis-ureter cancer, bladder cancer, uterine cancer, testicle cancer, prostate cancer, and the like. Further, the compounds of the present invention are useful as a prophylactic or therapeutic agent (in particular, therapeutic agent) for infiltration/metastasis of solid tumors. Still further, the compounds of the present invention are useful as a prophylactic or therapeutic agent for other diseases that are related with ALK, for example, depression or a cognitive function disorder. 
     The method of the present invention comprises a step of administering a pharmaceutically effective amount of the pharmaceutical composition comprising the compounds of the present invention or salts or solvates thereof to a patient who is in need of such treatment or suffers from such diseases or conditions. 
    
    
     MODE FOR CARRYING OUT THE INVENTION 
     Hereinbelow, the compounds of the present invention, the method of preparing the same, and the pharmaceutical agent comprising the same will be explained. 
     Definition 
     According to the present invention, the “halogen atom” means a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like. According to the present invention, when the halogen atom is a substituent group for an aromatic carbon ring, an aromatic heterocycle and the like, the preferred halogen atom includes a fluorine atom, a chlorine atom and a bromine atom. According to the present invention, when the halogen atom is a substituent group for an alkyl group or a group which comprises the alkyl as at least a part of the group (e.g., alkoxy, alkenyl, unsaturated carbocycle, unsaturated heterocycle and the like), the preferred halogen atom includes a fluorine atom. Specifically, examples thereof include a trifluoromethyl group, a pentafluoroethyl group, a heptafluoropropyl group, a nonafluorobutyl group, a trifluoromethoxy group, a pentafluoroethoxy group, a heptafluoropropoxy group, a nonafluorobutoxy group, a trifluoroacetyl group, a pentafluoropropionyl group, a heptafluorobutyryl group and a nonafluoropentanoyl group. 
     The “C 1-8  alkyl group” means a monovalent group which is derived by removing any one of hydrogen atoms from a linear or branched aliphatic hydrocarbon having 1 to 8 carbon atoms. Specifically, examples thereof include a methyl group, an ethyl group, an isopropyl group, a butyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a t-butyl group, a pentyl group, an isopentyl group, a 2,3-dimethyl propyl group, a hexyl group, a 2,3-dimethyl hexyl group, a 1,1-dimethyl pentyl group, a heptyl group and an octyl group. Preferably, it is a C 1-6  alkyl group, more preferably a C 1-5  alkyl group, still more preferably a C 1-4  alkyl group, and still even more preferably a C 1-3  alkyl group. 
     The “C 1-8  alkyl group which may be substituted” means an unsubstituted C 1-8  alkyl group or a C 1-8  alkyl group of which at least one hydrogen atom on the alkyl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl group may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkyl group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 3 substituent(s) for C 1-6  alkyl group and a C 1-4  alkyl group, and 1 to 2 substituent(s) for a C 1-3  alkyl group. 
     The “C 2-8  alkenyl group” means a monovalent group wherein at least one double bond (two adjacent SP2 carbon atoms) is comprised in a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms. Specific examples of the C 2-8  alkenyl group include a vinyl group, an allyl group, a 1-propenyl group, a 2-propenyl group, a 1-butenyl group, a 2-butenyl group (including both cis and trans), a 3-butenyl group, a pentenyl group and a hexenyl group. Preferably, it is a C 2-6  alkenyl group, more preferably a C 2-5  alkenyl group, still more preferably a C 2-4  alkenyl group, and still even more preferably a C 2-3  alkenyl group. 
     The “C 2-8  alkenyl group which may be substituted” means the unsubstituted C 2-8  alkenyl group described above or a C 2-8  alkenyl group of which at least one hydrogen atom on the alkenyl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the single-bonded carbon atom may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 2-8  alkenyl group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 3 substituent(s) for a C 2-6  alkenyl group and a C 2-4  alkenyl group, 1 to 2 substituent(s) for a C 2-3  alkenyl group. 
     The “C 2-8  alkynyl group” means a monovalent group wherein at least one triple bond (two adjacent SP carbon atoms) is comprised in a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms. Specific examples of the C 2-8  alkynyl group include an ethynyl group, a 1-propynyl group, a propargyl group and a 3-butynyl group. Preferably, it is a C 2-6  alkynyl group, more preferably a C 2-5  alkynyl group, still more preferably a C 2-4  alkynyl group, and still even more preferably a C 2-3  alkynyl group. 
     The “C 2-8  alkynyl group which may be substituted” means the unsubstituted C 2-8  alkynyl group described above or a C 2-8  alkynyl group of which at least one hydrogen atom on the alkynyl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the single-bonded carbon atom may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 2-8  alkynyl group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 3 substituent(s) for a C 2-6  alkynyl group and a C 2-4  alkynyl group, and 1 to 2 substituent(s) for C 2-3  alkynyl group. 
     The “C 3-8  cycloalkyl group” means an aliphatic hydrocarbon group in cyclic form. Preferably, it includes a C 3-6  cycloalkyl group. Specifically, examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and a cyclooctyl group. Preferably, it is a C 3-6  cycloalkyl group. 
     The “C 3-8  cycloalkyl group which may be substituted” means the unsubstituted C 3-8  cycloalkyl group described above or a C 3-8  cycloalkyl group of which at least one hydrogen atom is substituted by a defined substituent group(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the single-bonded carbon atom may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 3-8  cycloalkyl group which may be substituted by 1 to 3 substituent(s). 
     The “4- to 10-membered heterocycloalkyl group” means a saturated or partially unsaturated heterocyclic group which consists of 4 to 10 ring-constituting atoms and comprises 1 to 3 hetero atoms that are selected from O, S and N. The heterocycloalkyl group can be a monocyclic, a bicyclic or a spirocyclic type heterocycloalkyl group. Specifically, examples thereof include an oxetanyl group, a tetrahydrofuryl group, a tetrahydrothienyl group, a tetrahydropyranyl group, a pyrrolidino group, a pyrrolidinyl group, a piperidino group, a piperidinyl group, a piperazino group, a piperazinyl group, a morpholino group, a morpholinyl group, a tetrahydrothiopyranyl group, a thiomorpholino group, an imidazolidinyl group, a 1,3-dioxolanyl group, a tetrahydropyranyl group, a 1,3-dioxanyl group, a 1,2,3,6-tetrahydropyridinyl group, a 1,4-Dioxa-8-aza-spiro[4.5]decanyl group, and a 1-oxa-8-aza-spiro[4.5]decanyl group. Preferably, it is a 4- to 8-membered heterocycloalkyl group, more preferably, 4- to 6-membered heterocycloalkyl group. 
     The “4- to 10-membered heterocycloalkyl group which may be substituted” means the unsubstituted 4- to 10-membered heterocycloalkyl group described above or a 4- to 10-membered heterocycloalkyl group of which at least one hydrogen atom on the heterocycloalkyl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl group may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a 4- to 10-membered heterocycloalkyl group which may be substituted by 1 to 4 substituent(s). More preferably, it is 1 to 4 substituent(s) for a 4- to 8-membered heterocycloalkyl group, and 1 to 3 substituent(s) for a 4- to 6-membered heterocycloalkyl group. When the substituent is an oxo group, 2 oxo group can combine with the same sulfur atom. When the salt is formed, 2 alkyl group can combine with the same nitrogen atom. 
     The “C 6-10  aryl group” means a monovalent aromatic hydrocarbon ring. Specific examples of the C 6-10  aryl group include a phenyl group, a 1-naphthyl group and a 2-naphthyl group. Preferably, it is a C 6  aryl group or a C 10  aryl group. 
     The “C 6-10  aryl group which may be substituted” means the unsubstituted C 6-10  aryl group described above or a C 6-10  aryl group of which at least one hydrogen atom is substituted by a defined substituent group(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 6-10  aryl group which may be substituted by 1 to 3 substituent(s). 
     The “5- to 14-membered heteroaryl group” means an aromatic cyclic group comprising one or more hetero atoms among 5 to 14 ring-constituting atoms. The cycle can be a monocyclic or bicyclic heteroaryl group fused to a benzene ring or a monocyclic heteroaryl ring. Specific examples thereof include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group, an isooxazolyl group, an oxadiazolyl group, a thiadiazolyl group, a triazolyl group, a tetrazolyl group, a pyridyl group, a pyrimidyl group, a pyridazinyl group, a pyrazinyl group, a triazinyl group, a benzofuranyl group, a benzothienyl group, a benzothiadiazolyl group, a benzothiazolyl group, a benzoxazolyl group, a benzoxadiazolyl group, a benzoimidazolyl group, an indolyl group, an isoindolyl group, an indazolyl group, a quinolyl group, an isoquinolyl group, a cinnolinyl group, a quinazolinyl group, a quinoxalinyl group, a benzodioxolyl group, an indolizinyl group, an imidazopyridyl group and the like. Preferably, it is a 5- to 6-membered heteroaryl group. 
     The “5- to 14-membered heteroaryl group which may be substituted” means the unsubstituted 5- to 14-membered ring heteroaryl group described above or a 5- to 14-membered ring heteroaryl group of which at least one hydrogen atom on the heteroaryl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a 5- to 14-membered heteroaryl group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 3 substituent(s) or 1 to 2 substituent(s) for a 5- to 6-membered heteroaryl group. 
     The “C 1-8  alkanoyl group” means a C 1-8  alkyl-C(O)— group, and the C 1-8  alkyl group is described above. Specifically, examples thereof include acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl and a hexanoyl group. Preferably, it is a C 1-6  alkanoyl group, and more preferably a C 1-3  alkanoyl group. 
     The “C 1-8  alkanoyl group which may be substituted” means the unsubstituted C 1-8  alkanoyl group described above or a C 1-8  alkanoyl group of which at least one hydrogen atom on the alkanoyl group is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 1-8  alkanoyl group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 2 substituent(s) for a C 1-6  alkanoyl group and a C 1-3  alkanoyl group. 
     The “C 3-8  cycloalkylcarbonyl group” means a C 3-8  cycloalkyl-C(O)— group, and the C 3-8  cycloalkyl group is described above. Specifically, examples thereof include a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, a cyclohexylcarbonyl group, a cycloheptylcarbonyl group and a cyclooctylcarbonyl group. 
     The “4- to 10-membered heterocycloalkylcarbonyl group” means a 4- to 10-membered heterocycloalkyl-CO— group, and the 4- to 10-membered heterocycloalkyl is described above. 
     The “4- to 10-membered heterocycloalkylcarbonyl group which may be substituted” means the unsubstituted 4- to 10-membered heterocycloalkylcarbonyl group described above or a 4- to 10-membered heterocycloalkylcarbonyl group in which at least one hydrogen atom of the heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the heterocycloalkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a 4- to 10-membered heterocycloalkylcarbonyl group which may be substituted by 1 to 3 substituent(s). 
     The “aminocarbonyl group which may be substituted” means an unsubstituted aminocarbonyl group or an aminocarbonyl group in which one or two hydrogen atoms on the nitrogen atom are substituted by a defined substituent(s). When two substituent groups are present, each substituent group can be the same or different from each other. 
     The “C 3-8  cycloalkyl (C 0-8  alkyl) aminocarbonyloxy group” means a C 3-8  cycloalkyl-NHC(O)O— group or a C 3-8  cycloalkyl-N(C 1-8  alkyl) C(O)O— group, and the C 3-8  cycloalkyl group is described above. Specifically, examples thereof include a cyclopropylaminocarbonyloxy group, a cyclobutylaminocarbonyloxy group, a cyclopentylaminocarbonyloxy group, a cyclohexylaminocarbonyloxy group, a cyclopropyl(N-methyl)aminocarbonyloxy group, and a cyclobutyl(N-methyl)aminocarbonyloxy group. 
     The “(C 1-8  alkyl) x -aminocarbonyl group”, wherein x is a symbol defined in claims, means a NH 2 C(O)— group, a (C 1-8  alkyl)NH—C(O)— group, or a (C 1-8  alkyl) 2 N—C(O)— group. Specifically, examples thereof include a N-methyl-aminocarbonyl group, N-ethyl-aminocarbonyl group, N-n-butyl-aminocarbonyl group, a N,N-dimethyl-aminocarbonyl group. 
     The “(C 1-8  alkyl) x -aminocarbonyl group which may be substituted” means an unsubstituted (C 1-8  alkyl) x -aminocarbonyl group described above or an (C 1-8  alkyl) x -aminocarbonyl group in which at least one hydrogen atom on the nitrogen atom or the alkyl moiety are substituted by a defined substituent(s). When plural substituent groups are present, each substituent group can be the same or different from each other. 
     The “C 6-10  aryl(C 0-8  alkyl)aminocarbonyl group” means a C 6-10  aryl-NHC(O)— group, or a C 6-10  aryl-N(C 1-8  alkyl)-C(O)— group. Specifically, examples thereof include a phenyl-NHC(O)— group, or a phenyl-(N-methyl)-aminocarbonyl group, wherein the C 6-10  aryl group and C 1-8  alkyl are described above. Specifically, examples thereof include a phenylaminocarbonylamino group and a phenylaminocarbonyl(N-methyl)amino group. 
     The “4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group” means a carbonyl group to which a 4- to 10-membered nitrogen-containing heterocycloalkyl group is bonded. Herein, the 4- to 10-membered nitrogen-containing heterocycloalkyl group (i.e., 4- to 10-membered heterocycloalkyl group comprising a nitrogen atom(s)) means a heterocycloalkyl group which consists of 4 to 10 ring-constituting atoms and comprises at least one nitrogen atom as a hetero atom. Preferably, it is bonded to the carbonyl group via a nitrogen atom that is comprised in the heterocycloalkyl ring. Specific examples of the 4- to 10-membered nitrogen-containing heterocycloalkyl group include a pyrrolidinyl group, an imidazolidinyl group, a morpholino group, a thiomorpholino group, a piperazino group and a piperidino group. As for the 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, examples thereof include a pyrrolidinocarbonyl group, a piperidinocarbonyl group, a piperazinocarbonyl group and a morpholinocarbonyl group. 
     The “4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, which may be substituted” means the unsubstituted 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group as described above or a 4- to 10-membered heterocycloalkylcarbonyl group in which at least one hydrogen atom of the heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the heterocycloalkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by 1 to 3 substituent(s). 
     The “4- to 10-membered heterocycloalkyl (C 0-8  alkyl) aminocarbonyl group” means 4- to 10-membered heterocycloalkyl NHC(O)— group, or a 4- to 10-membered heterocycloalkyl N(C 1-8  alkyl)-C(O)— group. Specifically, examples thereof include a oxetan-3-yl amide group, and a (1,1-dioxo-tetrahydro-thiophen-3-yl)-amide group. 
     The “4- to 10-membered heterocycloalkyl (C 0-8  alkyl) aminocarbonyl group which may be substituted by one or more oxo groups” means the unsubstituted 4- to 10-membered heterocycloalkylaminocarbonyl group described above or the 4- to 10-membered heterocycloalkylaminocarbonyl group in which the heterocycloalkyl moiety is substituted by at least one oxo group. 
     The “C 6-10  arylsulfonyl group” means a C 6-10  aryl-S(O) 2 — group and the C 6-10  aryl group is described above. Specifically, examples thereof include a phenylsulfonyl group. 
     The “5- to 14-membered heteroarylsulfonyl group” means a 5- to 14-membered heteroaryl-S(O) 2 — group, and the 5- to 14-membered heteroaryl is described above. Specifically, examples thereof include a imidazol-sulfonyl group. 
     The “(C 1-8  alkyl) x -amino group”, wherein x is a symbol defined in claims, means an amino group, a NH(C 1-8  alkyl) group, or a N(C 1-8  alkyl) 2 — group. Specifically, examples thereof include amino, methylamino, ethylamino, butylamino, isopropylamino, dimethylamino and diethylamino. Preferably, it is a C 1-3  alkylamino group. 
     The “(C 1-8  alkyl) x -amino group which may be substituted” means an unsubstituted (C 1-8  alkyl), -amino group or an amino group in which one or two hydrogen atoms on the nitrogen atom or the alkyl moiety are substituted by a defined substituent(s). When two substituent groups are present, each substituent group can be the same or different from each other. 
     The “C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group” means a C 1-8  alkyl-C(O)—NH— group or a C 1-8  alkyl-C(O)—N(C 1-8  alkyl)- group, and the C 1-8  alkyl is described above. Specifically, examples thereof include a methylcarbonylamino group, an ethylcarbonylamino group, a propylcarbonylamino group and a butylcarbonylamino group. 
     The “C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group which may be substituted” means the unsubstituted C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group described above or the C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group in which at least one hydrogen atoms of the terminal alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkylcarbonyl (C 0-8  alkyl) amino group which may be substituted by 1 to 3 substituent(s). 
     The “C 6-10  arylcarbonyl (C 0-8  alkyl) amino group” means a C 6-10  aryl-C(O)—NH— group or a C 6-10  aryl-C(O)—N(C 1-8  alkyl)- group and the C 6-10  aryl group and the C 1-8  alkyl group are described above. Specifically, examples thereof include a phenylcarbonylamino group. 
     The “C 6-10  arylcarbonyl (C 0-8  alkyl) amino group which may be substituted” means the unsubstituted C 6-10  arylcarbonyl (C 0-8  alkyl) amino group described above or the C 6-10  arylcarbonyl (C 0-8  alkyl) amino group in which at least one hydrogen atoms of the aryl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 6-10  arylcarbonyl (C 0-8  alkyl) amino group which may be substituted by 1 to 3 substituent(s). 
     The “(C 1-8  alkyl) x -aminocarbonyl (C 0-8  alkyl) amino group”, wherein x is a symbol defined in claims, means a NH 2 C(O)NH— group, a (C 1-8  alkyl)NHC(O)NH— group, a NH 2 C(O)N(C 1-8  alkyl)- group, or a (C 1-8  alkyl)NHC(O)N(C 1-8  alkyl)- group, and the C 1-8  alkyl is described above. Specifically, examples thereof include aminocarbonyl-(N-methyl)amino, and (N-methyl)aminocarbonyl-(N′-methyl)amino. 
     The “(C 1-8  alkyl) x -aminocarbonyl (C 0-8  alkyl) amino group which may be substituted” means an unsubstituted (C 1-8  alkyl) x -aminocarbonyl (C 0-8  alkyl) amino group, or a (C 1-8  alkyl) x -aminocarbonyl (C 0-8  alkyl) amino group in which at least one hydrogen atom on the nitrogen atom or the alkyl moiety is substituted by a defined substituent. Preferably, it is a (C 1-8  alkyl) x -aminocarbonyl (C 0-8  alkyl) amino group which may be substituted by a phenyl group. 
     The “C 1-8  alkylsulfonylamino group” means a C 1-8  alkyl-S(O) 2 —NH— group and the C 1-6  alkyl group is described above. Specifically, examples thereof include a methylsulfonylamino group and an ethylsulfonylamino group. 
     The “(C 1-8  alkyl) x -aminosulfonyl(C 0-8  alkyl)amino group”, wherein x is a symbol defined in claims, means a NH 2 S(O) 2 NH— group, a NH(C 1-8  alkyl)-S(O) 2 NH— group, or a N(C 1-8  alkyl) 2 -S(O) 2 NH— group, a NH 2 S(O) 2 N(C 1-8  alkyl)- group, a NH(C 1-8  alkyl)-S(O) 2  (C 1-8  alkyl)N— group, or a N(C 1-8  alkyl) 2 -S(O) 2  (C 1-8  alkyl)N— group, and the C 1-8  alkyl group is described above. Specifically, examples thereof include a methylamino-sulfonylamino group and a dimethylamino-sulfonylamino group. 
     The “C 1-8  alkoxy group” means a C 1-8  alkyl-O— group. Specifically, examples thereof include a methoxy group, an ethoxy group, a 1-propoxy group, a 2-propoxy group, a n-butoxy group, an i-butoxy group, a sec-butoxy group, a t-butoxy group, a 1-pentyloxy group, a 2-pentyloxy group, a 3-pentyloxy group, a 2-methyl-1-butyloxy group, a 3-methyl-1-butyloxy group, a 2-methyl-2-butyloxy group, a 3-methyl-2-butyloxy group, a 2,2-dimethyl-1-propyloxy group, a 1-hexyloxy group, a 2-hexyloxy group, a 3-hexyloxy group, a 2-methyl-1-pentyloxy group, a 3-methyl-1-pentyloxy group, a 4-methyl-1-pentyloxy group, a 2-methyl-2-pentyloxy group, a 3-methyl-2-pentyloxy group, a 4-methyl-2-pentyloxy group, a 2-methyl-3-pentyloxy group, a 3-methyl-3-pentyloxy group, a 2,3-dimethyl-1-butyloxy group, a 3,3-dimethyl-1-butyloxy group, a 2,2-dimethyl-1-butyloxy group, a 2-ethyl-1-butyloxy group, a 3,3-dimethyl-2-butyloxy group, a 2,3-dimethyl-2-butyloxy group and a 1-methyl-cyclopropylmethoxy group. Preferably, it is a C 1-6  alkoxy group, more preferably a C 1-5  alkoxy group, still more preferably a C 1-4  alkoxy group, and still even more preferably a C 1-3  alkoxy group. 
     The “C 1-8  alkoxy group which may be substituted” means an unsubstituted C 1-8  alkoxy group or a C 1-8  alkoxy group in which at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkoxy group which may be substituted by 1 to 3 substituent(s). More preferably, it is 1 to 3 substituent(s) for C 1-6  alkoxy group and a C 1-4  alkoxy group, and 1 to 2 substituent(s) for a C 1-3  alkoxy group. 
     The “C 1-8  alkoxycarbonyl group” means a C 1-8  alkyl-O—C(O)— group and the C 1-8  alkyl group is described above. Specifically, examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, a n-propoxycarbonyl group and an i-propoxycarbonyl group. Preferably, it is a C 1-6  alkoxycarbonyl group, and more preferably a C 1-3  alkoxycarbonyl group. 
     The “C 1-8  alkoxycarbonyl group which may be substituted” means the unsubstituted C 1-8  alkoxycarbonyl group described above or a C 1-8  alkoxycarbonyl group of which at least one hydrogen atom is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety of the alkoxycarbonyl group may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkoxycarbonyl group which may be substituted by 1 to 3 substituent(s). 
     The “C 0-8  alkoxy (C 0-8  alkyl) aminocarbonyl group” means a HO—NH—C(O)— group, a C 1-8  alkyl-NH—C(O)— group, a HO—N(C 1-8  alkyl)-C(O)— group, or a C 1-8  alkyl-N(C 1-8  alkyl)-C(O)— group, and has a C 1-8  alkoxy group or a C 1-8  alkyl group as described above. Specifically, examples thereof include a methoxyaminocarbonyl group, an ethoxyaminocarbonyl group, a n-propoxyaminocarbonyl group and an i-propoxyaminocarbonyl group. Preferably, it is a C 1-6  alkoxyaminocarbonyl group, and more preferably a C 1-3  alkoxyaminocarbonyl group. 
     The “C 0-8  alkoxy (C 0-8  alkyl) aminocarbonyl group which may be substituted” means the unsubstituted hydroxyaminocarbonyl group described above, or a C 1-8  alkoxyaminocarbonyl group, a hydroxy (C 1-8  alkyl) aminocarbonyl group or a C 1-8  alkoxy (C 1-8  alkyl) aminocarbonyl group, wherein at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkoxy aminocarbonyl group which may be substituted by 1 to 3 substituent(s). 
     The “4- to 10-membered heterocycloalkyloxy group” means a 4- to 10-membered heterocycloalkyl-O— group, and the 4- to 10-membered heterocycloalkyl is described above. 
     The “4- to 10-membered heterocycloalkyloxy group which may be substituted” means the unsubstituted 4- to 10-membered heterocycloalkyloxy group described above or a 4- to 10-membered heterocycloalkyloxy group in which at least one hydrogen atom of the heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the heterocycloalkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a 4- to 10-membered heterocycloalkyloxy group which may be substituted by 1 to 3 substituent(s). 
     The “C 6-10  aryloxy group” means a C 6-10  aryl-O— group, and the C 6-10  aryl group is described above. 
     The “5- to 14-membered heteroaryloxy group” means a 5- to 14-membered heteroaryl-O— group, and the 5- to 14-membered heteroaryl is described above. Specifically, examples thereof include a pyrimidinyloxy group. 
     The “C 1-8  alkylcarbonyloxy group” means a C 1-8  alkyl-C(O)—O— group, and the C 1-8  alkyl is described above. Specifically, examples thereof include a methylcarbonyloxy group, an ethylcarbonyloxy group and a propylcarbonyloxy group. 
     The “C 2-8  alkenylcarbonyloxy group” means a C 2-8  alkenyl-C(O)—O— group, and the C 2-8  alkenyl is described above. Specifically, examples thereof include a 2-methyl-2-butenoyloxy group. 
     The “4- to 10-membered heterocycloalkylcarbonyloxy group” means a 4- to 10-membered heterocycloalkyl-C(O)—O— group, and the 4- to 10-membered heterocycloalkyl is described above. 
     The “(C 1-8  alkyl) x -aminocarbonyloxy group”, wherein x is a symbol defined in claims, means a NH 2 C(O)—O— group, a NH(C 1-8  alkyl)-C(O)—O— group, or a N(C 1-8  alkyl) 2 -C(O)—O— group. Specifically, examples thereof include a methylamino-carbonyloxy group, an ethylamino-carbonyloxy group and a propylamino-carbonyloxy group. 
     The “(C 1-8  alkyl) x -aminocarbonyloxy group which may be substituted” means an unsubstituted (C 1-8  alkyl) x -aminocarbonyloxy group or a (C 1-8  alkyl) x -aminocarbonyloxy group in which one or two hydrogen atoms on the nitrogen atom or the alkyl moiety are substituted by a defined substituent(s). When two substituent groups are present, each substituent group can be the same or different from each other. 
     The “4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group” means the 4- to 10-membered nitrogen-containing heterocycloalkyl-S(O) 2 — group described above. Specifically, examples thereof include a morpholino-sulfonyl group. 
     The “4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted” means the unsubstituted 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group described above or the 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group in which at least one hydrogen atom of the 4- to 10-membered nitrogen-containing heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl which may be substituted by 1 to 3 substituent(s). 
     The “4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group” means the 4- to 10-membered nitrogen-containing heterocycloalkyl-S(O) 2 —O— group described above. Specifically, examples thereof include a morpholino-sulfonyloxy group and a piperadino-sulfonyloxy group. 
     The “4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group which may be substituted” means the unsubstituted 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group described above or the 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group in which at least one hydrogen atom of the 4- to 10-membered nitrogen-containing heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy which may be substituted by 1 to 3 substituent(s). 
     The “C 1-8  alkylsulfonyloxy group” means a C 1-8  alkyl-S(O) 2 —O— group, and the C 1-8  alkyl is described above. 
     The “C 1-8  alkylsulfonyloxy group which may be substituted” means the unsubstituted C 1-8  alkylsulfonyloxy group described above or a C 1-8  alkylsulfonyloxy group in which at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkylsulfonyloxy group which may be substituted by 1 to 3 substituent(s). Specifically, examples thereof include a trifluoromethylsulfonyloxy group. 
     The “(C 1-8  alkyl) x -aminosulfonyloxy group” wherein x is a symbol defined in claims, means a NH 2 S(O) 2 — group, a N(C 1-8  alkyl)S(O) 2 — group, or a N(C 1-8  alkyl) 2 S(O) 2 — group. Specifically, examples thereof include a N-methylaminosulfonyloxy group. 
     The “C 1-8  alkylthio group” means a C 1-8  alkyl-S— group, and the C 1-8  alkyl group is described above. Examples thereof include methylthio, ethylthio, n-propylthio, i-propylthio, n-butylthio, s-butylthio, i-butylthio, t-butylthio, n-pentylthio, 3-methylbutylthio, 2-methylbutylthio, 1-methylbutylthio, 1-ethylpropylthio, n-hexylthio, 4-methylpentylthio, 3-methylpentylthio, 2-methylpentylthio, 1-methylpentylthio, 3-ethylbutylthio, and 2-ethylbutylthio and the like. Preferably, it is a C 1-6  alkylthio group, and more preferably a C 1-3  alkylthio group. 
     The “C 1-8  alkylthio group which may be substituted” means an unsubstituted C 1-8  alkylthio group or a C 1-8  alkylthio group in which at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the alkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a C 1-8  alkylthio group which may be substituted by 1 to 3 substituent(s). 
     The “C 1-8  alkylsulfonyl group” means a C 1-8  alkyl-S(O) 2 — group, and the C 1-8  alkyl group is described above. Specifically, examples thereof include a methylsulfonyl group, an ethylsulfonyl group and a n-propylsulfonyl group. Preferably, it is a C 1-6  alkylsulfonyl group, and more preferably a C 1-3  alkylsulfonyl group. 
     The “C 1-8  alkylsulfinyl group” means a C 1-8  alkyl-S(O)— group, and the C 1-8  alkyl group is described above. Specifically, examples thereof include a methylsulfinyl group, an ethylsulfinyl group and a n-propylsulfinyl group. Preferably, it is a C 1-6  alkylsulfinyl group, and more preferably a C 1-3  alkylsulfinyl group. 
     The “C 1-8  alkylsulfonyl group which may be substituted” means the unsubstituted C 1-8  alkylsulfonyl group described above or a C 1-8  alkylsulfonyl group in which at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 1-8  alkylsulfonyl group which may be substituted by 1 to 3 substituent(s). 
     The “C 1-8  alkylsulfinyl group which may be substituted” means the unsubstituted C 1-8  alkylsulfinyl group described above or a C 1-8  alkylsulfinyl group in which at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 1-8  alkylsulfinyl group which may be substituted by 1 to 3 substituent(s). 
     The “4- to 10-membered heterocycloalkylsulfonyl group” means a 4- to 10-membered heterocycloalkyl-S(O) 2 — group, and the 4- to 10-membered heterocycloalkyl is described above. 
     The “4- to 10-membered heterocycloalkylsulfonyl group which may be substituted” means the unsubstituted 4- to 10-membered heterocycloalkylsulfonyl group described above or a 4- to 10-membered heterocycloalkylsulfonyl group in which at least one hydrogen atom of the heterocycloalkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. In addition, the heterocycloalkyl moiety may be substituted by a cyclic substituent group through a spiro bond. Preferably, it is a 4- to 10-membered heterocycloalkylsulfonyl group which may be substituted by 1 to 3 substituent(s). 
     The “(C 1-8  alkyl) x -aminosulfonyl group”, wherein x is a symbol defined in claims, means a NH 2 —S(O) 2 — group, a C 1-8  alkylamino-S(O) 2 — group, or a (C 1-8  alkyl) 2 amino-S(O) 2 — group and the C 1-8  alkyl is described above. Specifically, examples thereof include an aminosulfonyl group, a methylaminosulfonyl group and a dimethylaminosulfonyl group. 
     The “(C 1-8  alkyl) x -aminosulfonyl group which may be substituted” means an unsubstituted aminosulfonyl group or a (C 1-8  alkyl), -aminosulfonyl group in which one or two hydrogen atoms on the nitrogen atom or the alkyl moiety are substituted by a defined substituent(s). When two substituent groups are present, each substituent group can be the same or different from each other. 
     The “C 1-8  alkoxycarbonyl (C 0-8  alkyl) amino group” means a C 1-8  alkoxy-C(O)—NH— group or a C 1-8  alkoxy-C(O)—N(C 1-8  alkyl)- group, wherein the C 1-8  alkoxy group and C 1-8  alkyl) are described above. Specifically, examples thereof include a methoxycarbamoyl group and an N-ethylcarbonyl-N-methyl-amino group. 
     The “C 1-8  alkoxycarbony(C 0-8  alkyl) amino group which may be substituted” means the unsubstituted C 1-8  alkoxycarbony(C 0-8  alkyl) amino group described above, or a C 1-8  alkoxycarbony(C 0-8  alkyl) amino group, wherein at least one hydrogen atom of the alkyl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 1-8  alkoxycarbony(C 0-8  alkyl) amino group which may be substituted by 1 to 3 substituent(s). 
     The “C 1-8  alkoxycarbonyl (C 0-8  alkyl) aminosulfonyl group” means a C 1-8  alkoxy-C(O)—NHS(O) 2 — group or a C 1-8  alkoxy-C(O)—N(C 1-8  alkyl)S(O) 2 — group, wherein the C 1-8  alkoxy group and C 1-8  alkyl group are described above. Specifically, examples thereof include a methoxycarbonylaminosulfonyl group and an ethoxycarbonyl-N-methyl-aminosulfonyl group. 
     The “C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group” means a C 6-10  aryl-O—C(O)—NH— group or a C 6-10  aryl-O—C(O)—N(C 1-8  alkyl)- group, wherein the C 6-10  aryl group and C 1-8  alkyl are described above. Specifically, examples thereof include a phenyloxycarbonylamino group and a N-methyl-N-phenyloxycarbonyl-amino group. 
     The “C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group which may be substituted” means the unsubstituted C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group described above or the C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group in which at least one hydrogen atoms of the aryl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 6-10  aryloxycarbonyl (C 0-8  alkyl) amino group which may be substituted by 1 to 3 substituent(s). 
     The “C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group” means a C 6-10  aryl NHC(O)NH— group, a C 6-10  aryl-N(C 1-8  alkyl)-C(O)NH— group, a C 6-10  aryl-N(C 1-8  alkyl)-C(O)N(C 1-8  alkyl)- group, or a C 6-10  aryl-NH—C(O)N(C 1-8  alkyl)- group, wherein the C 6-10  aryl group and C 1-8  alkyl are described above. Specifically, examples thereof include a phenylaminocarbonylamino group and a phenylaminocarbonyl(N-methyl)amino group. 
     The “C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group which may be substituted” means the unsubstituted C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group described above or the C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group in which at least one hydrogen atoms of the aryl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 6-10  aryl (C 0-8  alkyl) aminocarbonyl (C 0-8  alkyl) amino group which may be substituted by 1 to 3 substituent(s). 
     The “C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group” means a C 6-10  aryl-NHC(O)—O—, or a C 6-10  aryl-N(C 1-8  alkyl)-C(O)—O— group, wherein the C 6-10  aryl group and C 1-8  alkyl are described above. Specifically, examples thereof include a phenylaminocarbonyloxy group and a phenylaminocarbonyl(N-methyl)amino carbonyloxy group. 
     The “C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group which may be substituted” means the unsubstituted C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group described above or the C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group in which at least one hydrogen atoms of the aryl moiety is substituted by a defined substituent(s). When two or more substituent groups are present, each substituent group can be the same or different from each other. Preferably, it is a C 6-10  aryl (C 0-8  alkyl) aminocarbonyloxy group which may be substituted by 1 to 3 substituent(s). 
     The “C 1-8  alkylsulfonyl (C 0-8  alkyl) amino group” means a C 1-8  alkyl-S(O) 2 —NH— group, or a C 1-8  alkyl-S(O) 2 —N(C 1-8  alkyl)- group. Specifically, examples thereof include a methylsulphonylamino group and a methylsulphonyl-(N-methyl)amino group. 
     The “C 2-8  alkenyloxy group” means a C 2-8  alkenyl-O— group, wherein the C 2-8  alkenyl group is described above. Specific examples of the C 2-8  alkenyloxy group include a vinyloxy group and a allyloxy group. 
     Preferably, all of A 1 , A 2 , A 3 , A 4 , A 7 , A 8 , A 9  and A 10  are C, or any one of A 2 , A 4 , A 7  and A 9  is N and the remainings are C (with the proviso that, when A 2 , A 4 , A 7  or A 9  is N, they do not have a substituent group R 2 , R 4 , R 7  or R 9 ). More preferably, all of them are C, or A 4  is N while the remainings are C, even more preferably, all of them are C, or A 4 , A 7 , and A 9  is N and the remainings are C (with the proviso that, when A 4 , A 7 , or A 9  is N, they do not have a substituent group R 4 , R 7 , R 9 ). 
     A 5  is preferably NR 5  or O, more preferably NR 5 , even more preferably NH. 
     R 1  is preferably 
     [1] a hydrogen atom,
 
[2] a halogen atom,
 
and more preferably
 
[1] a hydrogen atom,
 
[2] a fluorine atom,
 
[3] a chlorine atom.
 
     R 10  is preferably a hydrogen atom. 
     R 2  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-5  alkyl group,
 
[3] a cyano,
 
[4] a halogen atom,
 
and more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group,
 
[3] a fluorine atom,
 
[4] a chlorine atom,
 
[5] a bromine atom.
 
And even more preferably
 
[1] a hydrogen atom,
 
[2] a halogen atom,
 
Still more preferably
 
[1] a hydrogen atom,
 
     R 4  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-5  alkyl group which may be substituted by 1-11 halogen atom(s),
 
[3] a C 3-6  cycloalkyl group,
 
[4] a cyano,
 
[5] a halogen atom,
 
[6] a (C 1-3  alkyl)m4b-amino group (m4b: 0˜2),
 
[7] a hydroxy,
 
[8] a C 1-5  alkoxy group which may be substituted by 1-4 hydroxy(s),
 
and more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-7 halogen atom(s),
 
[3] a C 3-5  cycloalkyl group,
 
[4] a cyano,
 
[5] a fluorine atom,
 
[6] a bromine atom,
 
[7] an amino (C 1-3  alkyl)m4b-amino group,
 
[8] a hydroxy,
 
[9] a C 1-3  alkoxy group which may be substituted by 1-2 hydroxy(s).
 
Even more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by at least one halogen atom,
 
[3] a C 3-8  cycloalkyl group,
 
[4] a cyano,
 
[5] a halogen atom,
 
[6] a hydroxy,
 
[7] a C 1-8  alkoxy group which may be substituted by a hydroxy,
 
Still more preferably
 
[1] a hydrogen atom,
 
[2] a halogen atom,
 
     R 5  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-5  alkyl group which may be substituted by 1-5 R 5A  substituent(s),
 
[3] a C 1-5  alkylsulfonyl group,
 
and more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-3 R 5A  substituent(s),
 
[3] a C 1-3  alkylsulfonyl group.
 
Even more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-8  alkyl group,
 
Still more preferably
 
[1] a hydrogen atom.
 
     R 5A  is preferably 
     [1] a C 1-8  alkoxycarbonyl group,
 
[2] a hydroxy,
 
[3] a C 1-8  alkoxy group,
 
[4] a (C 1-5  alkyl) m5 -amino group (m5: 0-2),
 
[5] a C6 aryl,
 
[6] a C 1-8  alkylthio group,
 
and more preferably
 
[1] a C 1-3  alkoxycarbonyl group,
 
[2] a hydroxy,
 
[3] a C 1-3  alkoxy group,
 
[4] a (C 1-3  alkyl) m5 -amino group (m5: 0-2),
 
[5] a C 1-3  alkylthio group,
 
even more preferably
 
[1] a hydroxy,
 
[2] a C 1-8  alkoxy group,
 
[3] a (C 1-8  alkyl) m5 -amino group (m5: 0-2),
 
[4] a C 1-8  alkylthio group.
 
     R 6  and R 6′  are preferably 
     [1] a C 1-8  alkyl group,
 
taken together with carbon atoms to which they are bound to form
 
[2] a C 3-8  cycloalkyl group,
 
[3] a 4- to 10-membered heterocycloalkyl group,
 
more preferably
 
[1] a C 1-3  alkyl group,
 
taken together with carbon atoms to which they are bound to form
 
[2] a C 3-6  cycloalkyl group,
 
[3] a 4- to 6-membered heterocycloalkyl group,
 
even more preferably
 
[1] a methyl,
 
taken together with carbon atoms to which they are bound to form
 
[2] a cyclopentane,
 
[3] a tetrahydropyran,
 
[4] or a piperidine.
 
     R 7  is preferably 
     [1] a hydrogen atom,
 
[2] a fluorine atom,
 
[3] a bromine atom,
 
[4] a chlorine atom,
 
[5] a C 1-5  alkoxy group which may be substituted by 1-4 R 7A  substituent(s),
 
and more preferably
 
[1] a hydrogen atom,
 
[2] a halogen atom,
 
and even more preferably
 
[1] a hydrogen atom,
 
[2] a fluorine atom,
 
[3] a bromine atom,
 
[4] a chlorine atom,
 
and still more preferably
 
[1] a hydrogen atom.
 
     R 7A  is preferably 
     [1] a (C 1-5  alkyl)m7-amino group (m7: 0-2),
 
[2] a hydroxy,
 
[3] a 4- to 6-membered heterocycloalkyl group which may be substituted by C 1-8  alkyl group(s), and more preferably
 
[1] a (C 1-3  alkyl)m7-amino group (m7: 2),
 
[2] a hydroxy,
 
[3] a 4- to 6-membered heterocycloalkyl group which may be substituted by C 1-3  alkyl group(s).
 
     R 3  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by 1-11 halogen atom(s),
 
[3] a cyano,
 
[4] a (C 1-8  alkyl) m3a -aminocarbonyl group (m3a: 0˜2) which may be substituted by 1-5 R 3A  substituents,
 
[5] a hydroxycarbonyl,
 
[6] a C 1-8  alkylcarbonyl group which may be substituted by 1-4 hydroxy(s),
 
[7] a halogen atom,
 
[8] a (C 1-3  alkyl) m3b -amino group (m3b: 0˜2) which may be substituted by 1-2 C 6  aryl(s),
 
[9] a C 1-8  alkyl carbonyl (C 0-3  alkyl) amino group which may be substituted by 1-2 C 6  aryl(s) or 1-2 C 6  aryloxy(s),
 
[10] a C 6  arylcarbonyl (C 0-3  alkyl) amino group which may be substituted by 1-5 C 1-3  alkyl group(s) which may be substituted by 1-7 halogen atom(s),
 
[11] a (C 1-3  alkyl) m3c -aminocarbonyl(C 0-3  alkyl) amino group (m3c: 0-1) which may be substituted by a C 6  aryl,
 
[12] a nitro,
 
[13] a hydroxy,
 
[14] a C 1-8  alkoxy group which may be substituted by 1-4 R 3B (s),
 
[15] a 4- to 6-membered heterocycloalkyloxy group,
 
[16] a 6-membered heteroaryloxy,
 
[17] a (C 1-5  alkyl) m3e -aminocarbonyloxy group (m3e: 0˜2) which may be substituted by 1-3 C 6  aryl(s),
 
[18] a 4- to 6-membered nitrogen-containing heterocycloalkylaminocarbonyl group,
 
[19] a C 1-8  alkylthio group,
 
[20] a 5- to 6-membered heteroaryl group which may be substituted by 1-4 C 1-8  alkyl group(s) which may be substituted by 1-3 C 1-8  alkoxy group(s),
 
[21] a C 1-3  alkoxycarbonyl (C 0-3  alkyl) amino group which may be substituted by a C 1-3  alkoxy group,
 
[22] a C 6  aryloxycarbonyl (C 0-3  alkyl) amino group which may be substituted by 1-3 C 1-3  alkyl group(s) which may be substituted by 1-9 halogen atom(s),
 
[23] a C 6  aryloxycarbonyl (C 0-3  alkyl) aminocarbonyl (C 0-3  alkyl)amino group which may be substituted by 1-3 R 3C ,
 
[24] a C 3-6  cycloalkyl (C 0-3  alkyl) aminocarbonyloxy group, and
 
[25] a C 6  aryl (C 0-3  alkyl) aminocarbonyloxy group which may be substituted by 1-3 substituent(s) selected from the group consisting of a C 1-8  alkyl group and a C 1-8  alkoxy group(s).
 
     R 3  is more preferably 
     [1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-7 halogen atom(s),
 
[3] a cyano,
 
[4] a (C 1-4  alkyl) m3a -aminocarbonyl group (m3a: 0-1) which may be substituted by 1-4 R 3A  substituents,
 
[5] a hydroxycarbonyl,
 
[6] a halogen atom,
 
[7] a C 1-4  alkyl carbonyl (C 1-3  alkyl) amino group which may be substituted by 1-2 C 6  aryl(s) or 1-2 C 6  aryloxy(s),
 
[8] a C 6  arylcarbonyl (C 0-3  alkyl) amino group which may be substituted by a C 1-3  alkyl group which may be substituted by 1-7 halogen atom(s),
 
[9] a nitro,
 
[10] a hydroxy,
 
[11] a C 1-4  alkoxy group which may be substituted by 1-3 R 3B  substituent(s),
 
[12] a 4-membered heterocycloalkyloxy group,
 
[13] a (C 1-3  alkyl) m3e -aminocarbonyloxy group (m3e:1) which may be substituted by a C 6  aryl(s),
 
[14] a 6-membered nitrogen-containing heterocycloalkylaminocarbonyl group,
 
[15] a C 1-3  alkylthio group,
 
[16] a 5-membered heteroaryl group which may be substituted by a C 1-5  alkyl group which may be substituted by a C 1-3  alkoxy group,
 
[17] a C 6  aryloxycarbonyl (C 0-3  alkyl) aminocarbonyl (C 0-3  alkyl)amino group which may be substituted by a R 3C  substituent,
 
[18] a C 6  cycloalkyl (C 0-2  alkyl) aminocarbonyloxy group, and
 
[19] a C 6  aryl (C 0-3  alkyl) aminocarbonyloxy group which may be substituted by 1-2 substituent(s) selected from the group consisting of a C 1-4  alkyl group and a C 1-3  alkoxy group.
 
     R 3  is still more preferably 
     [1] a hydrogen atom,
 
[2] a cyano,
 
[3] a halogen atom,
 
     R 3  is still even more preferably 
     [1] a cyano,
 
[2] a halogen atom.
 
     R 3A  is preferably 
     [1] a C 6  aryl,
 
[2] a C 1-5  alkoxy group,
 
[3] a 5- or 6-membered heteroaryl group,
 
[4] a C 6  arylsulfonyl.
 
     R 3B  is preferably 
     [1] a hydroxy,
 
[2] a C 1-5  alkoxy group,
 
[3] a C 6  aryl (C 0-3  alkyl) aminocarbonyl group,
 
[4] a (C 1-3  alkyl) m3a -amino group (m3d: 0˜2),
 
[5] a halogen atom,
 
more preferably
 
[1] a hydroxy,
 
[2] a C 1-8  alkoxy group.
 
     R 3C  is preferably 
     [1] a C 1-8  alkyl group which may be substituted by 1-11 halogen atom(s),
 
[2] a C 1-8  alkoxy group,
 
more preferably
 
[1] a C 1-4  alkyl group which may be substituted by 1-9 halogen atom(s),
 
[2] a C 1-3  alkoxy group.
 
     R 8  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by 1-5 R 8A  substituent(s),
 
[3] a C 2-8  alkenyl group,
 
[4] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-4 R 8B , substituent(s),
 
[5] a 5- to 6-membered heteroaryl group which may be substituted by 1-4 C 1-8  alkyl group(s),
 
[6] a (C 1-5  alkyl) m8g -aminocarbonyl group (m8g: 0˜2) which may be substituted by 1-3 R 8C  substituent(s),
 
[7] a 4- to 6-membered heterocycloalkyl (C 0-3  alkyl) aminocarbonyl group which may be substituted by 1-2 oxo group(s),
 
[8] a 4- to 6-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by 1-4 R 8D  substituent(s),
 
[9] a hydroxycarbonyl,
 
[10] a C 1-8  alkoxy (C 0-3  alkyl) aminocarbonyl group which may be substituted by 1-3 hydroxy group(s),
 
[11] a halogen atom,
 
[12] a (C 1-8  alkyl)m8j-amino group (m8j: 0˜2) which may be substituted by 1-2 R 8H  substituent(s),
 
[13] a hydroxyl,
 
[14] a C 1-5  alkoxy group which may be substituted by 1-4 R 8E  substituent(s),
 
[15] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by 1-5 R 8F , substituent(s),
 
[16] a 6-membered heteroaryloxy group,
 
[17] a (C 1-5  alkyl) m8l1 -aminosulfonyloxy group (m8l1:0-2),
 
[18] a C 1-5  alkyl thio group which may be substituted by 1-4 R 8I  substituent(s),
 
[19] a C 1-5  alkylsulfonyl group which may be substituted by 1-4 R 8G  substituent(s),
 
[20] a 6-membered heterocycloalkylsulfonyl group which may be substituted by a C 1-3  alkyl group,
 
[21] a C 2-5  alkenyloxy group, and
 
[22] a C 1-3  alkylsulfonyloxy group which may be substituted by 1-7 halogen atom(s).
 
And more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-3 R 8A  substituent(s),
 
[3] a C 2-4  alkenyl group,
 
[4] a 6-membered heterocycloalkyl group which may be substituted by 1-3 R 8B , substituent(s),
 
[5] a 5- to 6-membered heteroaryl group which may be substituted by 1-2 C 1-3  alkyl group(s),
 
[6] a (C 1-3  alkyl) m8g -aminocarbonyl group (m8g: 0˜2) which may be substituted by 1-2 R 8C  substituent(s),
 
[7] a 4- to 6-membered heterocycloalkyl (C 0-1  alkyl) aminocarbonyl group which may be substituted by 1-2 oxo group(s),
 
[8] a 6-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by 1-2 R 8D  substituent(s),
 
[9] a hydroxycarbonyl,
 
[10] a C 1-3  alkoxy (C 0-3  alkyl) aminocarbonyl group which may be substituted by 1-2 hydroxy group(s),
 
[11] a bromine atom,
 
[12] a (C 1-3  alkyl)m8j-amino group (m8j: 0˜2) which may be substituted by 1-2 R 8H  substituent(s),
 
[13] a hydroxyl,
 
[14] a C 1-5  alkoxy group which may be substituted by 1-3 R 8E  substituent(s),
 
[15] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by 1-3 R 8F , substituent(s),
 
[16] a 6-membered heteroaryloxy group,
 
[17] a (C 1-3  alkyl) m8l1 -aminosulfonyloxy group (m8l1:0-2),
 
[18] a C 1-3  alkyl thio group which may be substituted by 1-2 R 8I  substituent(s),
 
[19] a C 1-3  alkylsulfonyl group which may be substituted by 1-2 R 8G  substituent(s),
 
[20] a 6-membered heterocycloalkylsulfonyl group which may be substituted by a C 1-3  alkyl group,
 
[21] a C 2-3  alkenyloxy group, and
 
[22] a trifluoromethylsulfonyloxy group, Even more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-3 R 8A  substituent(s),
 
[3] a 6-membered heterocycloalkyl group which may be substituted by 1-3 R 8B , substituent(s),
 
[4] a 5- to 6-membered heteroaryl group which may be substituted by 1-2 C 1-3  alkyl group(s),
 
[5] a 4- to 6-membered heterocycloalkyl (C0-1 alkyl) aminocarbonyl group which may be substituted by 1-2 oxo group(s),
 
[6] a 6-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by 1-2 R 8D  substituent(s),
 
[7] a (C 1-3  alkyl) m8j -amino group (m8j: 0˜2) which may be substituted by 1-2 R 8H  substituent(s),
 
[8] a hydroxyl,
 
[9] a C 1-5  alkoxy group which may be substituted by 1-3 R 8E  substituent(s),
 
[10] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by 1-3 R 8F , substituent(s),
 
[11] a 6-membered heteroaryloxy group,
 
[12] a C 1-3  alkyl thio group which may be substituted by 1-2 R 8I  substituent(s),
 
[13] a C 1-3  alkylsulfonyl group which may be substituted by 1-2 R 8G  substituent(s), and
 
[14] a C 2-3  alkenyloxy group,
 
further preferably
 
[1] a hydrogen atom,
 
[2] a C 1-3  alkyl group which may be substituted by 1-3 R 8A  substituent(s),
 
[3] a 6-membered heterocycloalkyl group which may be substituted by 1-3 R 8B , substituent(s),
 
[4] a (C 1-3  alkyl) m8j -amino group (m8j: 0˜2) which may be substituted by 1-2 R 8H  substituent(s),
 
[5] a C 1-5  alkoxy group which may be substituted by 1-3 R 8E  substituent(s), and
 
[6] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by 1-3 R 8F , substituent(s),
 
Still more preferably
 
[1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B  described below,
 
Still even more preferably
 
[1] a 4- to 10-membered heterocycloalkyl group which may be substituted by at least one halogen atom, C 1-8  alkyl group, or an oxo.
 
     R 8A  is preferably 
     [8A-1] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-4 R 8A1  substituent(s),
 
[8A-2] a (C 1-5  alkyl) m8a -amino group (m8a: 0˜2) which may be substituted by 1-11 halogen atom(s), and
 
[8A-3] a hydroxy;
 
     R 8A  is more preferably 
     [8A-1] a 6-membered heterocycloalkyl group which may be substituted by 1-2 R 8A1  substituent(s),
 
[8A-2] a (C 1-3  alkyl) m8a -amino group (m8a: 0˜2) which may be substituted by 1-11 halogen atom(s), and
 
[8A-3] a hydroxy;
 
     R 8A1  is preferably 
     [8A1-1] a C 1-8  alkyl group,
 
[8A1-2] a C 1-8  alkylsulfonyl group,
 
[8A1-3] a (C 1-5  alkyl) m8b -aminosulfonyl group (m8b: 0˜2), or
 
[8A1-4] an oxo group,
 
more preferably
 
[8A1-1] a C 1-3  alkyl group,
 
[8A1-2] a C 1-3  alkylsulfonyl group, or
 
[8A1-3] a (C 1-3  alkyl) m8b -aminosulfonyl group (m8b: 0),
 
     R 8B  is preferably 
     [8B-1] a C 1-6  alkyl group which may be substituted by 1-13 R 8B1  substituent(s),
 
[8B-2] a C 2-6  alkynyl group,
 
[8B-3] a C 3-6  cycloalkyl group which may be substituted by [1] cyano(s) or [2] C 1-6  alkyl group(s),
 
[8B-4] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-10 R 8B2  substituent(s),
 
[8B-5] a C 1-6  alkoxy group which may be substituted by 1-5 substituent(s) selected from the group consisting of [1] a C 1-5  alkoxy group and [2] a C 3-6  cycloalkyl group,
 
[8B-6] a C 1-5  alkoxycarbonyl group,
 
[8B-7] a C 1-5  alkylsulfonyl group,
 
[8B-8] a 5- to 6-membered heteroarylsulfonyl group,
 
[8B-9] a cyano,
 
[8B-10] a C 1-6  alkanoyl group which may be substituted by 1-2 R 8B3  substituent(s),
 
[8B-11] a C 3-8  cycloalkylcarbonyl group,
 
[8B-12] a (C 1-5  alkyl) m8c -aminosulfonyl group (m8c: 0˜2),
 
[8B-13] a C 1-6  alkylsulfonyl (C 0-6  alkyl) amino group,
 
[8B-14] a (C 1-8  alkyl) m8d -amino group (m8d: 0˜2) which may be substituted by 1-3 R 8B4  substituent(s),
 
[8B-15] a hydroxy,
 
[8B-16] a (C 1-6  alkyl) m8e -aminocarbonyl group (m8e: 0˜2), or
 
[8B-17] a C 1-4  alkoxycarbonylamino group
 
more preferably
 
[8B-1] a C 1-5  alkyl group which may be substituted by 1-3 R 8B1 ,
 
[8B-2] a C 2-5  alkynyl group,
 
[8B-3] a C 3-5  cycloalkyl group which may be substituted by [1] a cyano or [2] a C 1-6  alkyl group,
 
[8B-4] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-8 R 8B2  substituent(s),
 
[8B-5] a C 1-5  alkoxy group which may be substituted by 1-2 substituent(s) selected from the group consisting of [1] a C 1-3  alkoxy group and [2] a C 3-6  cycloalkyl group,
 
[8B-6] a C 1-3  alkylsulfonyl group,
 
[8B-7] a cyano,
 
[8B-8] a C 1-6  alkanoyl group which may be substituted by a R 8B3  substituent,
 
[8B-9] a C 3-5  cycloalkylcarbonyl group,
 
[8B-10] a (C 1-3  alkyl) m8c -aminosulfonyl group (m8c:1-2),
 
[8B-11] a C 1-3  alkylsulfonyl (C 0-3  alkyl) amino group,
 
[8B-12] a (C 1-5  alkyl) m8a -amino group (m8d:0-1) which may be substituted by 1-2 R 8B4  substituent(s),
 
[8B-13] a hydroxy, or
 
[8B-14] a (C 1-3  alkyl) m8e -aminocarbonyl group (m8e:0-1).
 
     R 8B1  is preferably 
     [8B1-1] a C 3-6  cycloalkyl group,
 
[8B1-2] a hydroxy,
 
[8B1-3] a C 1-8  alkoxy group which may be substituted by 1-2 C 1-5  alkoxy group(s), or
 
[8B1-4] a cyano,
 
More preferably
 
[8B1-1] a C 3-5  cycloalkyl group,
 
[8B1-2] a hydroxy,
 
[8B1-3] a C 1-8  alkoxy group which may be substituted by 1 C 1-3  alkoxy group, or
 
[8B1-4] a cyano,
 
     R 8B2  is preferably 
     [8B2-1] a halogen atom,
 
[8B2-2] a C 1-6  alkyl group,
 
[8B2-3] an oxo,
 
[8B2-4] a hydroxy, or
 
[8B2-5] a deuterium atom,
 
more preferably
 
[8B2-1] a fluorine atom,
 
[8B2-2] a C 1-3  alkyl group,
 
[8B2-3] an oxo, or
 
[8B2-4] a hydroxyl.
 
     R 8B3  is preferably 
     [8B3-1] a (C 1-6  alkyl) m8f -amino group (m8f: 0˜2),
 
more preferably
 
[8B3-1] a (C 1-3  alkyl) m8f -amino group (m8f: 2).
 
     R 8B4  is preferably 
     [8B4-1] a C 3-6  cycloalkyl group, or
 
[8B4-2] a hydroxy;
 
     R 8C  is preferably 
     [8C-1] a hydroxyl,
 
[8C-2] a (C 1-3  alkyl) m8h -amino group (m8h:0-1) which may be substituted by a (C 1-3  alkyl) m8i -aminosulfonyl group (m8i: 0˜2),
 
[8C-3] a C 1-3  alkylsulfonyl group,
 
     R 8D  is preferably 
     [8D-1] a C 1-6  alkyl group which may be substituted by a R 8D1  substituent,
 
[8D-2] a hydroxy group,
 
[8D-3] a C 1-3  alkylsulfonyl group, or
 
[8D-4] a C 1-4  alkoxycarbonyl group;
 
     R 8D1  is preferably 
     [8D1-1] a hydroxy group, or
 
[8D1-2] a C 1-3  alkoxy group;
 
     R 8H  is preferably 
     [8H-1] a 4- to 6-membered heterocycloalkyl group, 
     R 8E  is preferably 
     [8E-1] a hydroxy group,
 
[8E-2] a C 1-8  alkoxy group which may be substituted by 1-2 R 8E7  substituent(s),
 
[8E-3] a C 1-3  alkylsulfonyl group,
 
[8E-4] a C 1-4  alkoxycarbonyl group,
 
[8E-5] a 4- to 6-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by 1-2 R 8E1  substituent(s),
 
[8E-6] a (C 1-5  alkyl) m8k1 -amino group (m8k1: 0˜2) which may be substituted by a R 8E2  substituent,
 
[8E-7] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-4 R 8E3  substituent(s),
 
[8E-8] a 5- to 6-membered heteroaryl group,
 
[8E-9] a (C 1-6  alkyl) m8k2 -aminocarbonyl group (m8k2: 0˜2) which may be substituted by 1-2 R 8E6  substituent(s),
 
[8E-10] a C 1-5  alkoxy group which may be substituted by a R 8E7  substituent,
 
[8E-11] a C 1-3  alkylthio group,
 
[8E-12] a C 1-3  alkylsulfinyl group,
 
[8E-13] a C 1-5  alkylsulfonyl group,
 
[8E-14] a C 1-3  alkylsulfonyl (C 0-8  alkyl) amino group,
 
[8E-15] a 4- to 6-membered heterocycloalkylsulfonyl (C 0-3  alkyl) amino group which may be substituted by 1-3 C 1-8  alkyl group(s);
 
more preferably
 
[8E-1] a (C 1-3  alkyl) m8k1 -amino group (m8k1: 2) which may be substituted by one or more R 8E2 ,
 
[8E-2] a C 1-8  alkoxy group which may be substituted by one or more R 8E7  
 
[8E-3] a C 1-3  alkylsulfonyl group,
 
[8E-4] a (C 1-5  alkyl) m8k1 -amino group (m8k1: 0˜2) which may be substituted by a R 8E2  substituent,
 
[8E-5] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-4 R 8E3  substituent(s),
 
[8E-6] a 4- to 6-membered heterocycloalkylsulfonylamino group which may be substituted by 1-2 C 1-3  alkyl group(s);
 
     R 8E1  is preferably 
     [8E1-1] a C 1-4  alkoxycarbonyl group,
 
[8E1-2] a C 1-3  alkanoyl group,
 
[8E1-3] a C 1-5  alkylsulfonyl group,
 
[8E1-4] a (C 1-3  alkyl) m8k3 -aminosulfonyl group (m8k3: 0-2),
 
[8E1-5] a 4- to 6-membered heterocycloalkyl group;
 
     R 8E2  is preferably 
     [8E2-1] a hydroxy group,
 
[8E2-2] a C 1-6  alkoxycarbonyl group,
 
[8E2-3] a C 3-6  cycloalkyl group which may be substituted by a C 1-8  alkyl group which may be substituted by a hydroxy,
 
[8E1-4] a C 1-5  alkanoyl group which may be substituted by 1-3 substituent(s) selected from the group consisting of [1] a (C 1-3  alkyl) m8k4 -amino group (m8k4: 0˜2) and [2] a halogen atom,
 
[8E2-5] a (C 1-3  alkyl) m8k5 -aminocarbonyl group (m8k5: 0-2),
 
[8E2-6] a C 1-3  alkylsulfonyl group,
 
[8E2-7] a (C 1-3  alkyl) m8k6 -aminosulfonyl group (m8k6: 0-1) which may be substituted by a C 1-4  alkoxycarbonyl group.
 
more preferably
 
[8E2-1] a hydroxy group.
 
     R 8E3  is preferably 
     [8E3-1] a C 1-6  alkyl group which may be substituted by 1-3 substituent(s) selected from the group consisting of [1] a hydroxy group or [2] a C 1-3  alkylcarbonyloxy group,
 
[8E3-2] a C 1-4  alkylcarbonyloxy group,
 
[8E3-3] a hydroxy group,
 
[8E3-4] a C 3-5  cycloalkyl group,
 
[8E3-5] a C 1-4  alkoxycarbonyl group,
 
[8E3-6] a C 1-5  alkylsulfonyl group,
 
[8E3-7] a (C 1-3  alkyl) m8k8 -aminocarbonyl group (m8k8: 0-2),
 
[8E3-8] a C 1-3  alkanoyl group which may be substituted by a hydroxy,
 
[8E3-9] an oxo group, or
 
[8E3-10] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-3 substituent(s) selected from the group consisting of [1] a C 1-3  alkanoyl group, [2] a C 1-4  alkoxycarbonyl group, or [3] a C 1-3  alkylsulfonyl group;
 
more preferably
 
[8E3-1] a (C 1-3  alkyl) m8k8 -aminocarbonyl group (m8k8: 0-2), or
 
[8E3-2] an oxo group;
 
     R 8E4  is preferably 
     [8E4-1] a 4- to 6-membered heterocycloalkyl group,
 
[8E4-2] a C 1-3  alkanoyl group,
 
[8E4-3] a C 1-3  alkoxycarbonyl group,
 
[8E4-4] a C 1-3  alkylsulfonyl group,
 
[8E4-5] a C 1-3  alkylaminosulfonyl group;
 
     R 8E6  is preferably 
     [8E6-1] a C 2-3  alkenylcarbonyloxy group,
 
[8E6-2] a hydroxy group,
 
[8E6-3] a cyano,
 
[8E6-4] a (C 1-3  alkyl)m8k9-amino group (m8k9: 0˜2) which may be substituted by 1-2 hydroxy group(s),
 
[8E6-5] a C 1-3  alkoxy group which may be substituted by a hydroxy,
 
[8E6-6] a C 1-4  alkylcarbonyloxy group,
 
[8E6-7] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-3 C 1-8  alkyl group(s),
 
[8E6-8] a 5- to 6-membered heteroaryl group;
 
     R 8E7  is preferably 
     [8E7-1] a hydroxy group,
 
[8E7-2] a C 1-3  alkoxy group which may be substituted by a hydroxy;
 
     R 8F  is preferably 
     [8F-1] a C 1-8  alkyl group which may be substituted by 1-3 R 8F1  substituent(s),
 
[8F-2] a C 3-6  cycloalkyl group,
 
[8F-3] a C 1-3  alkanoyl group which may be substituted by 1-7 halogen atom(s),
 
[8F-4] a C 1-5  alkylcarbonyloxy group,
 
[8F-5] a C 1-5  alkoxycarbonyl group,
 
[8F-6] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-3 R 8F2 , substituent(s),
 
[8F-7] a C 1-5  alkylsulfonyl group, or
 
[8F-8] a hydroxy group;
 
More preferably
 
[8F-1] a C 1-3  alkyl group which may be substituted by a R 8F1  substituent,]
 
[8F-2] a C 3-5  cycloalkyl group,
 
[8F-3] a 4- to 6-membered heterocycloalkyl group which may be substituted by a R 8F2  substituent,
 
[8F-4] a C 1-3  alkylsulfonyl group,
 
     R 8F1  is preferably 
     [8F1-1] a hydroxy group,
 
[8F1-2] a C 1-5  alkoxy group, or
 
[8F1-3] a halogen atom;
 
     R 8F2  is preferably 
     [8F2-1] a 4- to 6-membered heterocycloalkyl group,
 
[8F2-2] a C 1-5  alkoxycarbonyl group, or
 
[8F2-3] a C 1-3  alkylsulfonyl group,
 
     R 8G  is preferably 
     [8G-1] a hydroxycarbonyl group,
 
[8G-2] a hydroxy group, or
 
[8G-3] a (C 1-5  alkyl)m813-amino group (m813: 0-2),
 
     R 9  is preferably 
     [1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by 1-8 R 9A  substituent(s),
 
[3] a C2-6 alkenyl group,
 
[4] a C 2-8  alkynyl group which may be substituted by 1-6 R 9C  substituent(s),
 
[5] a C 3-6  cycloalkyl group,
 
[6] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-5 R 9D  substituent(s),
 
[7] a C 6  aryl group which may be substituted by 1-2 R 9E  substituent(s),
 
[8] a 5- to 6-membered heteroaryl group which may be substituted by 1-3 C 1-5  alkyl group(s),
 
[9] a cyano,
 
[10] a C 1-6  alkanoyl group,
 
[11] a 4- to 6-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by a C 1-5  alkyl group,
 
[12] a halogen atom,
 
[13] a (C 1-4  alkyl) m9c -amino group (m9c: 0˜2) which may be substituted by a R 9F  substituent,
 
[14] a hydroxy,
 
[15] a C 1-6  alkoxy group which may be substituted by 1-5 R 9G  substituent(s),
 
[16] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by one or two 4- to 6-membered heterocycloalkyl group(s),
 
[17] a C 1-5  alkylthio group which may be substituted by (C 1-3  alkyl) m9f -amino group(s) (m9f: 0˜2),
 
[18] a C 1-5  alkylsulfonyl group which may be substituted by (C 1-3  alkyl) m9g -amino group(s) (m9g: 0˜2),
 
[19] a (C 1-3  alkyl) m9h -aminosulfonyl group (m9h: 0˜2),
 
[20] a 4- to 6-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by a C 1-3  alkyl group;
 
More preferably
 
[1] a hydrogen atom,
 
[2] a C 1-6  alkyl group which may be substituted by a R 9A  substituent,
 
[3] a C 2-5  alkenyl group,
 
[4] a C 2-8  alkynyl group which may be substituted by a R 9C  substituent,
 
[5] a C 3-6  cycloalkyl group,
 
[6] a 4- to 6-membered heterocycloalkyl group which may be substituted by a R 9D  substituent,
 
[7] a 5- to 6-membered heteroaryl group which may be substituted by a C 1-5  alkyl group,
 
[8] a cyano,
 
[9] a C 1-3  alkanoyl group,
 
[10] a halogen atom,
 
[11] a (C 1-4  alkyl) m9b -n amino group (m9b: 0),
 
[12] a hydroxy,
 
[13] a C 1-6  alkoxy group which may be substituted by 1-3 R 9G  substituent(s),
 
[14] a 4- to 6-membered heterocycloalkyloxy group which may be substituted by a 4- to 6-membered heterocycloalkyl group,
 
Even more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by one or more R 9A  substituent(s),
 
[3] a C 2-8  alkenyl group which may be substituted by one or more R 9B  substituent(s),
 
[4] a C 2-8  alkynyl group which may be substituted by one or more R 9C  substituent(s),
 
[5] a C 3-8  cycloalkyl group,
 
[6] a halogen atom,
 
Still more preferably
 
[1] a hydrogen atom,
 
[2] a C 1-8  alkyl group which may be substituted by one or more R 9A  substituent(s),
 
[3] a C 2-8  alkynyl group which may be substituted by one or more R 9C  substituent(s).
 
     R 9A  is preferably 
     [9A-1] a C 3-6  cycloalkyl group,
 
[9A-2] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-3 R 9A1  substituent(s),
 
[9A-3] a hydroxy group, or
 
[9A-4] a C 1-6  alkoxy group,
 
More preferably
 
[9A-1] a 4- to 6-membered heterocycloalkyl group which may be substituted by a R 9A1  substituent,
 
[9A-2] a hydroxy group, or
 
[9A-3] a C 1-3  alkoxy group,
 
     R 9A1  is preferably 
     [9A1-1] a C 1-5  alkyl group,
 
[9A1-2] a C 3-5  cycloalkyl group, or
 
[9A1-3] a 4- to 6-membered heterocycloalkyl group,
 
More preferably
 
[9A1-1] a C 1-3  alkyl group,
 
[9A1-2] a C 3  cycloalkyl group, or
 
[9A1-3] a 4-membered heterocycloalkyl group,
 
     R 9C  is preferably 
     [9C-1] a C 1-8  alkoxy group,
 
[9C-2] a (C 1-5  alkyl) m9b -amino group (m9b: 0˜2) which may be substituted by 1-2 C 6  aryl group(s),
 
[9C-3] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-3 R 9C1  substituent(s),
 
[9C-4] a C 3-6  cycloalkyl group,
 
[9C-5] a hydroxy group, or
 
[9C-6] a hydroxycarbonyl group;
 
More preferably
 
[9C-1] a C 1-5  alkoxy group,
 
[9C-2] a (C 1-3  alkyl) m9b -amino group (m9b: 2) which may be substituted by 1-2 C 6  aryl group(s),
 
[9C-3] a 4- to 6-membered heterocycloalkyl group which may be substituted by 1-2 R 9C1  substituent(s),
 
[9C-4] a C 3-5  cycloalkyl group,
 
[9C-5] a hydroxy group.
 
     R 9C1  is preferably 
     [9C1-1] a C 3-5  cycloalkyl group,
 
[9C1-2] a 4- to 6-membered heterocycloalkyl group, or
 
[9C1-3] an oxo group,
 
More preferably
 
[9C1-1] a C 3  cycloalkyl group,
 
[9C1-2] a 4- to 6-membered heterocycloalkyl group, or
 
[9C1-3] an oxo group,
 
     R 9D  is preferably 
     [9D-1] a C 1-5  alkyl group which may be substituted by one or two 4- to 6-membered heterocycloalkyl group(s),
 
[9D-2] a C 3-5  cycloalkyl group,
 
[9D-3] a 4- to 6-membered heterocycloalkyl group, or
 
[9D-4] a C 1-3  alkylsulfonyl group;
 
More preferably
 
[9D-1] a C 1-5  alkyl group which may be substituted by a 4- to 6-membered heterocycloalkyl group,
 
[9D-2] a 4- to 6-membered heterocycloalkyl group, or
 
[9D-3] a methylsulfonyl group;
 
     R 9E  is preferably 
     [9E-1] a halogen atom,
 
[9E-2] a hydroxy group,
 
[9E-3] a hydroxycarbonyl group, or
 
[9E-4] a C 1-3  alkyl group which may be substituted by a hydroxy;
 
     R 9F  is preferably 
     [9F-1] a C 1-3  alkylsulfonyl group,
 
[9F-2] a (C 1-3  alkyl) m9f1 -aminosulfonyl group (m9f1: 0˜2), or
 
[9F-3] a C 1-3  alkanoyl group which may be substituted by (C 1-3  alkyl) m9f2 -amino group(s) (m9f2: 0-2),
 
     R 9G  is preferably 
     [9G-1] a hydroxy group,
 
[9G-2] a hydroxycarbonyl group,
 
[9G-3] a C 6  aryl group which may be substituted by C 1-3  alkoxy group(s),
 
[9G-4] a (C 1-3  alkyl) m9g1 -amino group (m9g1: 0˜2),
 
[9G-5] a C 1-5  alkoxy group which may be substituted by 1-3 R 9G1  substituent(s), or
 
[9G-6] a 5- to 6-membered heteroaryl group;
 
More preferably
 
[9G-1] a hydroxy group,
 
[9G-2] a (C 1-3  alkyl) m9g1 -amino group (m9g1: 0˜2),
 
[9G-3] a C 1-3  alkoxy group which may be substituted by a R 9G1  substituent, or
 
[9G-4] a 5- to 6-membered heteroaryl group;
 
     R 9G1  is preferably 
     [9G1-1] a C 1-3  alkoxy group, or
 
[9G1-2] a hydroxycarbonyl group.
 
     Preferably, A 5  is NH, while the remaining are C, R 3  is a cyano group, R 6  and R 6′  are methyl, R 8  is (1) a hydrogen atom, (2) a C 1-8  alkyl group which may be substituted by one or more R 8A , (3) a C 2-8  alkenyl group, (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B , (5) a 5- to 14-membered heteroaryl group which may be substituted by a C 1-8  alkyl group, (6) a (C 1-8  alkyl) m8g -aminocarbonyl group which may be substituted by one or more R 8C , (7) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R 8D , (8) a hydroxycarbonyl group, (9) a C 0-8  alkoxy (C 0-8  alkyl) aminocarbonyl group which may be substituted by one or more hydroxy group(s), (10) a halogen atom, (11) a hydroxy group, (12) a C 1-8  alkoxy group which may be substituted by one or more R E , (13) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R 8F , (14) an aminosulfonyloxy group which may be substituted by one or more C 1-8  alkyl group(s), (15) a C 1-8  alkyl thio group which may be substituted by a (C 1-8  alkyl)n-amino group, or (16) a C 1-8  alkylsulfonyl group which may be substituted by R 8G , R 9  is (1) a hydrogen atom, (2) a C 1-8  alkyl group which may be substituted by one or more R 9A , (3) a C 2-8  alkenyl group which may be substituted by one or more R 9B , (4) a C 2-8  alkynyl group which may be substituted by one or more R 9C , (5) a C 3-8  cycloalkyl group, (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 9D , (7) a C 6-10  aryl group which may be substituted by one or more R 9E , (8) a 5- to 14-membered heteroaryl group which may be substituted by a C 1-8  alkyl group, (9) a cyano group, (10) a C 1-8  alkanoyl group, (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by a C 1-8  alkyl group, (12) a halogen atom, (13) a (C 1-8  alkyl) m9c -amino group which may be substituted by one or more R 9F , (14) a C 1-8  alkylsulfonylamino group, (15) a nitro group, (16) a hydroxy group, (17) a C 1-8  alkoxy group which may be substituted by one or more R 9G , (18) a C 1-8  alkyl thio group which may be substituted by a (C 1-8  alkyl) m9f -amino group, (19) a C 1-8  alkylsulfonyl group which may be substituted by a (C 1-8  alkyl) m9g -amino group, (20) a (C 1-8  alkyl) m9h -aminosulfonyl group, or (21) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by a C 1-8  alkyl group, and R 1 , R 2 , R 5 , R 7  and R 10  are defined above. 
     More preferably, A 5  is NH while the remaining are C, R 3  is a cyano group, R 6  and R 6′  are methyl groups, R 8  is (1) a hydrogen atom, (2) a C 1-8  alkyl group which may be substituted by one or more R 8A , (3) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R 8B , or (4) a C 1-8  alkoxy group which may be substituted by one or more R 8E , R 9  is (1) a hydrogen atom, (2) a C 1-8  alkyl group which may be substituted by one or more R 9A , (3) a C 2-8  alkynyl group which may be substituted by one or more R 9C , (4) a C 3-8  cycloalkyl group, or (5) a halogen atom, and R 1 , R 2 , R 5 , R 7  and R 10  are an hydrogen atom. 
     According to the present invention, examples of the salts of the compounds that are represented by the Formula (I) include hydrochloric acid salt, hydrobromic acid salt, hydriodic acid salt, phosphoric acid salt, phosphonic acid salt, sulfuric acid salt, sulfonic acid salt such as methanesulfonic acid salt, p-toluene sulfonic acid salt and the like, carboxylic acid salt such as acetic acid salt, citric acid salt, malic acid salt, tartaric acid salt, succinic acid salt, salicylic acid salt and the like, or alkali metal salt such as sodium salt, potassium salt and the like, alkaline earth metal salt such as magnesium salt, calcium salt and the like, ammonium salt such as ammonium salt, alkyl ammonium salt, dialkyl ammonium salt and trialkyl ammonium salt tetraalkyl ammonium salt. Preferably, the salts are pharmaceutically acceptable salts. These salts are produced by brining the compounds described above in contact with an acid or a base which can be used for the production of a pharmaceutical product. 
     According to the present invention, the compounds that are represented by the Formula (I) or salts thereof can be an anhydride or a solvate such as a hydrate and the like. Herein, the term “solvate (d)” indicates a phenomenon by which solute molecules or ions contained in a solution strongly attract neighboring solvent molecules to form a huge group of molecules. When the solvent is water, it is called “hydrate (d).” The solvate can be any one of a hydrate and a non-hydrate. Preferably, the solvates are pharmaceutically acceptable solvates. For the non-hydrate, alcohol (for example, methanol, ethanol, n-propanol), dimethylformamide and the like can be used. 
     The compounds of the present invention and salts thereof may be present in several tautomer forms, for example, enol and imine form, keto and enamine form, and a mixture thereof. In a solution, a tautomer is present as a mixture of tautomeric set. In case of solid form, one type of tautomer is generally present in dominant ratio. In this regard, even if only one type of tautomer is described, the present invention includes all types of tautomer of the compounds of the present invention. 
     The present invention includes all types of stereoisomer of the compounds of the present invention that are represented by the Formula (I) (for example, enantiomer, diastereomer (including cis and trans geometric isomer)), racemate of the isomer and a mixture thereof. For example, the compounds having the Formula (I) of the present invention may have one or more asymmetric center, and the present invention includes a racemic mixture, a diastereomer mixture and enantiomer of such compound. 
     When the compounds of the present invention are obtained in free form, they can be converted into a salt, a hydrate or solvate thereof which can be formed from the compounds according to a method generally known in the art. 
     Further, when the compounds of the present invention are obtained in the form of a salt, hydrate or solvate of the compounds, they can be converted to free form according to a method generally known in the art. 
     The present invention include all isotopes of compounds that are represented by the Formula (I). The isotopes of the compounds of the present invention indicate the compounds of the present invention in which at least one atom is substituted by an atom with the same atomic number (i.e., number of protons) but with different mass number (sum of the number of protons and the number of neutrons). Example of the isotopes that are included in the compounds of the present invention includes a hydrogen atom, a carbon atom, a nitrogen atom, an oxygen atom, a phosphorus atom, a sulfur atom, a fluorine atom, a chlorine atom and the like, and  2 H,  3 H,  13 C,  14 C,  15 N,  17 O,  18 O,  31 P,  32 P,  35 S,  18 F,  36 Cl and the like are included. In particular, a radioisotope which decays by emitting radiation, for example  3 H and  14 C, are useful for determining the distribution of a pharmaceutical agent or a compound in a living tissue, etc. On the other hand, a stable isotope does not degrade and remains in almost the same amount without exhibiting radioactivity, and therefore can be safely used. Isotopes of the compounds of the present invention can be converted by replacing a chemical reagent used for synthesis with a chemical reagent comprising a corresponding radioisotope according to a method generally known in the art. 
     Further, the compounds (I) of the present invention can be administered in the form of prodrug. Herein, the term “prodrug” indicates the derivatives of the compounds having the Formula (I) that can be converted to the compounds having the Formula (I) or salts or solvates thereof after administration by enzymatic or non-enzymatic degradation under a physiological condition. The prodrug can be in inactive form when it is administered to a patient. However, in organisms, it converts to the compounds having the Formula (I) and present therein in the active form. 
     For example, the prodrug converts into desired drug form at specific pH or by an enzymatic action. Conventional prodrug is a compound having a hydrolyzable ester residue which produces a free acid in organisms. Examples of such hydrolyzable ester residue include a residue having a carboxyl moiety of which free hydrogen (for example, a free hydrogen in a carboxyl group when Y in the Formula (I) has a carboxyl group) is replaced by a C 1-4  alkyl group, a C 2-7  alkanoyloxymethyl group, a 1-(alkanoyloxy)ethyl group having 4 to 9 carbon atoms, a 1-methyl-1-(alkanoyloxy)-ethyl group having 5 to 10 carbon atoms, an alkoxycarbonyloxymethyl group having 3 to 5 carbon atoms, a 1-(alkoxycarbonyloxy)ethyl group having 4 to 7 carbon atoms, a 1-methyl-1-(alkoxycarbonyloxy)ethyl group having 5 to 8 carbon atoms, a N-(alkoxycarbonyl)aminomethyl having 3 to 9 carbon atoms, a 1-(N-(alkoxycarbonyl)amino)ethyl group having 4 to 10 carbon atoms, a 3-phthalidyl group, a 4-crotonolactonyl group, a γ-butyrolacton-4-yl group, a di-N,N—(C 1-2 )alkylamino(C 2-3 )alkyl group (for example, N,N-dimethylaminoethyl group), a carbamoyl(C 1-2 )alkyl group, a N,N-di(C 1-2 )alkylcarbamoyl-(C 1-2 )alkyl group, a piperidino(C 2-3 )alkyl group, a pyrrolidino(C 2-3 )alkyl group, or a morpholino(C 2-3 ) alkyl group, but not limited thereto. 
     Representative Preparation Method 
     The compounds having the Formula (I) of the present invention can be produced by the method described below, for example. However, method of preparing the compounds of the present invention is not limited thereto. Further, depending on necessity, order of the reaction step like introduction of a substituent group, etc. can be changed. Although the compounds of the present invention are novel compounds which have not been described in literatures, they can be prepared according to a chemical method that is generally known in the art. Still further, as for the reacting compounds that are used for the preparation, commercially available ones can be used or they can be produced according to a method that is generally known in the art depending on necessity. 
     In the following reaction schemes showing the reaction step, A 1  to A 10  and R 1  to R 10  are as defined in the Formula (I). PR 1  to PR 10  are the same as R 1  to R 10  that are defined in the Formula (I) or represent a group which can be converted to R 1  to R 10  according to modification or deprotection of a functional group. 
     Other abbreviated symbols described in the following reaction schemes have the general meanings that can be understood by a skilled person in the art. 
     PG represents a protecting group (for example, methyl, ethyl, t-butyl, benzyl, substituted benzyl, acetyl, t-butoxycarbonyl, benzyloxycarbonyl, methanesulfonyl, trifluoromethanesulfonyl, trimethylsilyl, triethylsilyl, triisopropylsilyl, t-butyldimethylsilyl, tetrahydropyranyl and the like). In the preparation method described below, when a defined group is subjected to undesirable chemical modification under a condition for implementing the method, the preparation can be carried out by using means such as protection and deprotection of a functional group, etc. 
     Herein, regarding selection, addition and removal of a protecting group include the methods described in “Protective Groups in Organic Synthesis” (Greene and Wuts, 4 th  edition, John Wiley &amp; Sons 2007), and they can be suitably employed according to each reaction condition. 
     LG represents a leaving group such as fluorine, chlorine, bromine, iodine, methanesulfonate, trifluoromethanesulfonate and the like, which can be applied for the reaction described above. 
     In addition, abbreviated symbols that are typically used to describe the general synthetic method and examples below and names of the chemical reagents and solvents corresponding to the chemical formulae are listed in the following. 
     9-BBN 9-borabicyclo[3.3.1]nonane 
     AcOH acetic acid 
     BINAP 2,2′-bis (diphenylphosphino)-1,1′-binaphthyl 
     BF 3 OEt 2  trifluoroboron etherate 
     t-BuOK potassium t-butoxy 
     n-BuLi n-butyl lithium 
     t-BuONa sodium t-butoxy 
     CDI carbonyl diimidazole 
     CPME c-pentylmethyl ether 
     DBU 1,8-diazabicyclo[5.4.0]-7-undecene 
     DCM dichloromethane 
     DEAD diethyl azodicarboxylate 
     DDQ 2,3-dichloro-5,6-dicyano-p-benzoquinone 
     DIPEA N,N-diisopropylethylamine 
     DMA N,N-dimethylacetamide 
     DME dimethoxyethane 
     DMF N,N-dimethyl formamide 
     DMSO dimethyl sulfoxide 
     DPPF bis (diphenylphosphino)ferrocene 
     EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride 
     EtOAc ethyl acetate 
     HOBt 1-hydroxybenzotriazole 
     KHMDS potassium hexamethyldisilazide 
     LDA lithium diisopropylamide 
     LiHMDS lithium hexamethyldisilazide 
     MeCN acetonitrile 
     Mel methyl iodide 
     MeOH methanol 
     MTBE t-butylmethyl ether 
     NaHMDS sodium hexamethyldisilazide 
     NMP N-methylpyrrolidone 
     Pd 2 (dba) 3  tris (dibenzylideneacetone) dipalladium (0) 
     Pd(OAc) 2  palladium acetate 
     PdCl 2 (CH 3 CN) 2  dichloro(bisacetonitrile) palladium (II) 
     PdCl 2 (PPh 3 ) 2  dichlorobis (triphenylphosphine) palladium (II) 
     Pd(PPh 3 ) 4  tetrakis (triphenylphosphine) palladium (0) 
     P(t-Bu) 3  tri t-butylphosphine 
     PPh 3  triphenylphosphine 
     P(o-tol) 3  tri o-tolylphosphine 
     TEA triethylamine 
     TEMPO 2,2,6,6-tetramethylpiperidin-1-oxyl 
     TFA trifluoroacetic acid 
     TFAA trifluoroacetic anhydride 
     TFE trifluoroethanol 
     THF tetrahydrofuran 
     TMAD 1,1′-azobis (N,N-dimethylformamide) 
     TMSCl trimethylsilyl chloride 
     TMSI trimethylsilyl iodide 
     DavePhos 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl 
     JohnPhos 2-(di-t-butylphosphino)biphenyl 
     c-Hexyl JohnPhos 2-(dicyclohexylphosphino)biphenyl 
     S-Phos 2′,6′-dimethoxy-2-(dicyclohexylphosphino)biphenyl 
     X-Phos 2′,4′,6′-triisopropyl-2-(dicyclohexylphosphino)biphenyl 
     t-ButylX-Phos 2′,4′,6′-triisopropyl-2-(di-t-butylphosphino)biphenyl 
     Xantphos 4,5′-bis (diphenylphosphino)-9,9′-dimethylxanthene 
     Preparation Method I 
     This is one of the methods for producing the compounds of the Formula (I) in which A 5  is N and R 5  is H. 
     
       
         
         
             
             
         
       
     
     Step I-1 
     It is an alkylation step of a cyclic ketone derivative Ia. The step can be carried out by reacting cyclic ketone derivative Ia with an alkylating agent corresponding to R 6  and R 6′  in the presence of a base. For example, it can be carried out in view of the method described in Journal of the American Chemical Society, 115 (23), 10628-36; 1993 and Organic Letters, 9 (24), 5027-5029; 2007, etc. The reaction is carried out in a solvent under the condition of a reaction temperature of −20° C. to boiling point of the solvent, in the presence or the absence of a catalyst. When R 6  and R 6′  are atomic groups other than a hydrogen atom, the reaction order can be optionally selected, and separation and purification can be carried out at each step or the reaction can be carried out continuously. 
     As for the alkylating agent, examples thereof include an alkyl halide such as Mel, ethyl iodide, 2-iodopropane, 1,4-dibromobutane, 1,1′-oxybis (2-bromoethane) and the like, dimethyl sulfate, and sulfonic acid ester such as methylmethanesulfonate, methyl tosylate and methyltrifluoromethanesulfonate. Preferably, it is an alkyl halide such as Mel and the like. As for the catalyst, examples thereof include a phase transfer catalyst such as tetrabutylammonium chloride and tetrabutylammonium hydrogen sulfate. Preferably, it is tetrabutylammonium hydrogen sulfate. As for the base, examples thereof include an inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, calcium hydride and the like or an organic base such as t-BuOK, t-BuONa, pyridine, TEA, DIPEA, LDA, LiHMDS and n-BuLi. Preferably, it is potassium hydroxide, potassium t-butoxy, or sodium t-butoxy. As for the solvent, examples thereof include toluene, xylene, n-hexane, cyclohexane, DMF, DMA, EtOAc, DMSO, dichloromethane, carbon tetrachloride, THF, dioxane, acetonitrile, water, methanol, ethanol and a mixture thereof. Preferably, it is a mixture solvent of water-THF or THF. 
     Step I-2 
     It is the synthesis of carbazole skeleton Id according to Fischer method. This step is generally carried out by using cyclic ketone Ib in the presence of hydrazine compound Ic and an acid in a solvent or by using an acid as a solvent under the condition of a reaction temperature of 0° C. to boiling point of the solvent, and also can be carried out in view of the method described in Journal of Heterocyclic Chemistry, 28 (2), 321-3; 1991 and Bioorganic &amp; Medicinal Chemistry Letters (2008), 18 (24), 6479-6481. Further, when the reaction proceeds slowly, a zinc chloride catalyst and the like can be also used in view of the reaction condition disclosed in Organic Letters (2006), 8 (3), 367-370. The reaction consists of a step of producing phenyl hydrazone and a step of sigmatropic rearrangement. Separation and purification can be carried out at each step or the reaction can be carried out continuously. Further, according to the structure of aryl hydrazine, which is a reacting material of this reaction step, mixture of a position isomer can be obtained as a reaction product. Such position isomer can be separated from each other or used as a mixture for the next reaction step. 
     As for the acid used for the reaction, examples thereof include formic acid, acetic acid, methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, TFA, hydrochloric acid, sulfuric acid and pyridinium p-toluenesulfonate. Preferably, it is acetic acid, sulfuric acid, or TFA. As for the solvent, examples thereof include toluene, xylene, NMP, DMF, DMA, DMSO, sulfolane, dioxane, DME, TFE, diethylene glycol, triethylene glycol and a mixture thereof. 
     Step I-3 
     It is a step of oxidation at benzyl at 11-position of carbazole skeleton Id. This step is carried out by applying an oxidizing agent to a substrate in a solvent in the presence or absence of a catalyst under the condition of a reaction temperature of −20° C. to boiling point of the solvent. As for the reaction condition, the method described in Journal of Medicinal Chemistry, 51 (13), 3814-3824; 2008, etc. can be considered. 
     As for the oxidizing agent and the catalyst used for the reaction, DDQ, peracid such as, mCPBA and the like, cerium ammonium nitrate (IV) (CAN), permanganate such as potassium permanganate, barium permanganate and the like, sodium chlorite, hydrogen peroxide, or N-hydroxyphthalimide and the like can be used alone or in a combination thereof. Preferably, it is DDQ or N-hydroxyphthalimide. As for the reaction solvent used for the reaction, examples thereof include water, t-butanol, acetonitrile, THF, dichloromethane, ethyl acetate and a mixture thereof. Preferably, it is THF. 
     Preparation Method II 
     It is an exemplary method of producing β-ketoester intermediate IIg, which is used for constructing the skeleton of the compounds that are represented by the Formula (I). 
     
       
         
         
             
             
         
       
     
     Step II-1, Step II-2 
     It is an alkylation step at a position of carboxylic acid ester IIc or nitrile IIa. The step can be carried out by reacting with an alkylating agent corresponding to R 6  and R 6′  in a solvent under the condition of a reaction temperature of −20° C. to boiling point of the solvent, in the presence of a base. For example, it can be carried out in view of the method described in J. Org. Chem., 2007, 72 (25), 9541-9549 and European Journal of Organic Chemistry (21), 3449-3462, etc. The reagents and the condition for the reaction are the same as those described for Step I-1. 
     Step II-3 
     It is an ester hydrolysis step of carboxylic acid ester IId. This step can be carried out by hydrolysis in an aqueous solvent at the reaction temperature of 0° C. to boiling point of the solvent in the presence of an inorganic base, for example in view of the method described in Tetrahedron Lett. 3529, 1977. Alternatively, it can be carried out according to a method in which hydrolysis is carried out in the presence of an acid, in view of the method described in J. Am. Chem. Soc, 1977, 99, 2353, for example. As for the inorganic base, examples thereof include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and cesium carbonate. Preferably, it is sodium hydroxide or potassium hydroxide. As for the solvent, water, methanol, ethanol, tetrahydrofuran, dioxane, and the like can be used alone or in a combination thereof. Preferably, it is methanol comprising water or ethanol comprising water. As for the acid which can be used for acid hydrolysis, hydrochloric acid, sulfuric acid, trifluoroacetic acid and methanesulfonic acid can be used alone in a combination thereof. Preferably, it is sulfuric acid. 
     Step II-4, Step II-5 
     It is a direct (hetero)arylation step at a position of carboxylic acid ester or nitrile. This step can be carried out by S N Ar reaction in which carboxylic acid ester or nitrile is reacted with aromatic compound IIf having a leaving group in the presence of a base. It can be carried out in view of the method described in J. Am. Chem. Soc. 2000, 122, 712-713. Alternatively, it can be also carried out according to a method in which carboxylic acid ester or nitrile is reacted with aromatic compound IIf having a leaving group in the presence of a catalyst, a ligand and a base. For example, it can be carried out in view of the method described in Org. Lett, 2008, 10 (8), 1545, J. Org. Chem. 2003, 68, 8003 and Angew. Chem. Int. Ed. 2003, 42, 5051, etc. 
     As for the base used for the reaction, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, LiHMDS, NaHMDS, LDA, lithium dicyclohexylamide, lithium 2,2,6,6-tetramethyl pyrrolidide, KHMDS, t-BuONa, t-BuOK and the like can be used. Preferably, it is NaHMDS, KHMDS, or t-BuONa. As for the catalyst, ligand, or catalyst-ligand complex which are used for the reaction, palladium acetate, Pd 2 (dba) 3 , π-allyl palladium chloride dimer, PdCl 2 (CH 3 CN) 2 , trialkylproazaphosphatrane, {P(t-Bu) 3 PdBr} 2 , PPh 3 , P(o-tol) 3 , BINAP, DPPF, P(t-Bu) 3 , DavePhos, JohnPhos, c-Hexyl JohnPhos, S-Phos, X-Phos, t-ButylX-Phos, Xantphos, 4,5-bis[bis (3,5-bistrifluoromethylphenyl)phosphanyl]-9,9-dimethyl-9H-xanthene, 1,3-diallyldihydroimidazolium salt and the like can be used, for example. Preferably, it is triisobutylproazaphosphatrane. 
     Step II-6 
     It is a step of hydrolyzing nitrile IIb to carboxylic acid. This step can be carried out by hydrolysis in the presence of an acid under the condition of a reaction temperature of 0° C. to boiling point of the solvent, and the reaction conditions include that described in, for example, Tetrahedron, 64 (36), 8464-8475; 2008, etc. For the reaction, the acid itself can be used as a solvent or diluted with other solvent. Alternatively, it can be carried out by hydrolysis in the presence of an inorganic base under the condition of a reaction temperature of 0° C. to boiling point of the solvent, and the reaction condition described in, for example, Bioorganic &amp; Medicinal Chemistry Letters, 18 (2), 749-754; 2008, etc. can be employed. 
     The reaction consists of the hydrolysis of nitrile IIb to acid amide and further conversion into carboxylic acid. Separation and purification can be carried out at each step or the reaction can be carried out continuously. 
     As for the acid which is used for the reaction, examples thereof include methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, hydrochloric acid and sulfuric acid. As for the solvent, examples thereof include toluene, xylene, dioxane, dimethoxyethane, diethylene glycol, triethylene glycol, TFE and the like and a mixture thereof. As for the inorganic base, examples thereof include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and cesium carbonate. 
     Step II-7 
     It is a step of converting carboxylic acid IIe to β-ketoester. According to this step, the carboxylic acid as a reacting material is converted into an acid chloride, active ester and the like by an action of an activating agent in a solvent under the condition of a reaction temperature of 0° C. to boiling point of the solvent. Thereafter, the acid chloride or active ester is reacted with enolate of malonic acid monoester under the condition of a reaction temperature of 0° C. to boiling point of the solvent to give a target compound through decarboxylation. As for the reaction condition, a method described in J. Chem. Soc. Perkin Trans. 1 1988, 2345-2352 and Synthesis 1993, 290-292 can be used, for example. As for the method of activating carboxylic acid, examples thereof include a method of converting into an acid chloride by using thionyl chloride, oxalyl chloride, phosphorus oxychloride, etc. or a method of converting into an active ester by using CDI. Preferably, thionyl chloride or CDI is used. The activated carboxylic acid itself can be subjected to separation and purification, or can be used continuously for the next reaction. As for the method of producing an enolate of malonic acid monoester, a combination of magnesium salt like magnesium chloride, etc. and malonic acid monoester (and a salt thereof) or a Grignard reagent like i-propyl magnesium chloride, etc. and malonic acid monoester (and a salt thereof), etc. can be used. In order to improve the reaction yield, an organic base such as TEA, DIPEA and the like can be also added to the reaction system. As for the solvent, examples thereof include toluene, xylene, MeCN, THF, CPME, MTBE, NMP, DMF, DMA, DMSO, sulfolane, dioxane, DME, and the like and a mixture thereof. Preferably, it is MeCN, THF or DME. 
     Step II-8 
     It is a step of converting nitrile IIb to β-ketoester. This step can be carried out by so-called Blaise reaction in which 2-halo carboxylic acid ester is reacted with nitrile in the presence of activated zinc powder under the condition of a reaction temperature of 0° C. to boiling point of the solvent, and the reaction method described in, for example, SYNTHESIS 2004, No. 16, pp 2629-2632x. can be used. As for the method of activating zinc powder, a method in which acid washing and drying are carried out in advance, or a method in which a catalytic amount of an acid such as methanesulfonic acid, etc. is included in the reaction system can be employed. 
     Preparation Method III 
     It is an exemplary method of preparing compound IIIh from intermediate IIg that is obtained from Preparation method II. 
     
       
         
         
             
             
         
       
     
     Step III-1 
     This step can be carried out by nucleophilic aromatic substitution reaction in which an aromatic nitro compound having a leaving group is reacted with β-ketoester IIg in the presence of a base under the condition of a reaction temperature of 0° C. to boiling point of the solvent, and the reaction method include that described in, for example, Synlett, (5), 883-885; 2004 and Tetrahedron, 38 (23), 3479-83; 1982. 
     As for the base used for the reaction, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, LiHMDS, NaHMDS, LDA, lithium dicyclohexylamide, lithium 2,2,6,6-tetramethylpyrrolidide, KHMDS, t-BuOK, t-BuONa and the like can be used. Preferably, it is potassium carbonate, cesium carbonate, t-BuOK, or t-BuONa. As for the solvent, examples thereof include toluene, xylene, MeCN, THF, CPME, MTBE, NMP, DMF, DMA, DMSO, sulfolane, dioxane, DME, acetone, methylethyl ketone, and a mixture thereof. Preferably, it is THF, DMF, DMA, NMP or a mixture thereof. 
     Further, the present step can be also carried out in the presence of a catalyst and a base, as described in Step III-5 or Journal of Organic Chemistry, 72 (14), 5337-5341; 2007. 
     Step III-2 
     It is a reductive cyclization step to form an indole ring following the reduction of a nitro group. This reaction can be carried out by reacting β-ketoester IIIa with a reducing agent under the condition of a reaction temperature of 0° C. to boiling point of the solvent to reduce the nitro group. As for the reducing agent used for the reaction, the condition generally used for reduction of a nitro group, for example, iron as exemplified in Synthesis, (18), 2943-2952, 2008, zinc as exemplified in Tetrahedron, 64 (40), 9607-9618, 2008, titanium (III) chloride as exemplified in Organic &amp; Biomolecular Chemistry, 3 (2), 213-215, 2005, tin (II) chloride as exemplified in Journal of Organic Chemistry, 58 (19), 5209-5220, 1993, sodium hydrosulphite as exemplified in Gazzetta Chimica Italiana, 121 (11), 499-504, 1991, and catalytic reduction condition as exemplified in Synlett, (17), 2689-2691, 2008, etc. can be employed. Preferably, the reducing agent is iron or sodium hydrosulphite. 
     Step III-3 
     It is a step of deprotecting an ester protecting group of indole-3-carboxylic acid ester IIb. As an example of an ester protecting group, a methyl group, an ethyl group, a t-butyl group, a benzyl group, a substituted benzyl group and the like can be used. Preferably, it is a t-butyl. As for the deprotection, examples thereof include a method described in “Protective Groups in Organic Synthesis” (Greene and Wuts, 4 th  edition, John Wiley &amp; Sons 2007), and it can be appropriately used according to each reaction condition. When the ester protecting group is a t-butyl, as a deprotection condition, TMSI, TMSCl, and BF 3 .OEt 2  can be used. As for the solvent, examples thereof include toluene, xylene, diethyl ether, THF, CPME, MTBE, NMP, DMF, DMA, DMSO, sulfolane, dioxane, DME, TFE and the like and a mixture thereof. Preferably, it is THF or TFE. 
     Step III-4 
     It is a step of cyclizing indole-3-carboxylic acid IIIc to carbazole based on Friedel-Crafts reaction. According to the reaction, a mixed acid anhydride is formed by using acetic anhydride, trifluoroacetic anhydride and the like, or acid chloride is formed by using thionyl chloride, oxalyl chloride, phosphorus oxychloride and the like, which results in activation of the carboxylic acid. Preferably, acetic anhydride or trifluoroacetic anhydride is used. The reaction is carried out in the absence or presence of a solvent. As for the solvent, examples thereof include toluene, xylene, diethyl ether, THF, CPME, MTBE, NMP, DMF, DMA, DMSO, sulfolane, dioxane, DME and the like and a mixture thereof. Preferably, it is THF, DMF, DMA or DME. Further, an organic base such as TEA, DIPEA, pyridine and the like can be used. 
     Thereafter, under the condition of a reaction temperature of 0° C. to boiling point of the solvent, the cyclization is carried out without a catalyst or with Bronsted acid or Lewis acid catalyst (Heterocycles 1999, 51, 2127). As for the Lewis acid catalyst, examples thereof include aluminum chloride, aluminum triflate, bismuth triflate, ytterbium triflate and BF 3 .OEt 2 . Preferably, it is BF 3 .OEt 2 . Depending on the type of a substituent group, it is also possible to carry out the reaction by applying methanesulfonic acid-phosphorus pentoxide (Eaton reagent), polyphosphoric acid and the like to indole-3-carboxylic acid ester IIIb without undergoing Step III-3. 
     Step III-5, III-6 
     The step can be carried out by reacting an aromatic acylamide compound having a leaving group with β-ketoester IIg in the presence of a base, a catalyst, and a ligand under the condition of a reaction temperature of 0° C. to boiling point of the solvent, followed by deprotection of an acyl protecting group. Examples thereof include a method described in Journal of Organic Chemistry 2007, 72, 9329-9334 and Organic Letters 10 (4), 625-628, 2008. As for the metal catalyst, copper (I) iodide and palladium acetate can be used. As for the ligand, (S)-proline, tri t-butylphosphine, bis (t-butyl) (2′-methyl[1,1′-biphenyl]-2-yl)phosphine and the like can be used. As for the base which is used for the reaction, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, LiHMDS, NaHMDS, LDA, lithium dicyclohexylamide, lithium 2,2,6,6-tetramethylpyrrolidide, potassium hexamethyldisilazide, t-BuONa, t-BuOK and the like can be used. 
     Step III-7, III-8 
     It is a step of reacting an aromatic amino compound with β-ketoester IIg to form an enamine intermediate followed by catalytic cyclization. Examples thereof include a method described in Journal of Organic Chemistry, 68 (15), 6011-6019; 2003 and European Journal of Organic Chemistry, (24), 3977-3980; 2007. 
     Alternatively, the cyclization can be carried out based on an oxidative method. For example, a reaction condition described in Angewandte Chemie, International Edition, 47 (38), 7230-7233; 2008 can be also employed, for example. 
     Step III-9 
     It is a step of synthesizing 1,3-diketone based on cyclization of p-keto ester IIg. As for the condition and reagents for the reaction, a method described in Bioorganic &amp; Medicinal Chemistry Letters, 18 (2), 568-570; 2008 wherein p-keto ester IIg is reacted in an solvent in the presence of Bronsted acid catalyst or Lewis acid catalyst, or a method of using a condensing agent such as methanesulfonic acid-phosphorus pentoxide (Eaton reagent), polyphosphoric acid and the like can be employed. 
     Step III-10, III-11 
     This step can be carried out in the same manner as Step III-1 and III-2 or Step III-5 and III-6. 
     Preparation Method IV 
     An exemplary method of producing compound IIIh wherein formula Iva is employed as a starting material. 
     
       
         
         
             
             
         
       
     
     Step IV-1, IV-3 
     It is a step of constructing di-substituted indole derivatives based on Sonogashira reaction in which a terminal alkyne is reacted with aromatic amine derivative IVa having a leaving group at ortho position in the presence of a base and a catalyst with or without a catalytic amount of a copper reagent. Specifically, examples thereof include a method described in Organic Letters, 11 (1), 221-224; 2009. The reaction is carried out in an appropriate solvent in the presence of a palladium catalyst and a ligand (or a complex thereof) with or without a base and a copper catalyst. Example of the copper catalyst used for the reaction include copper iodide. As an example of the catalyst and the ligand (or a complex thereof), palladium acetate, Pd 2 (dba) 3 , π-allyl palladium chloride dimer, PdCl 2 (CH 3 CN) 2 , PdCl 2 (PPh 3 ) 2 , trialkylproazaphosphatrane, {P(t-Bu) 3 PdBr} 2 , PPh 3 , P(o-tol) 3 , BINAP, DPPF, P(t-Bu) 3 , DavePhos, JohnPhos, c-Hexyl JohnPhos, S-Phos, X-Phos, t-ButylX-Phos, Xantphos, 4,5-bis[bis (3,5-bistrifluoromethylphenyl)phosphanyl]-9,9-dimethyl-9H-xanthene, 1,3-diallyldihydroimidazolium salt and the like can be used. As for the base used for the reaction, sodium phosphate, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, TEA, DIPEA and the like can be used. Preferably, it is cesium carbonate, TEA or DIPEA. 
     Step IV-2 
     This step corresponds to a tandem Friedel-Crafts reaction in which acylation at 3-position of di-substituted indole derivative IVb is carried out in the presence of Lewis acid catalyst under the condition of a reaction temperature of 0° C. to boiling point of the solvent, followed by intramolecular cyclization. As for the catalyst used for the reaction, examples thereof include aluminum chloride, aluminum triflate, bismuth triflate, ytterbium triflate and BF 3 .OEt 2 . Preferably, it is aluminum chloride. 
     Step IV-4 This step consists of deprotection of carboxylic acid ester comprised in di-substituted indole derivative IVc and subsequent intramolecular cyclization at 3-position of the indole either in catalytic or non-catalytic manner. As for the deprotection, examples thereof include a method described in “Protective Groups in Organic Synthesis” (Greene and Wuts, 4 th  edition, John Wiley &amp; Sons 2007), and it can be appropriately used according to the type of each protecting group. When an activated indole derivative is used for the reaction, cyclization occurs more easily so that the reaction can be carried out in a non-catalytic manner. Further, the cylclization can be also carried out by using a condensing agent such as polyphosphoric acid, methanesulfonic acid-phosphorus pentoxide (Eaton reagent) and the like. Alternatively, it is also possible that carboxylic acid is first converted into carboxylic acid chloride, a mixed acid anhydride and the like under the same condition as defined in Step III-4 and the cyclization is carried out under Friedel-Crafts condition in the presence of Lewis acid catalyst. As for the Lewis acid catalyst used for the reaction, examples thereof include aluminum chloride, aluminum triflate, bismuth triflate, ytterbium triflate and BF 3 .OEt 2 . 
     Preparation Method V 
     It is one of the methods for constructing the skeleton of the compounds having the Formula (I) in which A 5  is O, S or NH. 
     
       
         
         
             
             
         
       
     
     Step V-1 
     It is a step of arylation of cyclic ketone derivative Ib using aromatic compound Va having a leaving group. The reaction is catalytically carried out in the presence of a base with combination of a transition metal catalyst and a ligand, and the condition described in J. Am. Chem. Soc. 2000, 122, 1360-1370 and Journal of Organic Chemistry (2003), 68 (25), 9865-9866 can be used, for example. As for the base used for the reaction, examples thereof include t-BuONa, t-BuOK, LiHMDS, NaHMDS, potassium phosphate, sodium carbonate, potassium carbonate and cesium carbonate. As for the catalyst and a ligand (or a catalyst-ligand complex), palladium acetate, Pd 2 (dba) 3 , π-allylpalladium chloride dimer, PdCl 2 (CH 3 CN) 2 , PdCl 2 (PPh 3 ) 2 , trialkylproazaphosphatrane, {P(t-Bu) 3 PdBr} 2 , PPh 3 , P(o-tol) 3 , BINAP, DPPF, P(t-Bu) 3 , DavePhos, JohnPhos, c-Hexyl JohnPhos, S-Phos, X-Phos, t-ButylX-Phos, Xantphos, 4,5-bis[bis (3,5-bistrifluoromethylphenyl)phosphanyl]-9,9-dimethyl-9H-xanthene 1,3-diallyldihydroimidazolium salt and the like can be used. 
     Step V-2 
     It is a step of deprotecting a protecting group. When A 5  is O or S, a t-butyl group, a benzyl group and a substituted benzyl group can be used as a protecting group. When A 5  is O, a t-butyldimethylsilyl group and a tetrahydropyranyl group can be used. When it is NH, a t-butoxycarbonyl group, a benzyloxycarbonyl group, a methanesulfonyl group, a trifluoroacetyl group and the like can be used. As for the deprotection, examples thereof include a method described in “Protective Groups in Organic Synthesis” (Greene and Wuts, 4 th  edition, John Wiley &amp; Sons 2007), and it can be appropriately used according to the type of each protecting group. 
     Step V-3 
     It is a cyclization step of cyclic a-aryl ketone derivative Vc to a benzofuran derivative, benzothiophene or indole Vd. The reaction can be carried out under condition of using an acid catalyst or dehydrating condition. For example, the reaction condition described in Acta Pharmaceutica Hungarica (2003), 73 (3), 171-178 can be employed. In addition, depending on the type of a protecting group for hydroxyl group, it can be carried out simultaneously with the deprotection of Step V-2, as described in Heterocycles, 26 (7), 1863-71; 1987. With respect to the condition for dehydration, a combination of an organic base and an acid anhydride such as trifluoromethanesulfonic acid and the like can be used. 
     Step V-4 
     It is a step of oxidation at benzyl at 11-position of tetracyclic compound Vd. This step is carried out by applying an oxidizing agent to a substrate in a solvent in the presence or absence of a catalyst under the condition of a reaction temperature of −20° C. to boiling point of the solvent. As for the reaction condition, the method described in Journal of Medicinal Chemistry, 51 (13), 3814-3824; 2008, etc. can be employed. 
     As for the oxidizing agent and the catalyst used for the reaction, DDQ, peracid such as, mCPBA and the like, cerium ammonium nitrate (IV) (CAN), permanganate such as potassium permanganate, barium permanganate and the like, sodium chlorite, hydrogen peroxide, N-hydroxyphthalimide and the like can be used alone or in a combination thereof. As for the solvent used for the reaction, examples thereof include water, t-butanol, acetonitrile, tetrahydrofuran, dichloromethane, ethyl acetate and a mixture thereof. 
     Preparation Method VI 
     It is an exemplary method of constructing the skeleton of the compounds that are represented by the Formula (I) in which A 5  is S. 
     
       
         
         
             
             
         
       
     
     Step VI-1 
     It is a reaction to construct a benzothiophene ring based on the reaction between ylide VIa having a thiol at ortho position and acyl chloride VIb. The reaction can be carried out in the presence of a base, and the condition include that described in Synthesis, (2), 155-7; 1988, for example. As for the base, examples thereof include n-butyl lithium, sodium methylate and triethylamine. 
     Step VI-2 
     It is a reaction for the synthesis of an aromatic carboxylic acid. The reaction can be carried out by metallization like addition of lithium or magnesium based on exchange between halogen and metal in the presence of a base, followed by carboxylation using carbonate gas, dry ice, etc. The reaction condition as described in Journal of Organic Chemistry (2008), 73 (19), 7785-7788 can be employed. As for the base, n-butyl lithium, s-butyl lithium, t-butyl lithium, a Grignard reagent, and various ate complexes can be used. Alternatively, as described in e-EROS Encyclopedia of Reagents for Organic Synthesis 2001 (electronic edition; http: //www3.interscience.wiley.com/cgi-bin/mrwhome/104554785/HOME), carboxylation condition using a transition metal catalyst can be also employed. 
     Step VI-3 
     This step corresponds to intramolecular cyclization at 3-position of di-substituted benzothiophene derivative VId either in catalytic or non-catalytic manner. For example, the reaction condition as described in Journal of the American Chemical Society, 130 (23), 7286-7299; 2008 can be employed. The reaction can be carried out by using a condensing agent such as polyphosphoric acid, methanesulfonic acid-phosphorus pentoxide (Eaton reagent) and the like. Alternatively, it is also possible that carboxylic acid is first converted into carboxylic acid chloride, a mixed acid anhydride and the like and the cyclization is carried out under Friedel-Crafts condition in the presence of Lewis acid catalyst. As for the Lewis acid catalyst used for the reaction, examples thereof include aluminum chloride, aluminum triflate, bismuth triflate, ytterbium triflate and BF 3  OEt 2 . 
     Preparation Method VII Conversion and Modification of Functional Groups 
     To the functional groups PR 1  to PR 10  in the Formula (I) of the present invention, various substituent groups can be introduced based on a method of converting and modifying a functional group that is well known to a skilled person in the pertinent art. Hereinbelow, representative examples of functional group conversion will be explained. Further, although the following reaction scheme is specific in that examples of PR 8  and PR 9  are given for the tetracyclic compound that is already constructed, it can be also carried out to an intermediate during any steps explained in Preparation methods I to VI above or to a final compound. Further, it can be carried out at any substitution position of PR 1  to PR 4  and R 6  to PR 10 . 
     In the following formula, Q 1  and Q 2  represent any substituent group which constitutes PR 1  to PR 4  and R 6  to PR 10 . 
     
       
         
         
             
             
         
       
     
     Step VII-1 
     It is a step of deprotecting a protecting group for an aromatic hydroxyl group. As an example of the protecting group, a methyl group, a t-butyl group, a benzyl group, a substituted benzyl group, a t-butyldimethylsilyl group, a tetrahydropyranyl group and the like can be used. Preferably, it is a methyl group. As for the deprotection, examples thereof include a method described in “Protective Groups in Organic Synthesis” (Greene and Wuts, 4 th  edition, John Wiley &amp; Sons 2007), and it can be appropriately used according to the type of each protecting group. When a methyl group is used as a protecting group, various reaction conditions can be used selectively for the deprotection depending on reactivity. Examples thereof include heating in the presence of pyridine hydrochloric acid salt, heating in the presence of a solvent with dodecane thiol and sodium methylate and heating in the presence of a solvent with anhydrous lithium halide, boron tribromide, TMSI and the like. 
     Step VII-2 
     It is one of the methods for introducing a substituent group based on formation of ether bond with an aromatic hydroxyl group. For the formation of an ether bond, Mitsunobu reaction described in a known literature (Mitsunobu, et. al., Synthesis, Vol. 1, page 1, 1981) or a similar method can be used. Specifically, the reaction is carried out in the presence of a phosphorus compound and an azo compound in a solvent under the condition of a reaction temperature of −78° C. to boiling point of the solvent. As for the phosphorus compound, examples thereof include PPh 3  and tri-n-butylphosphine. As for the azo compound, examples thereof include DEAD, TMAD and diisopropyl azodicarboxylic acid. Also, by using them in any combination, the target compound can be obtained. 
     Step VII-3 
     It is a step of carrying out trifluoromethane sulfonylation on an aromatic hydroxyl group. The reaction is carried out by reacting with a reacting reagent such as trifluoromethanesulfonic acid and the like in the presence of a base with or without a solvent under the condition of a reaction temperature of −20° C. to boiling point of the solvent. As for the base used for the reaction, TEA, DIPEA, pyridine, 2,6-lutidine, dimethylaminopyridine and the like can be used. Preferably, pyridine is used without any solvent. The obtained trifluoromethanesulfonic acid ester VIId is a good leaving group and can be used for various derivatization. 
     Step VII-4 
     It is a step of obtaining sulfamic acid ester by carrying out sulfamoylation on an aromatic hydroxyl group. The reaction is carried out by reacting with a reacting reagent such as sulfamoyl chloride and the like in the presence of a base with a solvent under the condition of a reaction temperature of −20° C. to boiling point of the solvent. As for the base used for the reaction, sodium hydride, TEA, DIPEA, pyridine, 2,6-lutidine, dimethylaminopyridine and the like can be used. Preferably, it is sodium hydride. The obtained sulfamic acid ester VIIe is a substrate for the thiaFries rearrangement of Step VII-5 and can be used for various derivatization. 
     Step VII-5 
     This step corresponds to rearrangement of a sulfamoyl group to a neighboring position in the presence of a Lewis acid catalyst under the condition of a reaction temperature of 0° C. to boiling point of the solvent when the neighboring position of the sulfamic acid ester is unsubstituted (i.e., C—H), i.e., a reaction called thiaFries rearrangement. As for the catalyst used for the reaction, aluminum chloride, aluminum triflate, bismuth triflate, ytterbium triflate, BF 3 .OEt 2  and the like can be used. Preferably, it is aluminum chloride. 
     Step VII-6 
     
       
         
         
             
             
         
       
     
     It is another step of introducing a substituent group based on formation of an ether bond. According to the present step, a reagent having an appropriate leaving group such as alkyl halide and the like is subjected to nucleophilic reaction with the hydroxyl group of compound VIIb in the presence of an appropriate base to form an ether bond. As for the base, examples thereof include an inorganic base such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, calcium hydride and the like or an organic base such as pyridine, TEA, DIPEA and the like. 
     Further, by using aryl halide, aryl borate and the like as a reagent having a leaving group, formation of an diaryl ether bond can be also achieved and used. When reactivity is not satisfactory, a catalyst such as copper powder, copper acetate, copper iodide and the like or a ligand such as phenanthroline, trans-1,2-cyclohexanediamine and the like can be used. 
     
       
         
         
             
             
         
       
     
     Step VII-7 
     It is a reaction for forming a bond between aryl and a hetero atom by using compound VIIg having a leaving group. The reaction is carried out in an appropriate solvent inert to the reaction, in the presence of a base. As for the leaving group LG, a halogen, triflate and the like can be used. As for the solvent, examples thereof include toluene, xylene, n-hexane, cyclohexane, DMF, DMA, EtOAc, DMSO, NMP, THF, DME, dioxane, acetonitrile and the like and a mixture thereof. As for the base to be used for the reaction, examples thereof include t-BuONa, t-BuOK, LiHMDS, NaHMDS, KHMDS, potassium phosphate, sodium carbonate, potassium carbonate and cesium carbonate. This step can be also carried out by using a catalyst and a ligand. As for the catalyst and a ligand (or a catalyst-ligand complex), palladium acetate, Pd 2 (dba) 3 , π-allylpalladium chloride dimer, PdCl 2 (CH 3 CN) 2 , PdCl 2 (PPh 3 ) 2 , trialkylproazaphosphatrane, {P(t-Bu) 3 PdBr} 2 , PPh 3 , P(o-tol) 3 , BINAP, DPPF, P(t-Bu) 3 , DavePhos, JohnPhos, c-Hexyl JohnPhos, S-Phos, X-Phos, t-ButylX-Phos, Xantphos, 4,5-bis[bis (3,5-bistrifluoromethylphenyl)phosphanyl]-9,9-dimethyl-9H-xanthene, 1,3-diallyldihydroimidazolium salt and the like can be used, for example. 
     Step VII-8 
     When the reaction product of Step VII-7 is thio ether VIIh, it is possible to obtain sulfoxide or sulfone compound VIIj by oxidation with m-chloro perbenzoic acid, oxone, TEMPO and the like. 
     Step VII-9 
     
       
         
         
             
             
         
       
     
     It is a reaction for forming a bond between aryl and SP 2  carbon or a bond between aryl and SP 3  carbon in which compound VIIg having a leaving group is used. The reaction is carried out in an appropriate solvent inert to the reaction, in the presence of a base. As for the leaving group LG, a halogen, triflate and the like can be used. As for the solvent, examples thereof include toluene, xylene, n-hexane, cyclohexane, DMF, DMA, EtOAc, DMSO, NMP, THF, DME, dioxane, acetonitrile, water, isopropanol and the like and a mixture thereof. As for the base to be used for the reaction, examples thereof include t-BuONa, t-BuOK, LiHMDS, NaHMDS, KHMDS, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, TEA and DIPEA. This step can be also carried out by using a catalyst and a ligand. As for the catalyst and a ligand (or a catalyst-ligand complex), palladium acetate, Pd 2 (dba) 3 , π-allylpalladium chloride dimer, PdCl 2 (CH 3 CN) 2 , PdCl 2 (PPh 3 ) 2 , trialkylproazaphosphatrane, {P(t-Bu) 3 PdBr} 2 , PPh 3 , P(o-tol) 3 , BINAP, DPPF, P(t-Bu) 3 , DavePhos, JohnPhos, c-Hexyl JohnPhos, S-Phos, X-Phos, t-ButylX-Phos, Xantphos, 4,5-bis[bis (3,5-bistrifluoromethylphenyl)phosphanyl]-9,9-dimethyl-9H-xanthene, 1,3-diallyldihydroimidazolium salt and the like can be used, for example. 
     
       
         
         
             
             
         
       
     
     Step VII-10 
     It is a carboxylation reaction using compound VIIg having a leaving group. The reaction is carried out by reacting with formic acid (or a synthetic equivalent thereof) in an appropriate solvent inert to the reaction, in the presence of a base and a catalyst. As for the leaving group LG, a halogen, triflate and the like can be used. The solvent and the catalyst can be selected and used in the same manner as Step VII-9. 
     Step VII-11 
     It is an amidation reaction using carboxylic acid VIIm. Specifically, the reaction can be carried out by dehydrating condensation reaction using various amines such as ammonia, primary amines, secondary amines, hydrazines, substituted hydrazines and the like. The reaction is carried out in the presence of an acid halogenating agent or a dehydrating condensing agent in an aprotic solvent under the condition of a reaction temperature of −20° C. to boiling point of the solvent, with or without an active esterifying agent and a base. 
     As for the acid halogenating agent, examples thereof include oxalyl chloride and thionyl chloride. As for the dehydrating condensing agent, examples thereof include 1,3-dicyclohexylcarbodiimide (DCC), 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), bromo-tris (pyrrolidino)-phosphonium hexafluorophosphate (PyBrOP), EDC and (benzotriazolyloxy)tripyrrolidino-phosphonium=hexafluorophosphate (PyBOP). As for the active esterifying agent, examples thereof include HOBt, di(N-succinimidyl) carbonate and carbonyl diimidazole. As for the base, examples thereof include TEA, DIPEA and DBU. As for the solvent, examples thereof include DMF, DMA, DCM, acetone, THF, dioxane, DME, ethyl acetate, MeCN, and a mixture thereof. 
     Step VII-12 
     
       
         
         
             
             
         
       
     
     It is a step of forming a bond between aryl and SP carbon using compound VIIo having a leaving group. The reaction is carried out by reacting terminal alkyne in an appropriate solvent in the presence of a base and a catalyst with or without a catalytic amount of a copper reagent, and the reaction is referred to as Sonogashira reaction. The reagents and the condition for the reaction are as defined in Step IV-1 and Step IV-3. As a variant of Sonogashira reaction, examples thereof include a method disclosed in Tetrahedron, 63 (43), 10671-10683; 2007. Specifically, by having secondary amines and the like in a reaction system and using propargyl bromide as an alkyne, a propargyl amine can be introduced. 
     Step VII-13 
     
       
         
         
             
             
         
       
     
     It is a reaction of forming a bond between aryl and CN by using compound VIIo having a leaving group. The reaction can be carried out by adding CN −  source in an appropriate solvent in the presence of a copper, zinc or palladium catalyst, with or without a ligand, in view of the reaction condition shown in Organic Letters, 10 (23), 5325-5328; 2008, Tetrahedron Letters, 49 (32), 4693-4694; 2008 and Bioorganic &amp; Medicinal Chemistry, 16 (13), 6489-6500; 2008. As for the CN − -source, copper (I) cyanide, zinc (II) cyanide, iron (III) hexacyanide, sodium cyanide, potassium cyanide and the like can be used. 
     Synthesis of Starting Materials 
     Some of the starting materials for the present invention are novel compounds, and they can be easily synthesized in the same manner as known reacting compounds or according to the method well known to a skilled person in the art. 
     Hereinabove, examples of a method of preparing the compounds having the Formula (I) according to the present invention are described. However, separation and purification of the target compounds that are described in detail in each reaction step can be performed by applying common chemical treatments such as extraction, concentration, removal by distillation, crystallization, filtration, recrystallization, various chromatography, etc. 
     Pharmaceutical of the Present Invention 
     The pharmaceutical composition of the present invention comprises a pharmaceutically acceptable carrier, in addition to the compound that is selected as being useful for the invention. In the present specification, the term “pharmaceutically acceptable carrier” means one or more type of appropriate solid or liquid vehicle, diluent or an encapsulating material which is suitable for administration to mammals. In the present specification, the term “acceptable” means that it does not cause any reaction to substantially reduce the pharmaceutical efficacy of a composition under normal condition for use, and the components of the composition and the subject compound can be mixed well with each other. The pharmaceutically acceptable carrier should have substantially high purity and substantially low toxicity so that it can be suitably administered to a subject to be treated, preferably an animal, and more preferably a mammal. 
     As the materials which can be used as a pharmaceutically acceptable carrier, examples thereof include sugars such as lactose, glucose, sucrose, and the like; starch such as corn starch, potato starch and the like; cellulose and cellulose derivatives such as sodium carboxy methyl cellulose, ethyl cellulose, methyl cellulose and the like; tragacanth rubber powder; malt; gelatin; talc; solid lubricating agent such as stearic acid or magnesium stearate and the like; calcium sulfate; vegetable oils such as peanut oil, cotton seed oil, sesame oil, olive oil, corn oil, plant oil, cacao oil, and the like; polyhydric alcohols such as propylene glycol, glycerin, sorbitol, mannitol, polyethylene glycol and the like; alginic acid; an emulsifying agent such as TWEEN; humectant such as lecithin and the like; colorant; flavor; tabletting agent; stabilizer, anti-oxidant; preservative; pyrogen-free water; aqueous isotonic solution and phosphate buffer solution. 
     When the pharmaceutical composition of the present invention is used as an ALK inhibitor or a therapeutic or prophylactic agent for a proliferative disorder, or used against depression or cognitive function disorder, as an administration route, oral, rectal, parenteral (intravenous, intramuscular, subcutaneous), intracisternal, intravaginal, intraperitoneal, intrabladder, topical (drop, powder, ointment, gel or cream) administration or administration via inhalation (mouth or nasal spray) and the like can be considered. As for the administration form, examples thereof include a tablet, a capsule, a granule, powder, a pill, an aqueous or non-aqueous oral solution and suspension, and a parenteral solution which is filled in a container suitable to be divided into several small dosages. In addition, the administration form can be modified for various administration routes including subcutaneous transplant which gives controlled release of a drug compound. 
     The aforementioned preparation is prepared according to a method generally known in the art by using additives such as a vehicle, a lubricating agent (i.e., coating agent), a binding agent, a disintegrating agent, a stabilizing agent, a corrigent for taste and smell, a diluent and the like. 
     As a vehicle, examples thereof include starch such as starch, potato starch, corn starch, lactose, crystalline cellulose and calcium hydrogen phosphate. 
     As a coating agent, examples thereof include ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, shellac, talc, caranuba wax and paraffin. 
     As a binding agent, examples thereof include polyvinyl pyrrolidone, Macrogol and the compounds described above as a vehicle. 
     As a disintegrating agent, examples thereof include the compounds described as a vehicle in the above and a chemically modified starch or cellulose such as sodium croscarmellose, sodium carboxymethyl starch and crosslinked polyvinyl pyrrolidone. 
     As a stabilizing agent, examples thereof include paraoxy benzoic acid esters such as methyl paraben, propyl paraben and the like; alcohols such as chlorobutanol, benzyl alcohol, phenylethyl alcohol and the like; benzalkonium chloride; phenols such as phenol, cresol and the like; thimerosal; dehydroacetic acid; and sorbic acid. 
     As a corrigent for taste and smell, examples thereof include a sweetener, an acid tasting agent, a flavor and the like that are commonly used in the art. 
     Further, as a solvent to prepare a liquid preparation, examples thereof include ethanol, phenol, chlorocresol, purified water and distilled water. 
     As a surface active agent or an emulsifying agent, examples thereof include polysorbate 80, polyoxyl 40 stearate and lauromacrogol. 
     When the pharmaceutical composition of the present invention is used as an ALK inhibitor or a therapeutic or prophylactic agent for a proliferative disorder, or used against depression or cognitive function disorder, the use amount of the compounds of the present invention or salts or solvates thereof varies depending on symptom, age, body weight, relative health state of a subject, administration of other drug compounds, administration method and the like. For example, the amount which is generally effective for a patient (i.e., warm-blooded animal, in particular human) is, in an effective component (i.e., the compound of the present invention that is represented by the Formula (I)), preferably 0.001 to 1000 mg per 1 kg body weight per day, more preferably 0.01 to 300 mg per 1 kg body weight per day in case of an orally administered agent, and dosage per day is preferably in the range of 1 to 800 mg for an adult patient with normal body weight. In case of a parenterally administered agent, it is preferably 0.001 to 1000 mg per 1 kg body weight per day, and more preferably, 0.01 to 300 mg per 1 kg body weight per day. It is preferable to administer them once a day or in divided dosages a day, depending on symptom of a subject to be treated. 
     EXAMPLE 
     Hereinbelow, the present invention will be explained in greater detail in view of the following examples. However, the present invention is not limited by the examples. 
     NMR Analysis 
     NMR analysis was carried out by using JNM-EX270 (270 MHz, manufactured by JEOL), JNM-GSX400 (400 MHz, manufactured by JEOL), or 400 MR (400 MHz, manufactured by Varian). NMR data was expressed in ppm (parts per million; 6), while it was compared with the deuterium lock signal obtained from a sample solvent. 
     Mass Spectrum 
     The measurement was carried out by using JMS-DX303 or JMS-SX/SX102A (both manufactured by JEOL). 
     High Performance Liquid Chromatography-Mass Spectrum Data (LC-MS) 
     Measurement was carried out by using Micromass (ZMD, manufactured by Micromass) equipped with 996-600E gradient high performance liquid chromatography (manufactured by Waters) or Micromass (ZQ, manufactured by Micromass) equipped with 2525 gradient high performance liquid chromatography (manufactured by Waters). 
     One of the following conditions that are described in the Table 1 below was taken as a condition for high performance liquid chromatography. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Analysis 
                   
                   
                 Column  
                   
                 Flow Rate 
                 Detection 
               
               
                 Condition 
                 Apparatus 
                 Column used 
                 Temperature 
                 Mobile phase, Gradient 
                 (mL/min) 
                 Wavelength 
               
               
                   
               
             
            
               
                 A 
                 ZMD 
                 Cadenza CD-C18 
                 35 deg. 
                 A) 0.05% TFA, H2O  
                 1.5 
                 210-400 nm 
               
               
                   
                   
                 (intake) 3.0 mml · D. × 
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 30 mm, 3 um 
                   
                 (A/B): 95/5 =&gt; 0/100 (3.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (1 min) 
                   
                   
               
               
                 B 
                 ZMD 
                 Cadenza CD-C18 
                 35 deg. 
                 A) 0.05% TFA, H2O  
                 1.0 
                 210-400 nm 
               
               
                   
                   
                 (intake) 3.0 mml · D. × 
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 30 mm, 3 um 
                   
                 (A/B): 95/5 =&gt; 0/100 (9.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (2.5 min) 
                   
                   
               
               
                 C 
                 ZQ 
                 Chromolith Flash RP- 
                 Room Temp. 
                 A) 10 mM AcONH4, H2O  
                 2.0 
                 210-400 nm 
               
               
                   
                   
                 18e (Merck KGaA) 
                   
                 B) MeOH 
                   
                 PDA total 
               
               
                   
                   
                 4.6 mml · D. × 25 mm 
                   
                 (A/B): 95/5 =&gt; 0/100 (3 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (2 min) 
                   
                   
               
               
                 D 
                 ZQ 
                 Chromolith Flash RP- 
                 Room Temp. 
                 A) 10 mM AcONH4, H2O  
                 2.0 
                 210-400 nm 
               
               
                   
                   
                 18e (Merck KGaA) 
                   
                 B) MeCX 
                   
                 PDA total 
               
               
                   
                   
                 4.6 mml · D. × 25 mm 
                   
                 (A/B): 95/5 =&gt; 0/100 (3 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (2 min) 
                   
                   
               
               
                 F 
                 ZQ 
                 Cadenza CD-C18 
                 35 deg. 
                 A) 0.05% TFA, H2O  
                 1.5 
                 210-400 nm 
               
               
                   
                   
                 (intake) 3.0 mml · D. × 
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 30 mm, 3 um 
                   
                 (A/B): 95/5 =&gt; 0/100 (3.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (1min) 
                   
                   
               
               
                 E 
                 ZQ 
                 Cadenza CD-C18 
                 35 deg. 
                 A) 0.05% TFA, H2O  
                 1.0 
                 210-400 nm 
               
               
                   
                   
                 (Intake) 3.0 mml · D. × 
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 30 mm, 3 um 
                   
                 (A/B): 95/5 =&gt; 0/100 (9.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (2.5 min) 
                   
                   
               
               
                 I 
                 ZQ 
                 Ascentis Express C18 
                 Room Temp. 
                 A) 10 mM AcONH4, H2O  
                 1.0 
                 210-400 nm 
               
               
                   
                   
                 (Sigma Aldrich) 
                   
                 B) MeOH 
                   
                 PDA total 
               
               
                   
                   
                 2.1 mml · D. × 50 mm 
                   
                 (A/B): 95/5 =&gt; 0/100 (9.5 min) =&gt;  
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (1 min) 
                   
                   
               
               
                 S 
                 ZQ 
                 Sunfire C18 (Waters) 
                 Room Temp. 
                 A) 0.05% TFA, H2O  
                 4.0 
                 200-400 nm 
               
               
                   
                   
                 4.5 mml · D. × 50 mm,  
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 5 um 
                   
                 (A/B): 90/10 =&gt; 5/95 (3.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 90/10 (1 min) =&gt; 90/10 (0.5 min) 
                   
                   
               
               
                 T 
                 ZQ 
                 Sunfire C18 (Waters) 
                 Room Temp. 
                 A) 0.05% TFA, H2O 
                 4.0 
                 200-400 nm 
               
               
                   
                   
                 4.5 mml · D. × 50 mm,  
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 5 um 
                   
                 (A/B): 90/10 =&gt; 5/95 (2 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 5/95 (1.5 min) =&gt; 90/10 (1.0 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 90/10 (0.5 min) 
                   
                   
               
               
                 U 
                 ZQ 
                 WAKOsil 3C18 AR, (Wako 
                 Room Temp. 
                 A) 0.05% TFA, H2O  
                 2.0 
                 210-400 nm 
               
               
                   
                   
                 Pure Chemical Industries, 
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 Ltd.) 4.6 mml · D. × 30 mm 
                   
                 (A/B): 90/10 =&gt; 90/10 (0.2 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 5/95 (3.1 min) =&gt; 5/95 (1.4 min) 
                   
                   
               
               
                 W 
                 ZMD 
                 Sunfire C18 (Waters) 
                 Room Temp. 
                 A) 0.05% TFA, H2O  
                 4.0 
                 200-400 nm 
               
               
                   
                   
                 4.5 mml · D. × 50 mm,  
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 5 um 
                   
                 (A/B): 90/10 =&gt; 5/95 (3.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 90/10 (1 min) =&gt; 90/10 (0.5 min) 
                   
                   
               
               
                 Y 
                 ZMD 
                 Sunfire C18 (Waters) 
                 Room Temp. 
                 A) 0.05% TFA, H2O  
                 2.0 
                 210-400 nm 
               
               
                   
                   
                 4.5 mml · D. × 50 mm,  
                   
                 B) 0.05% TFA, MeCN 
                   
                 PDA total 
               
               
                   
                   
                 7 um 
                   
                 (A/B): 90/10 =&gt; 0/100 (3.5 min) =&gt; 
                   
                   
               
               
                   
                   
                   
                   
                 0/100 (1 min) 
               
               
                   
               
            
           
         
       
     
     Microwave Reaction 
     The reaction was carried out by using a snap cap reaction vial together with an Explorer™ (manufactured by CEM Microwave Technology) or an initiator (manufactured by Biotage). Maximum output setting includes cooling of the reaction vessel by air in order to avoid temperature increase caused by microwave irradiation. 
     Commercially available reagents were obtained and used without any further purification. The room temperature indicates the temperature range of between about 20 to 25° C. All the non-aqueous reaction was carried out in anhydrous solvent under nitrogen or argon atmosphere. For concentration under reduced pressure or removal of a solvent by distillation, a rotary evaporator was used. 
     For preparing the compounds, when there is a possibility of having an undesirable side reaction, a functional group was protected using a protecting group to produce a target molecule, and the protecting group was removed later, if desired. Selection, addition and removal of a protecting group were carried out according to the method described in the literature [Greene and Wuts, “Protective Groups in Organic Synthesis” (4 th  edition, John Wiley &amp; Sons 2007)], for example. 
     Example 1 
     Compound A2 
     7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     7-Methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 209 g, 1.18 mol), tetrabutylammonium hydrogen sulfate (40 g, 0.118 mol) and methyl iodide (162 g, 2.60 mol) were suspended in THF (500 ml) at room temperature. Under stirring, the mixture was added with 50% aqueous solution of potassium hydroxide (400 g) over 5 min. Reflux occurred as the inner temperature rapidly increases. Once the inner temperature stopped to increase, stirring was continued for 45 min. The reaction solution was diluted with distilled water (1 L) and extracted twice with CPME (1.5 L). The combined organic layer was washed (distilled water 1 L×3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was recrystallized with MeOH (1 L) and distilled water (500 ml) to obtain the title compound as a colorless needle-like crystal (177 g, 73%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 1.43 (6H, s), 2.65 (2H, t, 12 Hz), 3.02 (2H, t, 12 Hz), 3.79 (3H, s), 6.74 (1H, m), 6.87 (1H, m), 7.24 (1H, m). 
     LCMS: m/z 205 [M+H] +   
     Example 2 
     Compound A3-1, Compound A3-2 
     3-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     1-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 66.2 g, 324 mmol) and 3-bromophenylhydrazine hydrochloric acid salt (71.0 g, 318 mmol) were dissolved in AcOH (350 ml) and refluxed under stirring for 6 hr. The reaction solvent was removed by distillation under reduced pressure to obtain the crude product as a mixture of the title compound A3-1 and A3-2. 
     Example 3 
     Compound A4 
     3-Bromo-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The crude product obtained from the above (i.e., mixture of A3-1 and A3-2) was dissolved in a mixture solvent of THF (450 ml) and distilled water (50 ml), added once with DDQ (115 g, 509 mmol), and then stirred at room temperature for 1 hr. The reaction mixture was diluted with CPME 3L, and the organic layer was washed three times with 0.5 N aqueous solution of sodium hydroxide (1 L) and twice with distilled water (1 L) in order and dried over anhydrous sodium sulfate. The organic layer was concentrated to 500 ml under reduced pressure. The precipitated product was collected by filtration and washed with a small amount of CPME to obtain the title compound as a yellow crystal (48 g, 40%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 1.73 (6H, s), 3.90 (3H, s), 7.06-7.09 (1H, m), 7.32-7.38 (2H, m), 7.65-7.66 (1H, m), 8.09-8.17 (2H, m), 12.32 (1H, br. s). 
     LCMS: m/z 370, 372 [M+H]+ 
     Example 4 
     Compound AA1 
     4-Methoxy-2-(3-trimethylsilanylprop-2-ynyl)-benzoic acid methyl ester 
     
       
         
         
             
             
         
       
     
     To the THF (16 ml) solution of 2-bromomethyl-4-methoxy-benzoic acid methyl ester (961 mg, 4.09 mmol), triphenylphosphine (107 mg, 0.1 eq.), cesium carbonate (1.87 g, 1.4 eq.), copper iodide (59 mg, 0.076 eq.) and tris (dibenzylideneacetone) dipalladium (86 mg, 0.023 eq.) were added, degassed, flushed with nitrogen gas, added with trimethylsilylacetylene (734 μl, 1.3 eq.), and then stirred overnight at 55° C. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (brown oily substance, 606 mg, 54%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 7.93 (1H, d, J=8.8 Hz), 7.33 (1H, d, J=2.6 Hz), 6.78 (1H, dd, J=8.8, 2.6 Hz), 4.09 (2H, s), 3.86 (3H, s), 3.84 (3H, s), 0.14 (9H, s). 
     LCMS: m/z 277 [M+H] +   
     HPLC retention time: 3.30 min (analysis condition U) 
     Example 5 
     Compound AA2 
     2-(1,1-Dimethyl-3-trimethylsilanylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester 
     
       
         
         
             
             
         
       
     
     To the toluene (4 ml) solution of 4-methoxy-2-(3-trimethylsilanyl-prop-2-ynyl)-benzoic acid methyl ester (Compound AA1, 273 mg, 0.988 mmol), sodium bis (trimethylsilyl) amide (2.1 ml, 1.9 m solution, 4 eq.) and iodomethane (308 μl, 5 eq.) were added at −78° C. After allowing the reaction temperature to increase to the room temperature, the mixture was stirred for 2 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow oily substance, 226 mg, 75%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 7.45 (1.0H, d, J=8.4 Hz), 7.09 (1.1H, d, J=2.6 Hz), 6.75 (1H, m), 3.84 (3H, s), 3.82 (3H, s), 1.70 (6H, s), 0.14 (9H, s) 
     LCMS: m/z 305 [M+H] +   
     HPLC retention time: 3.38 min (analysis condition U) 
     Example 6 
     Compound AA3 
     2-(1,1-Dimethylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester 
     
       
         
         
             
             
         
       
     
     To the THF (18 ml) solution of 2-(1,1-dimethyl-3-trimethylsilanylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester (Compound AA2, 912 mg, 3 mmol), tetrabutylammonium fluoride (2.061 g, 2.6 eq.) was added, and then stirred for 3 hr at room temperature. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow oily substance, 524 mg, 75%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 7.44 (1H, d, J=8.4 Hz), 7.05 (1H, d, J=2.3 Hz), 6.76 (1H, dd, J=8.4, 2.3 Hz), 3.84 (3H, s), 3.82 (3H, s), 1.73 (6H, s) 
     LCMS: m/z 223 [M+H] +   
     HPLC retention time: 2.55 min (analysis condition U) 
     Example 7 
     Compound AA4 
     2-[1-(6-Cyano-1-methanesulfonyl-1H-indol-2-yl)-1-methylethyl]-4-methoxy-benzoic acid methyl ester 
     
       
         
         
             
             
         
       
     
     To the DMF (2 ml) solution of 2-(1,1-dimethylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester (Compound AA3, 134 mg, 0.577 mmol) and N-(2-bromo-5-cyanophenyl)methanesulfonamide (Compound AA5, 167 mg, 1.05 eq.), copper iodide (9 mg, 0.08 eq.) and TEA (129 μl, 1.6 eq.) were added, degassed and flushed with nitrogen gas, added with dicholorobis (triphenylphosphine) palladium (20 mg, 0.05 eq.), and then degassed and flushed again with nitrogen gas. After stirring for 2 hr at 90° C., the reaction solution was added with water, extracted with ethyl acetate. The organic layer was washed with an brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white solid, 152 mg, 62%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.19 (1H, dd, J=0.6, 0.6 Hz), 7.84 (1H, dd, J=8.0, 0.6 Hz), 7.67 (1H, dd, J=8.0, 1.3 Hz), 7.13 (1H, d, J=8.4 Hz), 6.99 (1H, s), 6.96 (1H, br. s), 6.85 (1H, dd, J=8.4, 2.5 Hz), 3.78 (3H, s), 3.12 (3H, s), 3.09 (3H, br. s), 1.89 (6H, s). 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 2.77 min (analysis condition U) 
     Example 8 
     Compound AA5 
     N-(2-Bromo-5-cyanophenyl)methanesulfonamide 
     
       
         
         
             
             
         
       
     
     To a mixture of 3-amino-4-bromo-benzonitrile (1.98 g, 10 mmol), TEA (5.06 g, 50 mmol), and methylene chloride (50 ml), mesyl chloride (2.71 ml, 35 mmol) was added at 0° C. and the mixture was stirred at room temperature for 30 min. Water was added to the reaction solution, which was then extracted with dichloromethane. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with tetrahydrofuran (100 ml), water (400 l) and sodium hydride (540 mg, 15.5 mmol), and stirred at room temperature for 16 hr. To the reaction solution, saturated aqueous solution of ammonium chloride (200 ml) was added followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (2.48 g, 90%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 9.82 (1H, s), 7.87 (1H, d, J=4 Hz), 7.75 (1H, d, J=8 Hz), 7.70 (1H, dd, J=8 Hz, 4 Hz), 3.14 (3H, s) 
     HPLC retention time: 1.63 min (analysis condition U) 
     Example 9 
     Compound AA6 
     2-(1-Hydroxy-1-methylethyl)-1H-indole-6-carbonitrile 
     
       
         
         
             
             
         
       
     
     To N-(2-bromo-5-cyanophenyl)methanesulfonamide (Compound AA5, 230 mg, 1 mmol), 3-methyl-2-butyn-3-ol (0.15 ml, 1.5 mmol), X-Phos (72 mg, 15% mol), PdCl 2 (CH 3 CN) 2  (13 mg, 5% mol) and cesium carbonate (390 mg, 2 mmol), DMA (2 ml) was added, and the mixture was stirred at 100° C. for 3 hr. Water and 5 N hydrochloric acid solution were added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (130 mg, 75%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 8.76 (1H, s), 7.68 (1H, s), 7.60 (1H, d, J=8 Hz), 7.32 (1H, dd, J=8 Hz, 4 Hz), 6.37 (1H, m), 1.93 (1H, s), 1.70 (6H, s) 
     LCMS: m/z 201 [M+H] +   
     HPLC retention time: 2.12 min (analysis condition U) 
     Example 10 
     Compound A5-1 
     3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was synthesized from Compound A4. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.30 (1H, s), 10.21 (1H, s), 8.06-8.11 (1H, m), 8.01-8.05 (1H, m), 7.62-7.66 (1H, m), 7.32-7.37 (1H, m), 7.08-7.12 (1H, m), 6.84-6.90 (1H, m), 1.69 (6H, s). 
     LCMS: m/z 356, 358 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition U) 
     Example 11 
     Compound A5-2 
     8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     (Method 1) 3-Bromo-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (Compound A4, 10.45 g, 28.2 mmol) and copper (I) cyanide (5.0 g, 50.2 mmol) were dissolved in NMP (100 ml), followed by stirring at 170° C. for 17 hr. The reaction mixture was suspended in ethyl acetate (500 mL) and distilled water (200 mL). The insoluble matters were removed by Celite filtration and washed twice with ethyl acetate (300 mL×2). The organic layer was washed once with an aqueous solution of disodium EDTA (200 mL) and twice with saturated brine (200 mL) in order, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to yield a product, which was suspended and washed with a small amount of CPME to obtain the title compound as a colorless crystal (6.58 g, 73%). 
     (Method 2) To the THF (5.6 ml) solution of 2-[1-(6-cyano-1-methanesulfonyl-1H-indol-2-yl)-1-methylethyl]-4-methoxy-benzoic acid methyl ester (Compound AA4, 138 mg, 0.324 mmol), tetrabutylammonium fluoride (514 mg, 6 eq.) was added, and the mixture was stirred at room temperature overnight. Thereafter, 2 M aqueous solution of sodium hydroxide (5.6 ml) was added to the mixture, which was then stirred for 4 hr, added with 1 M HCl, and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were dissolved in ethyl acetate (10 ml) and added with e 4 M HCl and ethyl acetate solution (10 ml) followed by stirring at room temperature for 30 min. The residues obtained after concentration of the reaction solution under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (89.2 mg, 62%). 
     (Method 3) To nitrobenzene (5 ml) and aluminum chloride (400 mg, 3 mmol), 4-methoxybenzoyl chloride (400 mg, 2.3 mmol) was added. After stirring for 30 min at room temperature, 2-(1-hydroxy-1-methyl-ethyl)-1H-indole-6-carbonitrile (Compound AA6, 200 mg, 1 mmol) was added followed by stirring at room temperature for 3 hr. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (127 mg, 40%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 1.71 (6H, s), 3.89 (3H, s), 7.07-7.09 (1H, m), 7.34 (1H, s), 7.58-7.60 (1H, m), 7.99 (1H, s), 8.14-8.16 (1H, m), 8.30-8.32 (1H, m), 12.32 (1H, br. s), 
     LCMS: m/z 317 [M+H] +   
     HPLC retention time: 2.56 min (analysis condition U) 
     Example 12 
     Compound A6 
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A5-2, 6.58 g, 20.8 mmol) was dissolved in pyridine hydrochloric acid salt (25.0 g), and stirred at 170° C. for 13 hr. The reaction mixture was partitioned in ethyl acetate (400 mL) and distilled water (400 mL), and the aqueous layer was extracted one more time with ethyl acetate (400 mL). The combined organic layer was washed twice with distilled water (100 mL) and once with saturated brine (100 mL) in order, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to yield a product, which was suspended and washed with a small amount of CPME to obtain the title compound as a colorless crystal (5.91 g, 93%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 1.73 (6H, s), 6.87-6.90 (1H, m), 7.11 (1H, s), 7.57-7.59 (1H, m), 7.97 (1H, s), 8.04-8.06 (1H, m), 8.29-8.31 (1H, m), 10.27 (1H, s), 12.66 (1H, br. s), 
     LCMS: m/z 303 [M+H] +   
     Example 13 
     Compound A7-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 30 mg, 0.099 mmol) was dissolved in THF (1 mL), added with 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (40 mg, 2 eq.), triphenylphosphine (52 mg, 2 eq.), and diisopropyl azodicarboxylate (43 μL, 2 eq.) in order, and stirred at room temperature for 4 hr. The reaction solution was poured to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (37 mg, 76%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 9.44 (1H, s), 8.77 (1H, d, J=7.8 Hz), 8.62 (1H, d, J=8.2 Hz), 8.00 (1H, s), 7.81 (1H, d, J=8.2 Hz), 7.34 (1H, s), 7.26 (1H, d, J=7.8 Hz), 4.85-4.93 (1H, m), 3.96-4.04 (2H, m), 3.60-3.70 (2H, m), 2.19-2.32 (2H, m), 1.89-2.15 (8H, m), 1.74 (9H, s) 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 4.09 min (analysis condition W) 
     Example 14 
     Compound A7-2 
     6,6-Dimethyl-11-oxo-8-[2-(2-oxo-imidazolidin-1-yl)-ethoxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 1-(2-hydroxy-ethyl)-imidazolidin-2-one. 
     LCMS: m/z 415 [M+H] +   
     HPLC retention time: 2.96 min (analysis condition W) 
     Example 15 
     Compound A7-3 
     [2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-carbamic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and (2-hydroxy-ethyl)-carbamic acid tert-butyl ester. 
     LCMS: m/z 346 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition W) 
     Example 16 
     Compound A7-4 
     6,6-Dimethyl-8-(2-methylsulfanyl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-methylthioethanol. 
     LCMS: m/z 451 [M+H] +   
     HPLC retention time: 4.23 min (analysis condition W) 
     Example 17 
     Compound A7-5 
     6,6-Dimethyl-8-(2-methylsulfanyl-ethoxy)-5-(2-methylsulfanyl-ethyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound A7-4. 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 3.75 min (analysis condition W) 
     Example 18 
     Compound A7-6 
     6,6-Dimethyl-11-oxo-8-(tetrahydro-pyran-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and tetrahydropyran-4-ol. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.72 (1H, br.s), 8.32 (1H, d, 8.5 Hz), 8.15 (1H, d, 8.5 Hz), 8.01 (1H, s), 7.61 (1H, d, 8.5 Hz), 7.38 (1H, s), 7.15 (1H, d, 8.5 Hz), 4.86-4.81 (1H, m), 3.93-3.88 (2H, m), 3.58-3.52 (2H, m), 2.06-2.00 (2H, m), 1.85 (6H, s), 1.69-1.60 (2H, m) 
     LCMS: m/z 387 [M+H] +   
     HPLC retention time: 3.47 min (analysis condition W) 
     Example 19 
     Compound A7-7 
     6,6-Dimethyl-11-oxo-8-(pyridin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and pyridin-4-yl-methanol. 
     LCMS: m/z 394 [M+H] +   
     HPLC retention time: 2.56 min (analysis condition W) 
     Example 20 
     Compound A7-8 
     8-(2-Methoxyethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-methoxyethanol. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 11.69 (1H, br. s), 8.27 (1H, d, 7.9 Hz), 8.10 (1H, d, 8.5 Hz), 7.95 (1H, s), 7.55 (1H, d, 7.9 Hz), 7.32 (1H, d, 2.4 Hz), 7.05 (1H, d, 8.5 Hz), 4.22 (2H, t, 4.3 Hz), 3.67 (2H, t, 4.3 Hz), 1.72 (6H, s) 
     LCMS: m/z 361 [M+H] +   
     HPLC retention time: 3.38 min (analysis condition W) 
     Example 21 
     Compound A7-9 
     8-[2-(2-Methoxyethoxy)ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-(2-methoxyethoxy)ethanol. 
     LCMS: m/z 405 [M+H] +   
     HPLC retention time: 3.32 min (analysis condition W) 
     Example 22 
     Compound A7-10 
     6,6-Dimethyl-8-(3-methyloxetan-3-ylmethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 3-chloromethyl-3-methyloxetane. 
     LCMS: m/z 387 [M+H] +   
     HPLC retention time: 2.23 min (analysis condition S) 
     Compound A7-11-1 
     [2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)ethyl]ethyl-carbamic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and ethyl-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester. 
     LCMS: m/z 474 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition U) 
     Example 24 
     Compound A7-11-2 
     8-(2-Ethylaminoethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A7-11-1. 
     LCMS: m/z 374 [M+H] +   
     HPLC retention time: 1.35 min (analysis condition U) 
     Example 25 
     Compound A7-12 
     8-(2-Hydroxyethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromo-ethanol. 
     LCMS: m/z 437 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition U) 
     Example 26 
     Compound A7-13-1 
     6,6-Dimethyl-11-oxo-8-(2-phenyl-[1,3]dioxan-5-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-phenyl-[1,3]dioxan-5-ol. 
     LCMS: m/z 465 [M+H] +   
     HPLC retention time: 4.10 min (analysis condition W) 
     Example 27 
     Compound A7-13-2 
     8-(2-Hydroxy-1-hydroxymethylethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Anhydrous ferric trichloride (56 mg, 5 eq.) was added to the dichloromethane (2 mL) suspension of 6,6-dimethyl-11-oxo-8-(2-phenyl-[1,3]dioxan-5-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A7-13-1, 13 mg, 0.028 mmol), and stirred at room temperature for 1 hr. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (7 mg, 46%). 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition W) 
     Example 28 
     Compound A7-14-1 
     8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester. 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 3.47 min (analysis condition Y) 
     Example 29 
     Compound A7-14-2 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the solution of THF and water (4:1, 1 mL) of 8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A14-1, 30 mg, 0.07 mmol), camphor sulfonic acid (36 mg, 0.14 mmol) was added at room temperature. After stirring at room temperature for 38 hr, the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (white solid, 28 mg, 72%). 
       1 H-NMR (300 MHz, DMSO-d 6 ) σppm; 12.7 (s, 1H), 8.31 (d, 1H, J=8.01 Hz), 8.15 (d, 1H, J=8.77 Hz), 8.00 (s, 1H), 7.60 (d, 1H, J=8.01 Hz), 7.12 (s, 1H), 7.09 (d, 1H, J=8.77 Hz), 4.46 (m, 1H), 4.15 (m, 3H), 3.78 (m, 1H), 1.76 (s, 6H), 1.38 (s, 3H), 1.32 (s, 3H) 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition U) 
     Example 30 
     Compound A7-14-3 
     8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared as a crude product from Compound A7-14-1. 
     Example 31 
     Compound A7-14-4 
     8-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A7-14-3 (303 mg, 98%). 
     LCMS: m/z 484 [M+H] +   
     HPLC retention time: 2.08 min (analysis condition D) 
     Example 32 
     Compound A7-15-1 
     8-[(4R,5S)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol. 
     LCMS: m/z 516 [M+H] +   
     HPLC retention time: 3.97 min (analysis condition Y) 
     Example 33 
     Compound A7-15-2 
     6,6-Dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A7-15-1. 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 1.73 min (analysis condition U) 
     Example 34 
     Compound A7-16 
     6,6-Dimethyl-8-(1-methyl-piperidin-4-yloxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 1-methylpiperidin-4-ol. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.75 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.14 (1H, d, J=9.8 Hz), 8.00 (1H, s), 7.60 (1H, d, J=7.9 Hz), 7.34 (1H, s), 7.11 (1H, d, J=9.1 Hz), 4.62 (1H, m), 2.64 (2H, m), 2.23 (2H, m), 2.21 (s, 3H), 1.99 (2H, m), 1.77 (s, 6H), 1.73 (2H, m). 
     LCMS: m/z 400 [M+H] +   
     HPLC retention time: 1.42 min (analysis condition S) 
     Example 35 
     Compound A7-17 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 25 mg, 0.083 mmol) was dissolved in N,N-dimethylacetamide (1 mL), added with 2-chloroethyldiethylamine (16 mg, 1.1 eq.) and cesium carbonate (54 mg, 2 eq.) in order and stirred at 100° C. for 4 hr. The reaction solution was poured over water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by amino silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (11 mg, 32%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.32 (1H, d, J=8.2 Hz), 8.15 (1H, d, J=8.7 Hz), 8.01 (1H, s), 7.61 (1H, d, J=8.2 Hz), 7.35 (1H, d, J=1.8 Hz), 7.09 (1H, dd, J=8.7, 1.8 Hz), 4.19 (2H, t, J=5.9 Hz), 2.83 (2H, t, J=5.9 Hz), 2.58 (4H, q, J=7.0 Hz), 1.78 (6H, s), 1.00 (6H, t, J=7.0 Hz) 
     LCMS: m/z 402 [M+H] +   
     HPLC retention time: 2.52 min (analysis condition W) 
     Example 36 
     Compound A7-18 
     N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-acetamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-chloroethylacetamide. 
     LCMS: m/z 388 [M+H] +   
     HPLC retention time: 2.91 min (analysis condition W) 
     Example 37 
     Compound A7-19 
     [2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-carbamic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and ethyl-2-chloroethylcarbamate. 
     LCMS: m/z 418 [M+H] +   
     HPLC retention time: 3.35 min (analysis condition W) 
     Example 38 
     Compound A7-20 
     [2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-urea 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-chloroethylurea. 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition W) 
     Example 39 
     Compound A7-21 
     6,6-Dimethyl-8-(oxetan-3-yloxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and toluene-4-sulfonic acid oxetan-3-yl ester. 
     LCMS: m/z 359 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition S) 
     Example 40 
     Compound A7-22 
     6,6-Dimethyl-11-oxo-8-(pyrimidin-2-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromopyrimidine. 
     LCMS: m/z 381 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition S) 
     Example 41 
     Compound A7-23 
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl acetate ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 3-chloro-propionic acid ethyl ester. 
     LCMS: m/z 389 [M+H] +   
     HPLC retention time: 3.37 min (analysis condition U) 
     Example 42 
     Compound A7-24 
     8-(2-Bromo-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-bromoethanol. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.75 (1H, br.s), 8.32 (1H, d, J=8.2 Hz), 8.17 (1H, d, J=8.6 Hz), 8.01 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.40 (1H, d, J=2.2 Hz), 7.12 (1H, dd, J=8.6, 2.2 Hz), 4.50 (2H, t, J=5.3 Hz), 3.88 (2H, t, J=5.3 Hz), 1.77 (6H, s). 
     LCMS: m/z 409, 411 [M+H] +   
     HPLC retention time: 2.48 min (analysis condition S) 
     Example 43 
     Compound A7-25 
     6,6-Dimethyl-11-oxo-8-(piperidin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloric acid salt 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 3-cyano-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A6, 85 mg, 0.28 mmol) and triphenylphosphine (150 mg, 2 eq.) were added with THF (2 ml), and then further added dropwise with 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (120 mg, 2 eq.) and 2.19 N toluene solution of diethyl azodicarboxylic acid (0.26 mL, 2 eq.). The resultant was stirred at room temperature for 12 hr under nitrogen atmosphere. The residues obtained after concentrating the reaction solution under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (white powder, 120 mg). 
     To the resulting compound, 4 N hydrochloric acid and dioxane solution was added under cooling. After stirring at room temperature for 2 hr, the solvent was removed under nitrogen stream. Then, the residues were washed with diethyl ether and then subjected to azeotropic treatment with toluene, followed by drying under vacuum and filtration to obtain the title compound (79 mg). 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition C) 
     Example 44 
     Compound A8-1 
     6,6-Dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     THF (0.5 mL) and TFA (0.5 mL) were added to 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound A7-1, 35 mg, 0.072 mmol), and the mixture was stirred at room temperature until Compound A7-1 disappears. The reaction solution was concentrated under reduced pressure and the residue was desalinated by using anion exchanger PL StratoSpheres (trademark) PL-HCO3 MP to obtain the title compound (37 mg, 76%). 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.38 (1H, d, J=7.9 Hz), 8.24 (1H, d, J=8.5 Hz), 7.85 (1H, s), 7.53 (1H, d, J=7.9 Hz), 7.27 (1H, s), 7.09 (1H, d, J=8.5 Hz), 4.67-4.76 (1H, m), 3.07-3.20 (2H, m), 2.77-2.87 (2H, m), 2.03-2.15 (2H, m), 1.80 (6H, s), 1.69-1.77 (2H, m) 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 2.51 min (analysis condition W) 
     Example 45 
     Compound A8-2 
     8-(2-Amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A7-3. 
     LCMS: m/z 346 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition W) 
     Example 46 
     Compound A8-3 
     8-(2-Methanesulfonyl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound A7-5. 
     LCMS: m/z 409 [M+H] +   
     HPLC retention time: 3.13 min (analysis condition W) 
     Example 47 
     Compound A8-4 
     8-(2-Methanesulfinyl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound A8-3. 
     LCMS: m/z 393 [M+H] +   
     HPLC retention time: 2.87 min (analysis condition W) 
     Example 48 
     Compound A8-5 
     5,6,6-Trimethyl-11-oxo-8-(tetrahydro-pyran-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound A7-6. 
     LCMS: m/z 401 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition S) 
     Example 49 
     Compound A8-6-1 
     2-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A5-2, 50 mg, 0.158 mmol) was dissolved in CH 3 CN (1 mL), added with NBS (56 mg, 2 eq.), and stirred at 80° C. overnight. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with MeOH and the solid remained after dissolution was filtered to obtain the target compound (yellow powder, 20 mg, 38%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.92 (1H, s), 8.50 (1H, s), 8.16 (1H, d, J=8.5 Hz), 8.14 (1H, s), 7.36 (1H, d, J=2.4 Hz), 7.11 (1H, dd, J=8.5, 2.4 Hz), 3.92 (3H, s), 1.78 (6H, s). 
     LCMS: m/z 395, 397 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition S) 
     Example 50 
     Compound A8-6-2 
     2-Bromo-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound A8-6-1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.46 (1H, s), 8.10 (1H, s), 8.05 (1H, d, J=8.6 Hz), 7.13 (1H, d, J=2.1 Hz), 6.89 (1H, dd, J=8.5, 2.1 Hz), 1.71 (6H, s). 
     LCMS: m/z 381,383 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition S) 
     Example 51 
     Compound A8-6-3 
     2-Bromo-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-6-2. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.53 (1H, d, J=0.5 Hz), 8.20 (1H, d, J=8.7 Hz), 7.88 (1H, d, J=0.5 Hz), 7.28 (1H, d, J=2.3 Hz), 7.05 (1H, dd, J=8.9, 2.5 Hz), 4.24 (2H, t, J=5.7 Hz), 2.96 (2H, t, J=5.7 Hz), 2.70 (4H, q, J=7.1 Hz), 1.79 (6H, s), 1.12 (6H, t, J=7.2 Hz). 
     LCMS: m/z 480, 482 [M+H] +   
     HPLC retention time: 1.73 min (analysis condition S) 
     Example 52 
     Compound A8-7 
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid 
     
       
         
         
             
             
         
       
     
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl acetate ester (Compound A7-23, 180 mg, 0.464 mmol) and potassium hydroxide (130 mg, 2.32 mmol) were dissolved in THF (10 ml) and water (1.8 mL), and stirred at 70° C. for 2 hr. After cooling to room temperature, the mixture was extracted with dichloromethane. Water layer ( ) was adjusted to be acidic by using 1 N hydrochloric acid, and the precipitated solid was filtered and washed several times with water to obtain the title compound (white solid, 130 mg, 78%). 
       1 H-NMR (300 MHz, DMSO) σppm 13.09 (s, 1H), 8.31 (d, 1H, J=8.1 Hz), 8.11 (d, 1H, J=8.4 Hz), 8.01 (s, 1H), 7.58 (d, 1H, J=7.8 Hz), 7.25 (d, 1H, J=2.1 Hz), 6.97 (d, 1H, J=8.4 Hz), 4.51 (s, 2H), 1.73 (s, 6H) 
     LCMS: m/z 361 [M+H] +   
     HPLC retention time: 2.97 min (analysis condition U) 
     Example 53 
     Compound A8-8 
     6,6-Dimethyl-8-(2-morpholin-4-yl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and morpholine. 
       1 H-NMR (500 MHz, CD 3 OD+CDCl 3 ) σ ppm; 8.4 (d, 1H, J=8.2 Hz), 8.3 (d, 1H, J=8.7 Hz), 7.8 (s, 1H), 7.5 (dd, 1H, J=1.1 Hz, J=8.2 Hz), 7.2 (d, 1H, J=2.3 Hz), 7.0 (dd, 1H, J=2.2 Hz, J=8.7 Hz), 4.2 (t, 2H, J=5.3 Hz), 3.7 (t, 4H, J=4.5 Hz), 2.9 (t, 2H, J=5.3 Hz), 2.6 (t, 4H, J=4.5 Hz), 1.8 (s, 6H) 
     LCMS: m/z 416 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition U) 
     Example 54 
     Compound A8-9 
     8-[2-(1,1-Dioxothiomorpholino)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and thiomorpholine-1,1-dioxide. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.72 (1H, s), 8.31 (1H, d, 8.5 Hz), 8.15 (1H, d, 8.5 Hz), 8.00 (1H, s), 7.60 (1H, d, 8.5 Hz), 7.36 (1H, d, 1.8 Hz), 7.10 (1H, dd, 1.8, 8.5), 4.25 (2H, t, 5.5 Hz), 3.06-3.33 (8H, m), 2.97 (2H, t, 5.5), 1.77 (6H, s) 
     LCMS: m/z 464 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition W) 
     Example 55 
     Compound A8-10 
     8-(2-Tert-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and tert-butylamine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.71 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.15 (1H, d, 9.1 Hz), 8.07 (1 d, 1.8 Hz), 7.60 (1H, dd, 1.8, 7.9 Hz), 7.35 (1H, d, 2.4 Hz), 7.09 (1H, dd, 2.4, 9.1 Hz), 4.16 (2H, t, 6.1 Hz), 2.91 (2H, t, 6.1 Hz), 1.77 (6H, s), 1.08 (9H, s) 
     LCMS: m/z 402 [M+H] +   
     HPLC retention time: 2.55 min (analysis condition W) 
     Example 56 
     Compound A8-11 
     8-(2-Sec-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and sec-butylamine. 
     LCMS: m/z 402 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 57 
     Compound A8-12 
     8-[2-(2-Hydroxy-1,1-dimethyl-ethylamino)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and 2-amino-2-methyl-propan-1-ol. 
       1 H-NMR (300 MHz, DMSO-d6) σppm; 12.65 (brs, 1H), 8.31 (d, 1H, J=8.0 Hz), 8.15 (d, 1H, J=8.8 Hz), 7.99 (s, 1H), 7.59 (d, 1H, J=8.0 Hz), 7.34 (d, 1H, J=2.3 Hz), 7.08 (dd, 1H, J=2.2 Hz, J=8.8 Hz), 4.58 (brs, 1H), 4.16 (t, 2H, J=5.7 Hz), 3.20 (s, 2H), 2.88 (t, 2H, J=5.7 Hz), 1.76 (s, 6H), 0.97 (s, 6H) 
     LCMS: m/z 418 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition U) 
     Example 58 
     Compound A8-13 
     8-[2-(4-Ethyl-piperazin-1-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and 1-ethyl-piperazine. 
     LCMS: m/z 443 [M+H] +   
     HPLC retention time: 1.68 min (analysis condition U) 
     Example 59 
     Compound A8-14 
     8-(2-Imidazol-1-yl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-imidazol-1-yl-ethanol. 
       1 H-NMR (300 MHz, DMSO-d 6 ) σ ppm; 12.71 (s, 1H), 8.31 (d, 1H, J=8.3 Hz), 8.14 (d, 1H, J=8.8 Hz), 7.99 (s, 1H), 7.73 (s, 1H), 7.60 (d, 1H, J=8.3 Hz), 7.34 (s, 1H), 7.29 (s, 1H), 7.09 (d, 1H, J=8.8 Hz), 6.91 (s, 1H), 4.20 (s, 4H), 1.76 (s, 6H) 
     LCMS: m/z 387 [M+H] +   
     HPLC retention time: 1.77 min (analysis condition U) 
     Example 60 
     Compound A8-15 
     8-{2-[Bis-(2-hydroxy-ethyl)-amino]-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and 2-(2-hydroxy-ethylamino)-ethanol. 
     LCMS: m/z 434 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition U) 
     Example 61 
     Compound A8-16 
     1-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-piperidine-4-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and piperidine-4-carboxylic acid amide. 
     LCMS: m/z 457 [M+H] +   
     HPLC retention time: 1.28 min (analysis condition S) 
     Example 62 
     Compound A8-17 
     6,6-Dimethyl-11-oxo-8-[2-(3-oxo-piperazin-1-yl)-ethoxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To DMF solution (5 mL) of 8-(2-bromo-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A7-24, 30 mg, 0.07 mmol), piperazin-2-one (44.9 mg, 0.35 mmol) and N,N-diisopropylethylamine(0.061 mL, 0.35 mmol) were added at room temperature and stirred at 80° C. for 18 hr. After cooling to room temperature, the mixture was extracted with ethyl acetate washed with saturated brine. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by preparative TLC (dichloromethane/methanol) to obtain the title compound (white solid, 24 mg, 80%). 
       1 H-NMR (300 MHz, DMSO-d6) σppm; 12.71 (s, 1H), 8.32 (d, 1H, J=8.4 Hz), 8.15 (d, 1H, J=8.8 Hz), 8.00 (s, 1H), 7.75 (s, 1H), 7.60 (d, 1H, J=8.4 Hz), 7.37 (d, 1H, J=2.3 Hz), 7.09 (dd, 1H, J=2.3 Hz, J=8.8 Hz), 4.27 (t, 2H, J=5.7 Hz), 3.19 (m, 2H), 3.08 (s, 2H), 2.83 (t, 2H, J=5.7 Hz), 2.70 (t, 2H, J=5.7 Hz), 1.8 (s, 6H) 
     LCMS: m/z 429 [M+H] +   
     HPLC retention time: 1.29 min (analysis condition S) 
     Example 63 
     Compound A8-18 
     Morpholine-4-sulfonic acid[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-amide 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound C1-2. 
     LCMS: m/z 495 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition S) 
     Example 64 
     Compound A8-19 
     4-Methyl-piperazine-1-sulfonic acid[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-amide 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound C1-4. 
       1 H-NMR (300 MHz, DMSO-d6) δ: 1.77 (6H, s), 2.16 (3H, s), 2.34 (4H, m), 3.08 (4H, m), 3.35 (2H, m), 4.19 (2H, t, 5.34 Hz), 7.09 (1H, dd, 8.77 Hz, 2.99 Hz), 7.37 (1H, bs, 1.91 Hz), 7.59 (2H, m), 8.01 (1H, s), 8.16 (1H, d, 8.40 Hz), 8.32 (1H, d, 8.01 Hz), 12.7 (1H, s). 
     LCMS: m/z 501 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 65 
     Compound A8-20 
     6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6,6-Dimethyl-11-oxo-8-(piperidin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloric acid salt (Compound A7-25, 30 mg, 0.075 mmol) and oxetan-3-one (38 mg, 7 eq.) were dissolved in acetic acid (0.2 ml), THF (1 ml) and methanol (1 ml), added with sodium cyanoborohydride (33 mg, 7 eq.) at room temperature, and stirred overnight. The reaction solution was added with water, and then extracted with ethyl acetate. The solution was dried over sodium sulfate and the solvent was removed under vacuum and the resulting residues were purified by preparative TLC (chloroform: 2 N ammonia methanol=9:1) to obtain the target compound (15 mg). 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 2.78 min (analysis condition C) 
     Example 66 
     Compound A8-21 
     6,6-Dimethyl-8-[2-(1-oxetan-3-yl-piperidin-4-yl)-ethoxy]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-25, and Compound A8-20, the title compound was prepared from Compound A6 and 4-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (15 mg). 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition C) 
     Example 67 
     Compound A9-1 
     N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Trifluoroacetic acid salt of 8-(2-amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A8-2, 19 mg, 0.044 mmol) was suspended in dichloromethane (0.5 mL), added with diisopropylethylamine (0.0157 mL, 2 eq.) and methanesulfonyl chloride (0.0034 mL, 1 eq.), and then stirred at room temperature for 2 hr. The reaction solution was added to water, and then extracted with dichloromethane. After washing with saturated brine, the organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were separated by silica gel preparative TLC (ethyl acetate 100%) to obtain the target compound (5.5 mg, 29%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.47 (1H, d, J=8.2 Hz), 8.32 (1H, d, J=8.7 Hz), 8.16 (1H, s), 7.76 (1H, d, J=8.2 Hz), 7.53-7.46 (2H, m), 7.26 (1H, d, J=8.7 Hz), 4.39-4.33 (2H, m), 3.58-3.51 (2H, m), 3.12 (3H, s), 1.93 (6H, s) 
     LCMS: m/z 424 [M+H] +   
     HPLC retention time: 3.10 min (analysis condition W) 
     Example 68 
     Compound A9-2 
     N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-2,2,2-trifluoro-acetamide 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound A9-1. 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 3.45 min (analysis condition W) 
     Example 69 
     Compound A9-3-1 
     8-{2-(Tert-butyloxycarbonylaminosulfonyl)amino-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Trifluoroacetic acid salt of 8-(2-amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A8-2, 20 mg, 0.044 mmol) was dissolved in pyridine (0.5 mL), added with N-(tert-butoxycarbonyl)-N-[4-(dimethyl azaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (13.5 mg, 1 eq.), and then stirred at room temperature for 14 hr. The reaction solution was added to water, and then extracted with ethyl acetate. After washing with saturated brine, the organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were separated by silica gel preparative TLC(ethyl acetate) to obtain the title compound (16.1 mg, 68%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.74 (1H, s), 10.94 (1H, s), 8.33 (1H, d, J=8.5 Hz), 8.16 (1H, d, J=9.1 Hz), 8.02 (1H, s), 7.84 (1H, br. s), 7.62 (1H, d, J=7.9 Hz), 7.36 (1H, s), 7.10 (1H, d, J=7.9 Hz). 4.24-4.18 (2H, in), 1.78 (6H, s), 1.32 (9H, s) 
     LCMS: m/z 525 [M+H] +   
     HPLC retention time: 3.48 min (analysis condition W) 
     Example 70 
     Compound A9-3-2 
     8-{2-(Methylaminosulfonyl)amino-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A9-3-1. 
     LCMS: m/z 425 [M+H] +   
     HPLC retention time: 2.95 min (analysis condition W) 
     Example 71 
     Compound A9-4 
     8-(1-Methanesulfonyl-piperidin-4-yloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and methanesulfonyl chloride. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.72 (1H, s), 8.30 (1H, d, J=8.5 Hz), 8.14 (1H, d, J=8.5 Hz), 8.00 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.38 (1H, s), 7.13 (1H, d, J=8.5 Hz), 4.81 (1H, s), 3.39-3.38 (2H, m), 3.19-3.13 (2H, m), 2.93 (3H, s), 2.11-2.04 (2H, m), 1.83-1.75 (8H, m). 
     LCMS: m/z 464 [M+H] +   
     HPLC retention time: 3.41 min (analysis condition U) 
     Example 72 
     Compound A9-5 
     8-[1-(2-Methoxy-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound A8-1 and 1-bromo-2-methoxy-ethane. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 8.48-8.53 (1H, m), 8.32-8.38 (1H, m), 7.74-7.77 (1H, m), 7.50-7.55 (1H, m), 7.07-7.10 (1H, m), 6.95-7.00 (1H, m), 4.43-4.51 (1H, m), 3.53 (2H, t, J=5.6 Hz), 3.36 (3H, s), 2.77-2.87 (2H, m), 2.62 (2H, t, J=5.6 Hz), 2.35-2.47 (2H, m), 2.02-2.12 (2H, m), 1.78-1.95 (2H, m), 1.82 (6H, s). 
     LCMS: m/z 444 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition U) 
     Example 73 
     Compound A9-6-2 
     8-[1-(2-Hydroxy-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and (2-bromoethoxy)-tert-butyldimethylsilane, followed by treatment with tetrabutylammonium fluoride. 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Example 74 
     Compound A9-7 
     8-[1-(2-Fluoro-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and methanesulfonic acid 2-fluoroethyl ester. 
       1 H-NMR (300 MHz, DMSO-d6) δ: 1.67 (2H, m), 1.76 (6H, s), 2.01 (2H, m), 2.37 (2H, t, 11.0 Hz), 2.61 (1H, t, 4.20 Hz), 2.70 (1H, t, 4.58), 2.78 (2H, m), 4.46 (1H, t, 4.58 Hz), 4.62 (2H, t, 5.34 Hz), 7.10 (1H, dd, 9.16 Hz, 2.29 Hz), 7.34 (1H, bs, 1.53 Hz), 7.60 (1H, dd, 8.40 Hz, 1.53 Hz), 7.99 (1H, s), 8.13 (1H, d, 8.39 Hz), 8.30 (1H, d, 8.39 Hz), 12.7 (1H, s). 
     LCMS: m/z 432 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 75 
     Compound A9-8 
     8-(1-Acetyl-piperidin-4-yloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and acetyl chloride. 
     LCMS: m/z 428 [M+H] +   
     HPLC retention time: 1.91 min (analysis condition S) 
     Example 76 
     Compound A9-9 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromo-acetamide. 
     LCMS: m/z 360 [M+H] +   
     HPLC retention time: 2.83 min (analysis condition U) 
     Example 77 
     Compound A9-10 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-methyl-acetamide 
     
       
         
         
             
             
         
       
     
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.0838 mmol), methylamine hydrochloric acid salt (28.1 mg, 0.417 mmol), EDC (32 mg, 0.167 mmol) and HOBT (0.023 mg, 0.167 mmol) were dissolved in DMF (1 mL), and added with diisopropylethylamine (0.145 mL, 0.833 mmol) at room temperature. After stirring at room temperature for 18 hr, water was added and the extraction was carried out with ethyl acetate. After washing with saturated brine, the organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were dissolved in dichloromethane, added with diethyl ether, and the precipitated title compound was obtained (white solid, 19.7 mg, 63%). 
       1 H-NMR (300 MHz, DMSO) a ppm 12.73 (s, 1H), 8.33 (d, 1H, J=8.1 Hz), 8.17 (d, 1H, J=8.7 Hz), 8.13 (s, 1H), 8.00 (s, 1H), 7.62 (d, 1H, J=8.1 Hz), 7.39 (d, 1H, J=2.4 Hz), 7.11 (dd, 1H, J=8.7 Hz, 2.4 Hz), 4.64 (s, 2H), 3.17 (d, 1H, J=5.4 Hz), 2.69 (d, 1H, J=4.5 Hz), 1.76 (s, 6H) 
     LCMS: m/z 374 [M+H] +   
     HPLC retention time: 2.43 min (analysis condition U) 
     Example 78 
     Compound A9-11 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-acetamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound A8-7 and C-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methylamine. 
     LCMS: m/z 474 [M+H] +   
     HPLC retention time: 2.20 min (analysis condition U) 
     Example 79 
     Compound A9-12 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2,3-dihydroxy-propyl)-acetamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A9-11. 
     LCMS: m/z 434 [M+H] +   
     HPLC retention time: 1.72 min (analysis condition U) 
     Example 80 
     Compound A9-13 
     2-Methyl-acrylic acid 2-[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetylamino]-ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound A8-7 and 2-methyl-acrylic acid 2-amino-ethyl ester. 
     LCMS: m/z 472 [M+H] +   
     HPLC retention time: 3.30 min (analysis condition U) 
     Example 81 
     Compound A9-14 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-hydroxy-ethyl)-acetamide 
     
       
         
         
             
             
         
       
     
     2-Methyl-acrylic acid 2-[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetylamino]-ethyl ester (Compound A9-13, 40 mg, 0.085 mmol) was dissolved in a mixture solvent of methanol (2 mL) and water (2 mL), added with potassium hydroxide (48 mg, 0.85 mmol), and then stirred at room temperature for 18 hr. After the neutralization with 1 N hydrochloric acid, the reaction solution was concentrated under reduced pressure. The resulting residues were purified by amino silica gel to obtain the title compound (white solid, 8.9 mg, 26%). 
       1 H-NMR (300 MHz, DMSO) a ppm 12.75 (s, 1H), 8.32 (d, 1H, J=8.1 Hz), 8.17-8.13 (m, 2 Hz), 7.99 (s, 1H), 7.60 (d, 1H, J=8.1 Hz), 7.38 (d, 1H, J=1.8 Hz), 7.11 (dd, 1H, J=2.1 Hz, 8.7 Hz), 4.72 (t, 1H, J=5.7 Hz), 4.65 (s, 1H), 3.48 (dd, 2H, J=12.0 Hz, 6.0 Hz), 3.26 (dd, 2H, J=12.0 Hz, 6.0 Hz), 1.76 (s, 6H) 
     LCMS: m/z 404 [M+H] +   
     HPLC retention time: 2.83 min (analysis condition U) 
     Example 82 
     Compound A9-15-1 
     4-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), piperazine-1-carboxylic acid tert-butyl ester (31 mg, 2 eq.), and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (20 mg). 
     LCMS: m/z 527, 471, 427[M−H] −   
     HPLC retention time: 2.77 min (analysis condition C) 
     Example 83 
     Compound A9-15-2 
     6,6-Dimethyl-11-oxo-8-(2-oxo-2-piperazin-1-yl-ethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloric acid salt 
     
       
         
         
             
             
         
       
     
     4-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester (Compound A9-15-1, 20 mg) was added with 4 N hydrochloric acid and dioxane solution (1 ml), and stirred in an water bath at 10° C. for 4 hr. Water was added to the reaction solution and the resulting precipitates were filtered and dried to obtain the title compound (15 mg, white powder). 
     LCMS: m/z 429 [M+H] +   
     HPLC retention time: 0.81 min (analysis condition I) 
     Example 84 
     Compound A9-16 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-cyano-ethyl)-acetamide 
     
       
         
         
             
             
         
       
     
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), 3-aminopropionitrile (12 mg, 2 eq.) and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (23 mg). 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition C) 
     Example 85 
     Compound A9-17 
     2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-cyano-ethyl)-N-methyl-acetamide 
     
       
         
         
             
             
         
       
     
     (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), N-methyl-3-aminopropionitrile (14 mg, 2 eq.) and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (7 mg). 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 2.33 min (analysis condition C) 
     Example 86 
     Compound A10 
     8-(Tert-butyl-dimethyl-silanyloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The DMF solution of 8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 100 mg, 0.331 mmol), imidazole (67.5 mg, 3 eq.) and tert-butylchlorodimethylsilane (92.4 mg, 1.5 eq.) was stirred overnight at room temperature. To the reaction solution, saturated aqueous solution of sodium hydrogen carbonate was added followed by extraction with tert-butylmethyl ether. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white solid, 170 mg, 100%). 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 3.38 min (analysis condition S) 
     Example 87 
     Compound A10-1 
     8-Methoxy-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the THF solution of triphenylphosphine (260 mg, 3 eq.), azodicarboxylic acid diisopropyl ester (0.195 ml, 3 eq.) was added and the mixture was stirred at room temperature for 1 hr. Thereafter, 8-(tert-butyldimethylsilanyloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A10, 138 mg, 0.331 mmol) and methanol (1 ml) were added and stirred overnight. The reaction solution was purified by HPLC to obtain the target compound (44.8 mg, 41%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.44 (1H, d, J=8.1 Hz), 8.33 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.66 (1H, dd, J=8.2, 1.1 Hz), 7.39 (1H, d, J=2.3 Hz), 7.09 (1H, dd, J=8.7, 2.3 Hz), 4.17 (3H, s), 3.92 (3H, s), 1.88 (6H, s). 
     LCMS: m/z 331 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition S) 
     Example 88 
     Compound A10-2 
     8-(1-Methanesulfonyl-piperidin-4-yloxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared from Compound A9-4. 
     LCMS: m/z 478 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition U) 
     Example 89 
     Compound B1 
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 550 mg, 0.189 mmol) was dissolved in pyridine (18 mL), added with anhydrous trifluoromethanesulfonic acid (0.758 ml, 3 eq.), and stirred at room temperature for 30 min. The reaction solution was added to water and then extracted with dichloromethane. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white powder, 641 mg, 81%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.89 (1H, br. s), 8.36 (1H, d, J=8.8 Hz), 8.31 (1H, dd, J=8.1, 0.7 Hz), 8.11 (1H, d, J=2.3 Hz), 8.04 (1H, dd, J=1.5, 0.7 Hz), 7.65-7.60 (2H, m). 1.76 (6H, s) 
     LCMS: m/z 435 [M+H] +   
     HPLC retention time: 3.10 min (analysis condition U) 
     Example 90 
     Compound B2-1 
     8-(4-Isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 40 mg, 0.0921 mmol) was dissolved in NMP (1 ml) and added with 1-isopropylpiperazine (236 mg, 20 eq.). The mixture was stirred at 120° C. for 3 hr. After cooling to room temperature, purification was carried out by HPLC to obtain the target compound (white powder, 12.8 mg, 34%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, 8.1 Hz), 8.03 (1H, d, 8.6 Hz), 7.98 (1H, s), 7.56 (1H, d, 8.6 Hz), 7.21 (1H, s), 7.04 (1H, d, 9.1 Hz), 3.40-3.37 (4H, m), 2.73-2.65 (1H, m), 2.61-2.58 (4H, m), 1.75 (6H, s), 1.02 (6H, d, 6.6 Hz) 
     LCMS: m/z 413 [M+H] +   
     Example 91 
     Compound B2-2 
     8-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and N-(2-hydroxyethyl)piperazine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, 8.1 Hz), 8.03 (1H, d, 8.7 Hz), 7.99 (1H, s), 7.58 (1H, d, 7.9 Hz), 7.21 (1H, s), 7.04 (1H, d, 8.7 Hz), 4.50-4.46 (1H, br m), 3.59-3.53 (2H, m), 3.39-3.35 (4H, m), 2.59-2.56 (4H, m), 2.45 (2H, t, 6.1 Hz), 1.76 (6H, s) 
     LCMS: m/z 415 [M+H] +   
     HPLC retention time: 1.27 min (analysis condition S) 
     Example 92 
     Compound B2-3 
     6,6-Dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and morpholine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.62 (1H, br. s), 8.29 (1H, d, 8.2 Hz), 8.04 (1H, d, 9.0 Hz), 7.96 (1H, s), 7.56 (1H, d, 8.2 Hz), 7.22 (1H, s), 7.04 (1H, d, 9.0 Hz), 3.77-3.75 (4H, m), 3.35-3.30 (4H, m), 1.74 (6H, s) 
     LCMS: m/z 372 [M+H] +   
     HPLC retention time: 2.45 min (analysis condition U) 
     Example 93 
     Compound B2-4 
     6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 4-pyrrolidin-1-yl-piperidine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, 8.1 Hz), 8.01 (1H, d, 8.7 Hz), 7.97 (1H, s), 7.56 (1H, d, 8.6 Hz), 7.20 (1H, s), 3.94-3.90 (2H, m), 3.30-3.28 (4H, m), 2.95 (2H, t, 11.8 Hz), 2.24-2.20 (1H, m), 1.95-1.91 (2H, m), 1.75 (6H, s), 1.70-1.66 (4H, m), 1.54-1.52 (2H, m) 
     LCMS: m/z 439 [M+H] +   
     Example 94 
     Compound B2-5-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperazine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 471 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition S) 
     Example 95 
     Compound B2-5-2 
     6,6-Dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-5-1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.32 (1H, d, 8.5 Hz), 8.03 (1H, d, 9.1 Hz), 7.99 (1H, s), 7.59 (1H, dd, 8.2, 1.5 Hz), 7.20 (1H, d, 2.4 Hz), 7.04 (1H, dd, 8.8, 2.1 Hz), 3.32-3.30 (4H, m), 2.88-2.87 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 371 [M+H] +   
     Example 96 
     Compound B2-6 
     6,6-Dimethyl-11-oxo-8-piperidin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperidine. 
     LCMS: m/z 370 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition U) 
     Example 97 
     Compound B2-7-1 
     8-(4-Hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperidin-4-ol. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, 8.1 Hz), 8.01 (1H, d, 8.7 Hz), 7.97 (1H, s), 7.56 (1H, d, 7.7 Hz), 7.19 (1H, s), 7.04 (1H, d, 10.6 Hz), 4.76-4.71 (1H, br m), 3.81-3.75 (3H, m), 3.08 (2H, t, 10.2 Hz), 1.86-1.82 (2H, m), 1.75 (6H, s), 1.49-1.42 (2H, m) 
     LCMS: m/z 386 [M+H] +   
     Example 98 
     Compound B2-7-2 
     6,6-Dimethyl-11-oxo-8-(4-oxo-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-(4-Hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-7-1, 210 mg, 0.545 mmol), was dissolved in the DCM (2 mL) and DMF (0.6 mL) mixture solvent, added with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3 (1H)-one (300 mg, 1.3 eq.), and the mixture was stirred at room temperature for 2 hr. To the reaction solution, 0.25 mol/L aqueous solution of sodium thiosulfate, saturated sodium bicarbonate solution and CPME were added followed by further stirring at room temperature for 1 hr. The reaction solution was filtered and the filtrate was subjected to liquid separation. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellowish white powder, 109 mg, 52%). 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition U) 
     Example 99 
     Compound B2-8 
     8-(4-Methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 1-methanesulfonylpiperazine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.66 (1H, br.s), 8.31 (1H, d, J=8.2 Hz), 8.06 (1H, d, J=8.7 Hz), 7.99 (1H, s), 7.59 (1H, d, J=8.2 Hz), 7.30 (1H, d, J=1.8 Hz), 7.09 (1H, dd, J=8.7, 1.8 Hz), 3.53 (4H, t, J=4.8 Hz), 3.27 (4H, t, J=4.8 Hz), 2.94 (3H, s), 1.77 (6H, s). 
     LCMS: m/z 449 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition S) 
     Example 100 
     Compound B2-9 
     8-(3-Methanesulfonyl-pyrrolidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 3-methanesulfonylpyrrolidine. 
     LCMS: m/z 434 [M+H] +   
     HPLC retention time: 1.83 min (analysis condition S) 
     Example 101 
     Compound B2-10 
     8-(1,1-Dioxothiomorpholino)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 30 mg, 0.069 mmol) was dissolved in 1,4-dioxane (1 mL), added with thiomorpholine 1,1-dioxide (19 mg, 2 eq.), Pd 2  (dba) 3  (6.3 mg, 0.1 eq.), BINAP (8.6 mg, 0.2 eq.) and K 3 PO 4  (29 mg, 2 eq.), and stirred at 100° C. overnight. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white powder, 2.1 mg, 7%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=8.6 Hz), 8.07 (1H, d, J=8.9 Hz), 8.00 (1H, s), 7.55 (1H, dd, J=8.5, 1.7 Hz), 7.34 (1H, d, J=2.0 Hz), 7.15 (1H, dd, J=9.1, 2.7 Hz), 4.01 (4H, s), 3.16 (4H, s), 1.77 (6H, s). 
     LCMS: m/z 420 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition S) 
     Example 102 
     Compound B2-11 
     8-(4-Cyclopentyl-2-oxo-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound B1 and 4-cyclopentylpiperazin-2-one. 
     LCMS: m/z 453 [M+H] +   
     HPLC retention time: 1.30 min (analysis condition S) 
     Example 103 
     Compound B2-12 
     6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 4-piperidin-4-yl morpholine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.73 (1H, s), 8.27-8.31 (1H, m), 7.98-8.02 (1H, m), 7.95-7.97 (1H, m), 7.53-7.58 (1H, m), 7.17-7.21 (1H, m), 6.99-7.05 (1H, m), 3.97-4.05 (2H, m), 3.53-3.59 (4H, m), 2.80-2.90 (2H, m), 2.43-2.51 (4H, m), 2.31-2.40 (1H, m), 1.83-1.92 (2H, m), 1.74 (6H, s), 1.39-1.52 (2H, m) 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.73 min (analysis condition U) 
     Example 104 
     Compound B2-13 
     8-(4,4-Difluoro-1,4′-bipiperidin-1′-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-7-2 and 4,4-difluoropiperidine hydrochloric acid salt. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.59 (1H, s), 8.25-8.32 (1H, m), 7.97-8.02 (1H, m), 7.96 (1H, s), 7.52-7.59 (1H, m), 7.16-7.21 (1H, m), 6.99-7.05 (1H, mz), 4.00-4.09 (2H, m), 3.55-3.62 (2H, m), 2.79-2.90 (2H, m), 2.55-2.67 (4H, m), 1.78-1.98 (5H, m), 1.74 (6H, s), 1.44-1.58 (2H, m) 
     LCMS: m/z 489 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 105 
     Compound B2-14 
     8-[4-((2R,6S)-2,6-Dimethyl-morpholin-4-yl)-piperidin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-7-2 and (2R,6S)-2,6-dimethylmorpholine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.60 (1H, s), 8.25-8.31 (1H, m), 7.97-8.02 (1H, m), 7.95 (1H, s), 7.51-7.58 (1H, m), 7.18 (1H, s), 6.99-7.05 (1H, m), 3.96-4. 06 (2H, m), 3.45-3.55 (2H, m), 2.80-2.91 (2H, m), 2.72-2.79 (2H, m), 2.29-2.41 (1H, m), 1.70-1.90 (10H, m), 1.40-1.53 (2H, m), 1.03 (6H, d, 6.3 Hz) 
     LCMS: m/z 483 [M+H] +   
     HPLC retention time: 1.83 min (analysis condition U) 
     Example 106 
     Compound B2-15 
     8-((3R,5S)-3,5-Dimethylpiperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 2,6-dimethylpiperazine. 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 1.76 min (analysis condition U) 
     Example 107 
     Compound B2-16-1 
     (S)-4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound B1 and (S)-3-methylpiperazine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 485 [M+H] +   
     HPLC retention time: 3.97 min (analysis condition W) 
     Example 108 
     Compound B2-16-2 
     6,6-Dimethyl-8-((S)-2-methyl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound 2-16-1. 
     LCMS: m/z 385 [M+H] +   
     HPLC retention time: 2.43 min (analysis condition W) 
     Example 109 
     Compound B2-16-3 
     8-((S)-4-Cyclobutyl-2-methyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-16-2 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.31 (1H, d, 8 Hz), 8.03 (1H, d, 12 Hz), 7.98 (1H, s), 7.59 (1H, d, 12 Hz), 7.13 (1H, s), 6.98 (1H, d, 8 Hz), 4.35-4.28 (1H, m), 3.70 (1H, d, 12 Hz), 3.02 (1H, ddd, 12, 12, 4 Hz), 2.87 (1H, d, 8 Hz), 2.74-2.67 (2H, m), 2.08-1.99 (2H, m), 1.92-1.64 (10H, m), 1.70-1.62 (2H, m), 1.12 (3H, d, 8 Hz) 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 2.59 min (analysis condition W) 
     Example 110 
     Compound B2-17 
     8-(2-Diethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 25 mg, 0.057 mmol) was dissolved in dimethoxyethane (0.5 mL), added with 2-diethylaminoethanethiol hydrochloric acid salt (19.6 mg, 2 eq.), Pd 2 (dba) 3  (2.6 mg, 0.05 eq.), Xantphos (3.3 mg, 0.1 eq.) and DIPEA (0.06 mg, 6 eq.), and the mixture was stirred at 160° C. for 30 min. The reaction solution was added to water, extracted with ethyl acetate, and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (white amorphous, 22.4 mg, 93%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 9.60 (1H, s), 8.53-8.48 (1H, m), 8.32 (1H, d, J=8.4 Hz), 7.77 (1H, s), 7.53-7.50 (2H, m), 7.38-7.35 (1H, m), 3.18-3.12 (2H, m), 2.81-2.75 (2H, m), 2.65-2.57 (4H, m), 1.76 (6H, s), 1.08-1.04 (6H, m) 
     LCMS: m/z 418 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition U) 
     Example 111 
     Compound B2-18 
     8-(2-Diisopropylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 2-diisopropylaminoethanethiol hydrochloric acid salt. 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition U) 
     Example 112 
     Compound B2-19 
     8-(2-Dimethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 2-dimethylaminoethanethiol hydrochloric acid salt. 
     LCMS: m/z 390 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition U) 
     Example 113 
     Compound B2-20 
     3-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl sulfanyl)-propionic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 3-mercaptopropionic acid. 
     LCMS: m/z 391 [M+H] +   
     HPLC retention time: 2.45 min (analysis condition U) 
     Example 114 
     Compound B2-21 
     8-(2,3-Dihydroxy-propylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 3-mercaptopropane-1,2-diol. 
     LCMS: m/z 393 [M+H] +   
     HPLC retention time: 2.15 min (analysis condition U) 
     Example 115 
     Compound B2-22-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     To trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 7.80 g, 18.0 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (6.11 g, 19.8 mmol, 1.1 eq.), Pd(PPh 3 ) 2 Cl 2  (630 mg, 0.898 mmol, 0.05 eq.), and sodium carbonate (5.71 g, 53.9 mmol, 3.0 eq.), DME (125 ml) and water (25 ml) were added. The mixture was subjected to reduced pressure under ultrasonication treatment, followed by flushing with nitrogen gas. This procedure was repeated five times and then degassed. After further stirring at 80° C. for 2 hr under nitrogen atmosphere, the mixture was cooled to room temperature, added with water (250 ml), and further stirred for 30 min. The precipitates were filtered and washed with water (50 ml). They were further washed with CH 3 CN (50 ml) to obtain the target compound as a crude product (gray powder, 7.54 g, 90%). 
     LCMS: m/z 468 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition S) 
     Example 116 
     Compound B2-22-2 
     6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-22-1. 
     LCMS: m/z 368 [M+H] +   
     HPLC retention time: 1.47 min (analysis condition S) 
     Example 117 
     Compound B2-23 
     6,6-Dimethyl-8-(1-methyl-1H-pyrazol-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound B1 and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 
     LCMS: m/z 367 [M+H] +   
     HPLC retention time: 2.42 min (analysis condition U) 
     Example 118 
     Compound B2-24 
     6,6-Dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 1.00 g, 2.302 mmol) was added with n-propanol (20 mL), potassium vinyltrifluoroborate (854 mg, 3.0 eq.), dichloro-((bis-diphenylphosphino)ferrocenyl)palladium (217 mg, 0.1 eq.) and triethylamine (1.11 ml, 3.0 eq.) in order and the resultant was stirred at 60° C. for 4 hr. Upon the completion of the reaction, water was added to the reaction solution. The resulting precipitates were filtered and washed with distilled water, and the residues were dried to obtain the title compound (666 mg, 80%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 8.90 (1H, s), 8.55 (1H, d, J=7.9 Hz), 8.40 (1H, d, J=8.5 Hz), 7.79 (1H, s), 7.58-7.61 (3H, m), 6.85 (1H, dd, J=17.7, 11.0 Hz), 5.95 (1H, d, J=17.1 Hz), 5.46 (1H, d, J=11.0 Hz), 1.84 (6H, s) 
     LCMS: m/z 313 [M+H] +   
     HPLC retention time: 3.75 min (analysis condition W) 
     Example 119 
     Compound B2-25-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     4-Methylene-piperidine-1-carboxylic acid tert-butyl ester (409 mg, 2.07 mmol, 1.2 eq.) was dissolved in THF (2 ml), added under nitrogen atmosphere with 9-BBN (0.5 M THF solution, 4.83 ml, 2.42 mmol, 1.4 eq.) and then stirred at 60° C. for 1 hr. Thereafter, 9-BBN (0.5 M THF solution, 5.52 ml, 2.77 mmol, 1.6 eq.) was further added and the mixture was stirred at 60° C. for 1 hr. The resulting mixture was cooled to room temperature, added with cesium fluoride (1.31 g, 8.60 mmol, 5.0 eq.), and stirred at room temperature for 30 min. 
     To the solution obtained from the above, DMF (18 ml) suspension comprising trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 750 mg, 1.73 mmol) and dichloro-((bisdiphenylphosphino)ferrocenyl)palladium (70.5 mg, 0.0863 mmol, 0.05 eq.) was added, and the mixture was stirred at 100° C. for 3 hr. After cooling to the room temperature, water (50 ml) was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-carboxylic acid tert-butyl ester (yellow powder, 763 mg, 91%). 
     LCMS: m/z 484 [M+H] +   
     HPLC retention time: 2.97 min (analysis condition S) 
     Example 120 
     Compound B2-25-2 
     6,6-Dimethyl-11-oxo-8-piperidin-4-yl methyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-25-1. 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 1.40 min (analysis condition S) 
     Example 121 
     Compound B2-26-1 
     Tert-butyl 4-((3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)methyl)piperidin-1-yl sulfonylcarbamic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-25-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8). 
     LCMS: m/z 563 [M+H] +   
     HPLC retention time: 2.63 min (analysis condition S) 
     Example 122 
     Compound B2-26-2 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-sulfonic acid amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-26-1. 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition S) 
     Example 123 
     Compound B2-27 
     8-(1-Isopropyl-piperidin-4-yl methyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-25-2 and acetone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.80 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.12 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.65 (1H, s), 7.61 (1H, d, 9.1 Hz), 7.30 (1H, d, 7.9 Hz), 2.75 (2H, d, 11.0 Hz), 2.65 (3H, q, 6.5 Hz), 2.04 (2H, t, 11.0 Hz), 1.77 (6H, s), 1.60-1.57 (3H, m), 1.22 (2H, t, 11.6 Hz), 0.94 (6H, d, 6.7 Hz) 
     LCMS: m/z 426 [M+H] +   
     Example 124 
     Compound B2-28 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the dimethyl formamide (3 ml) solution comprising trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 150 mg, 0.345 mmol), lithium formate monohydrate (90 mg, 5.0 eq.), 4,5-bis (diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (20 mg, 0.1 eq.), Pd 2 (dba) 3  (32 mg, 0.1 eq.), lithium chloride (88 mg, 6.0 eq.), N,N-diisopropylethylamine (241 μl, 4.0 eq.), and acetic anhydride (131 μl, 4.0 eq.) were added, and the mixture was stirred at 80° C. for 15 hr. Upon the completion of the reaction, ethyl acetate was added to the reaction solution. The organic layer was washed in order with 1 M hydrochloric acid, distilled water, and brine. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (88 mg, 76%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 13.17 (1H, s), 8.35 (1H, d, J=7.9 Hz), 8.34 (1H, s), 8.23 (1H, d, J=7.9 Hz), 8.07 (1H, s), 8.02 (1H, d, J=9.1 Hz), 7.64 (1H, d, J=7.9 Hz), 1.80 (6H, s) 
     LCMS: m/z 331 [M+H] +   
     HPLC retention time: 3.08 min (analysis condition W) 
     Example 125 
     Compound B2-29 
     8-Formyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the THF (24 ml) and distilled water (6 ml) suspension of 6,6-dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-24, 600 mg, 1.920 mmol), t-butanol solution of osmium tetraoxide (192 μl, 0.1 eq.) and sodium meta periodate (821 mg, 2.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. Aqueous solution of sodium thiosulfate (0.3 M) was added to the solution, which was then extracted with an ethyl acetate. The organic layer was washed with 10% aqueous solution of disodium ethylenediamine tetraacetic acid. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (470 mg, 77%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.95 (1H, s), 10.20 (1H, s), 8.48 (1H, s), 8.42 (1H, d, J=8.5 Hz), 8.36 (1H, d, J=8.5 Hz), 8.07 (1H, s), 8.02 (1H, d, J=7.9 Hz), 7.67 (1H, d, J=7.9 Hz), 1.85 (6H, s) 
     LCMS: m/z 315 [M+H] +   
     HPLC retention time: 3.38 min (analysis condition W) 
     Example 126 
     Compound B3-1 
     5,6,6-Trimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound B2-3. 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 2.62 min (analysis condition U) 
     Example 127 
     Compound B3-2-1 
     Tert-butyl 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)piperazin-1-yl sulfonylcarbamic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-5-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8). 
     LCMS: m/z 550 [M+H] +   
     HPLC retention time: 2.39 min (analysis condition S) 
     Example 128 
     Compound B3-2-2 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic acid amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-2-1. 
     LCMS: m/z 450 [M+H] +   
     HPLC retention time: 1.82 min (analysis condition S) 
     Example 129 
     Compound B3-3 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-5-2 and dimethylsulfamoyl chloride. 
     LCMS: m/z 478 [M+H] +   
     HPLC retention time: 2.45 min (analysis condition S) 
     Example 130 
     Compound B3-4 
     4-(3-Cyano-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     To the DMF suspension of 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic acid amide (Compound B3-2-2, 20 mg, 0.04 mmol) and sodium hydride (21.4 mg, 12 eq.), iodomethane (28 μl, 10 eq.) was added and stirred at room temperature overnight. Water was added to the reaction solution, followed by filtration to obtain the target compound (25.8 mg, 100%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.43 (1H, d, J=8.2 Hz), 8.31 (1H, s), 8.03 (1H, d, J=8.9 Hz), 7.64 (1H, dd, J=8.1, 1.3 Hz), 7.30 (1H, d, J=2.0 Hz), 7.08 (1H, dd, J=8.9, 2.0 Hz), 4.16 (3H, s), 3.43-3.53 (4H, t, J=4.7 Hz), 3.26-3.41 (4H, s), 2.82 (6H, s), 1.87 (6H, s). 
     LCMS: m/z 492 [M+H] +   
     HPLC retention time: 2.69 min (analysis condition S) 
     Example 131 
     Compound B3-5 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound F5-36. 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 132 
     Compound B3-6 
     8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-5-2 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=8.2 Hz), 8.01 (1H, d, J=8.8 Hz), 7.96 (1H, s), 7.55 (1H, d, J=8.2 Hz), 7.19 (1H, d, J=2.2 Hz), 7.03 (1H, dd, J=2.4, 8.8 Hz), 2.71-2.75 (1H, m), 2.37-2.39 (4H, m), 1.98-2.00 (2H, m), 1.77-1.85 (2H, m), 1.74 (6H, s), 1.63-1.68 (2H, m). 
     LCMS: m/z 425 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition U) 
     Example 133 
     Compound B3-7 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-5-2 and 3-oxetanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.29 (1H, dd, J=8.2, 0.59 Hz), 8.02 (1H, d, J=9.0 Hz), 7.97 (1H, d, J=0.59 Hz), 7.56 (1H, dd, J=8.0, 1.4 Hz), 7.22 (1H, d, J=2.3 Hz), 7.04 (1H, dd, J=8.8, 2.2 Hz), 4.56-4.59 (2H, m), 4.47-4.50 (2H, m), 3.43-3.48 (1H, m), 3.39-3.42 (4H, m), 2.40-2.42 (4H, m), 1.74 (6H, s) 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 1.67 min (analysis condition U) 
     Example 134 
     Compound B3-8 
     8-(2-Diethylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-(2-Diethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-17, 16.8 mg, 0.0402 mmol) was dissolved in methanol (1.5 mL), added with oxone (54.3 mg, 2.2 eq.) which had been dissolved in water (0.5 mL), and then stirred at room temperature for 2 hr. The reaction solution was concentrated, extracted with ethyl acetate, washed with saturated sodium hydrogen carbonate, and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (white solid, 5.8 mg, 32%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 9.29 (1H, s), 8.61 (1H, d, J=8.2 Hz), 8.52 (1H, d, J=8.0 Hz), 8.21 (1H, s), 8.01 (1H, d, J=8.2 Hz), 7.81 (1H, s), 7.61 (1H, d, J=8.2 Hz), 3.33 (2H, t, J=7.4 Hz), 2.95 (2H, t, J=7.4 Hz), 2.41 (4H, q, J=7.2 Hz), 1.86 (6H, s), 0.89 (4H, t, J=7.1 Hz) 
     LCMS: m/z 450 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition U) 
     Example 135 
     Compound B3-9 
     8-(2-Diisopropylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-18. 
     LCMS: m/z 478 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition U) 
     Example 136 
     Compound B3-10 
     8-(2-Dimethylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-19. 
     LCMS: m/z 422 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition U) 
     Example 137 
     Compound B3-11 
     3-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-sulfonyl)-propionic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-20. 
     LCMS: m/z 423 [M+H] +   
     HPLC retention time: 2.28 min (analysis condition U) 
     Example 138 
     Compound B3-12 
     8-(2,3-Dihydroxy-propane-1-sulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-21. 
     LCMS: m/z 425 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition U) 
     Example 139 
     Compound B3-13-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Compound B2-22-1, 16.2 g, 34.6 mmol) was dissolved in THF (800 ml) and methanol (230 ml), added with 10 wt % Pd/C (3.2 g), and stirred under hydrogen atmosphere for 19 hr. The solid was filtered through Celite, eluted with a mixture solvent (400 ml; THF/methanol=4/1), and concentrated under reduced pressure. The residues were dissolved in ethyl acetate (400 ml), and then washed with 1% aqueous solution of N-acetylcysteine, saturated aqueous solution of NaHCO 3  and saturated brine. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the title compound as a crude product (white powder, 14.0 g, 86%). 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 2.88 min (analysis condition S) 
     Example 140 
     Compound B3-13-2 
     6,6-Dimethyl-11-oxo-8-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-13-1. 
     LCMS: m/z 370 [M+H] +   
     HPLC retention time: 1.30 min (analysis condition S) 
     Example 141 
     Compound B3-14 
     8-(1,2-Dihydroxy-ethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the THF (1 ml) solution of 6,6-dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-24, 20 mg, 0.064 mmol), t-butanol solution of osmium tetraoxide (19 μl, 0.3 eq.) and 50% aqueous solution of N-methylmorpholine-N-oxide (30 μl, 2.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. To the reaction solution, 10% aqueous solution of disodium ethylenediamine tetraacetic acid was added, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (21 mg, 63%). 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.41 (1H, d, J=7.9 Hz), 8.29 (1H, d, J=7.9 Hz), 7.87 (1H, s), 7.86 (1H, s), 7.57 (1H, d, J=7.9 Hz), 7.52 (1H, d, J=6.7 Hz), 4.85 (1H, dd, J=7.0, 4.6 Hz), 3.73 (1H, dd, J=11.3, 4.6 Hz), 3.68 (1H, dd, J=11.3, 7.0 Hz), 1.83 (6H, s) 
     LCMS: m/z 347 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition W) 
     Example 142 
     Compound B3-15 
     6,6-Dimethyl-8-(morpholine-4-carbonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the tetrahydrofuran (1 ml) solution of 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (Compound B2-28, 15 mg, 0.045 mmol), morpholine (6 μl, 1.5 eq.), hexafluorophosphoric acid uronium 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethylmethane aminium (HATU) (26 mg, 1.5 eq.), and N,N-diisopropylethylamine (24 μl, 3.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. The reaction solution was filtered to remove insoluble matters and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (11 mg, 55%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.85 (1H, s), 8.33 (1H, d, J=8.5 Hz), 8.27 (1H, d, J=7.9 Hz), 8.03 (1H, s), 7.92 (1H, s), 7.63 (1H, d, J=8.5 Hz), 7.54 (1H, d, J=7.9 Hz), 3.52-3.77 (6H, m), 3.30-3.42 (2H, m), 1.79 (6H, s) 
     LCMS: m/z 400 [M+H] +   
     HPLC retention time: 2.96 min (analysis condition W) 
     Example 143 
     Compound B3-16 
     8-(4-Methanesulfonyl-piperazin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-methanesulfonylpiperazine. 
     LCMS: m/z 477 [M+H] +   
     HPLC retention time: 3.03 min (analysis condition W) 
     Example 144 
     Compound B3-17 
     8-(4-Hydroxy-piperidin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and piperidin-4-ol. 
     LCMS: m/z 414 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition W) 
     Example 145 
     Compound B3-18 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-aminopropane-1,3-diol. 
     LCMS: m/z 404 [M+H] +   
     HPLC retention time: 2.60 min (analysis condition W) 
     Example 146 
     Compound B3-19 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-methanesulfonyl-ethyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-methanesulfonylethylamine. 
     LCMS: m/z 436 [M+H] +   
     HPLC retention time: 2.87 min (analysis condition W) 
     Example 147 
     Compound B3-20 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (1,1-dioxo-tetrahydro-thiophen-3-yl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (1,1-dioxotetrahydrothiophen-3-yl)amine 
     LCMS: m/z 448 [M+H] +   
     HPLC retention time: 1.70 min (analysis condition S) 
     Example 148 
     Compound B3-21 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid ((R)-2,3-dihydroxy-propyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (R)-(+)-3-amino-1,2-propanediol. 
     LCMS: m/z 404 [M+H] +   
     HPLC retention time: 1.38 min (analysis condition S) 
     Example 149 
     Compound B3-22 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid bis-(2-hydroxy-ethyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and N,N-diethanolamine. 
     LCMS: m/z 418 [M+H] +   
     HPLC retention time: 1.35 min (analysis condition S) 
     Example 150 
     Compound B3-23 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid oxetan-3-yl amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and oxetan-3-yl amine. 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 1.63 min (analysis condition S) 
     Example 151 
     Compound B3-24 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-ethoxy)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-aminooxy-ethanol. 
     LCMS: m/z 390 [M+H] +   
     HPLC retention time: 1.54 min (analysis condition S) 
     Example 152 
     Compound B3-25-1 
     2-[(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carbonyl)-amino]-ethyl}-carbamic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (2-amino-ethyl)-carbamic acid tert-butyl ester. 
     LCMS: m/z 473 [M+H] +   
     HPLC retention time: 2.08 min (analysis condition S) 
     Example 153 
     Compound B3-25-2 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-amino-ethyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-25-1. 
     LCMS: m/z 373 [M+H] +   
     HPLC retention time: 1.19 min (analysis condition S) 
     Example 154 
     Compound B3-25-3 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-methanesulfonylamino-ethyl)-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-25-2. 
     LCMS: m/z 451 [M+H] +   
     HPLC retention time: 1.62 min (analysis condition S) 
     Example 155 
     Compound B3-26 
     3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-ethyl)-methyl-amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-methylamino-ethanol. 
     LCMS: m/z 388 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition S) 
     Example 156 
     Compound B3-27-1 
     Tert-butyl N-(2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8carboxamide)ethyl)sulfamoylcarbamic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-25-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8). 
     LCMS: m/z 552 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition S) 
     Example 157 
     Compound B3-27-2 
     3-Cyano-6,6-dimethyl-11-oxo-N-(2-(sulfamoylamino)ethyl)-6,11-dihydro-5H-benzo[b]carbazol-8-carboxamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-27-1. 
     LCMS: m/z 452 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition S) 
     Example 158 
     Compound B3-28 
     8-[4-(2-Hydroxy-ethyl)-piperazin-1-carbonyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-piperazin-1-yl ethanol. 
     LCMS: m/z 443 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition U) 
     Example 159 
     Compound B3-29 
     8-(4-Tert-butyl-piperazin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-tert-butylpiperazine. 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 160 
     Compound B3-30 
     8-[4-(2-Methoxy-ethyl)-piperazin-1-carbonyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-(2-methoxyethyl)piperazine. 
     LCMS: m/z 457 [M+H] +   
     HPLC retention time: 1.83 min (analysis condition U) 
     Example 161 
     Compound B3-31-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carbonyl)-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and piperazine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 499 [M+H] +   
     HPLC retention time: 2.63 min (analysis condition U) 
     Example 162 
     Compound B3-31-2 
     6,6-Dimethyl-11-oxo-8-(piperazin-1-carbonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-31-1. 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 1.78 min (analysis condition U) 
     Example 163 
     Compound B3-32 
     6,6-Dimethyl-8-morpholin-4-yl methyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the THF (1 ml) solution of Compound B2-29 (30 mg, 0.095 mmol), morpholine (6 μl, 1.5 eq.) and sodium triacetoxyborohydride (81 mg, 2.0 eq.) were added and stirred at room temperature for 1 hr. The reaction solution was filtered to remove insoluble matters, and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (19 mg, 50%). 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.41 (1H, d, 7.9 Hz), 8.27 (1H, d, 8.5 Hz), 7.87 (1 s), 7.81 (1H, s), 7.56 (1H, d, 8.5 Hz), 7.49 (1H, d, 7.9 Hz), 3.71 (4H, t, 4.6 Hz), 3.68 (2H, s), 2.51 (4H, t, 4.6 Hz), 1.82 (6H, s) 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 2.41 min (analysis condition W) 
     Example 164 
     Compound B3-33 
     6,6-Dimethyl-8-(4-methyl-piperazin-1-yl methyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 1-methylpiperazine. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.41 (1H, d, 7.9 Hz), 8.26 (1H, d, 7.9 Hz), 7.88 (1 s), 7.81 (1H, s), 7.56 (1H, d, 7.9 Hz), 7.48 (1H, d, 7.9 Hz), 3.70 (2H, s), 2.42-2.78 (8H, m), 2.31 (3H, s), 1.82 (6H, s) 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition W) 
     Example 165 
     Compound B3-34 
     8-[4-(1,1-Dioxide-4-thiomorpholinyl)methyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and thiomorpholine 1,1-dioxide. 
     LCMS: m/z 434 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition W) 
     Example 166 
     Compound B3-35 
     8-(4-Methanesulfonyl-piperazin-1-yl methyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 1-methanesulfonylpiperazine. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.41 (1H, d, 8.5 Hz), 8.28 (1H, d, 7.9 Hz), 7.87 (1 s), 7.80 (1H, s), 7.56 (1H, d, 8.5 Hz), 7.50 (1H, d, 7.9 Hz), 3.73 (2H, s), 3.24-3.28 (4H, m), 2.85 (3H, s), 2.59-2.65 (4H, m), 1.82 (6H, s) 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition W) 
     Example 167 
     Compound B3-36 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperazine-1-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and piperazine-1-sulfonic acid dimethylamide. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.79 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.18 (1H, d, 7.9 Hz), 8.00 (1 s), 7.77 (1H, s), 7.60 (1H, d, 7.9 Hz), 7.46 (1H, d, 7.9 Hz), 3.67 (2H, s), 3.18-3.23 (4H, m), 2.76 (6H, s), 2.45-2.50 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 492 [M+H] +   
     HPLC retention time: 2.58 min (analysis condition W) 
     Example 168 
     Compound B3-37 
     6,6-Dimethyl-11-oxo-8-[(2,2,2-trifluoro-ethylamino)-methyl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 2,2,2-trifluoroethylamine. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 2.73 min (analysis condition W) 
     Example 169 
     Compound B3-38 
     8-Hydroxymethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The by-product obtained from the synthesis of Compound B3-37 was purified by high performance liquid chromatography to obtain the target compound. 
     LCMS: m/z 317 [M+H] +   
     HPLC retention time: 2.91 min (analysis condition W) 
     Example 170 
     Compound B4-1 
     8-(1-Cyclobutyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.73 (1H, s), 8.28-8.33 (1H, m), 8.09-8.14 (1H, m), 7.99 (1H, s), 7.72 (1H, s), 7.56-7.62 (1H, m), 7.34-7.41 (1H, m), 3.52-3.64 (2H, m), 2.85-2.95 (2H, m), 2.56-2.75 (2H, m), 1.91-2.04 (2H, m), 1.56-1.84 (14H, m) 
     LCMS: m/z 424 [M+H] +   
     HPLC retention time: 1.87 min (analysis condition U) 
     Example 171 
     Compound B4-2 
     8-(1-Methanesulfonyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and mesyl chloride. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.77 (1H, s), 8.31 (1H, d, 8.6 Hz), 8.15 (1H, d, 8.2 Hz), 8.00 (1H, s), 7.77 (1H, s), 7.59 (1H, d, 7.3 Hz), 7.42 (1H, d, 8.6 Hz), 3.74-3.70 (1H, m), 2.93 (3H, s), 2.86-2.77 (4H, m), 1.93-1.87 (4H, m), 1.77 (6.0H, s) 
     LCMS: m/z 448 [M+H] +   
     HPLC retention time: 2.37 min (analysis condition S) 
     Example 172 
     Compound B4-3-1 
     Tert-butyl4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)piperidin-1-yl sulfonylcarbamic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridine-1-yl-sulfonyl]azanide. 
     LCMS: m/z 549 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition S) 
     Example 173 
     Compound B4-3-2 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic acid amide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-3-1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 8.29 (1H, d, 7.9 Hz), 8.14 (1H, d, 8.5 Hz), 7.97 (1H, s), 7.76 (1H, s), 7.55 (1H, d, 8.5 Hz), 7.41 (1H, d, 7.9 Hz), 6.79 (2H, s), 3.63 (2H, d, 12.2 Hz), 2.80-2.73 (1H, m), 2.70-2.64 (2H, m), 1.96-1.93 (2H, m), 1.87-1.81 (2H, m), 1.77 (6H, s) 
     LCMS: m/z 449 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition S) 
     Example 174 
     Compound B4-4 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic acid methylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and 2-oxooxazolidine-3-sulfonic acid methylamide. 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition S) 
     Example 175 
     Compound B4-5 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and dimethylsulfamoyl chloride. 
     LCMS: m/z 477 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition S) 
     Example 176 
     Compound B4-6 
     6,6-Dimethyl-8-(1-methyl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and iodomethane. 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 1.50 min (analysis condition S) 
     Example 177 
     Compound B4-7 
     8-(1-Isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and acetone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.77 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.13 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.73 (1H, s), 7.61 (1H, d, 9.1 Hz), 7.39 (1H, d, 9.8 Hz), 2.93 (2H, d, 11.0 Hz), 2.77-2.71 (1H, m), 2.67-2.62 (1H, m), 2.25 (2H, t, 10.1 Hz), 1.80-1.73 (10H, m), 1.02 (6H, d, 6.7 Hz) 
     LCMS: m/z 412 [M+H] +   
     HPLC retention time: 1.60 min (analysis condition S) 
     Example 178 
     Compound B4-8 
     6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and oxetan-3-one. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.74 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.13 (1H, d, 7.9 Hz), 8.00 (1H, s), 7.74 (1H, s), 7.61 (1H, d, 9.8 Hz), 7.40 (1H, d, 7.9 Hz), 4.56 (2H, t, 6.7 Hz), 4.46 (2H, t, 6.1 Hz), 3.46-3.39 (1H, m), 2.85-2.82 (2H, m), 2.71-2.64 (1H, m), 1.92-1.86 (2H, m), 1.82-1.79 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition S) 
     Sulfuric Acid Salt of Compound B4-8 
     6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved at 80° C. in a mixture of 5 volumes of DMA and 1.4 volumes of 2 N sulfuric acid. After cooling to room temperature, 15 volumes of acetone were added dropwise, and the precipitated solids were filtered and dried to obtain sulfuric acid salt of 6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.81 (1H, s), 10.26 (1H, br. s), 8.33 (1H, d, 8.3 Hz), 8.21 (1H, d, 8.3 Hz), 8.04 (1H, s), 7.75 (1H, s), 7.63 (1H, d, 8.3 Hz), 7.41 (1H, d, 8.3 Hz), 4.85-4.70 (4H, m), 4.50-4.40 (1H, br. s), 3.60-3.00 (6H, br. m), 2.20-2.10 (2H, m), 2.05-1.90 (2H, m), 1.79 (6H, s) 
     LCMS: m/z 426 [M+H] +   
     Example 179 
     Compound B4-9 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-carboxylic acid ethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B-3-13-2 and ethylisocyanate. 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 2.20 min (analysis condition S) 
     Example 180 
     Compound B4-10 
     8-[1-(Imidazole-1-sulfonyl)-piperidin-4-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method disclosed in Journal of Organic Chemistry, 2003, page 115, 6,6-dimethyl-11-oxo-8-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B3-13-2, 10 mg, 0.027 mmol) was reacted with 3-(imidazole-1-sulfonyl)-1-methyl-3H-imidazol-1-ium (19 mg, 2 eq.). After removing the solvent, the residues were purified by liquid chromatography to obtain the title compound (3 mg). 
     LCMS: m/z 500 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition C) 
     Example 181 
     Compound CC1 
     3-Methoxy-5,5-dimethyl-6-oxo-5,6,7,8-tetrahydro-naphthalen-2-sulfonyl chloride 
     
       
         
         
             
             
         
       
     
     To the dichloromethane (2 ml) solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 200 mg, 0.980 mmol), chlorosulfonic acid (110 μl, 1.70 eq.) was added and the mixture was stirred at room temperature for 2 hr. To the reaction solution, oxalyl chloride (297 μl, 3.0 eq.) and N,N-dimethyl formamide (45 μl, 0.6 eq.) were added in three divided portions, and the mixture was stirred at room temperature for 30 min. The reaction solution was concentrated under reduced pressure to obtain the title compound (295 mg). Since the title compound is unstable, its structure was identified in the next step. 
     Example 182 
     Compound CC2-1 
     7-Methoxy-1,1-dimethyl-6-(pyrrolidine-1-sulfonyl)-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     The THF (4 ml) solution of 3-methoxy-5,5-dimethyl-6-oxo-5,6,7,8-tetrahydro-naphthalen-2-sulfonyl chloride (Compound CC1, 295 mg, 0.974 mmol) was cooled to 0° C., and the tetrafuran (1 ml) solution combining pyrrolidine (121 μl, 1.5 eq.) and triethylamine (272 μl, 2 eq.) was added dropwise thereto over 2 min. The mixture was stirred at 0° C. until Compound CC-1 disappears. The reaction solution was added with distilled water and extracted with ethyl acetate. The organic layer was washed with 10% aqueous solution of disodium ethylenediamine tetraacetic acid. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (246 mg, 75%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 7.76 (1H, s), 6.93 (1H, s), 3.95 (3H, s), 3.37-3.46 (4H, m), 3.09 (0.0H, t, J=6.9 Hz), 2.69 (0.0H, t, J=6.9 Hz), 1.82-1.91 (4H, m), 1.47 (6H, s) 
     LCMS: m/z 338 [M+H] +   
     HPLC retention time: 3.21 min (analysis condition W) 
     Example 183 
     Compound CC2-2 
     7-Methoxy-1,1-dimethyl-6-(4-methyl-piperazine-1-sulfonyl)-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound CC2-1, the title compound was prepared from Compound CC1 and N-methylpiperazine. 
     LCMS: m/z 367 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition Y) 
     Example 184 
     Compound CC3-1 
     8-Methoxy-6,6-dimethyl-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared from Compound CC2-1. 
     LCMS: m/z 436 [M+H] +   
     HPLC retention time: 3.76 min (analysis condition W) 
     Example 185 
     Compound CC3-2 
     3-Bromo-8-methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound CC2-2. 
     LCMS: m/z 519 [M+H] +   
     HPLC retention time: 2.99 min (analysis condition Y) 
     Example 186 
     Compound CC4-1 
     8-Methoxy-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound CC3-1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.86 (1H, s), 8.60 (1H, s), 8.30 (1H, d, J=8.5 Hz), 8.01 (1H, s), 7.60 (1H, s), 7.59 (1H, d, J=8.5 Hz), 4.09 (3H, s), 3.21-3.42 (4H, m), 1.72-1.90 (10H, m) 
     LCMS: m/z 450 [M+H] +   
     HPLC retention time: 3.40 min (analysis condition W) 
     Example 187 
     Compound CC4-2 
     3-Bromo-8-methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound CC3-2. 
     LCMS: m/z 532, 534 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition U) 
     Example 188 
     Compound CC-4-3 
     8-Methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound CC4-2. 
     LCMS: m/z 479 [M+H] +   
     HPLC retention time: 1.93 min (analysis condition U) 
     Example 189 
     Compound C1-1 
     Dimethyl-sulfamic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 50 mg, 0.165 mmol) was dissolved in DMF (1.5 mL), added with sodium hydride (13 mg, 2.0 eq.) and dimethylsulfamoyl chloride (0.02 mL, 1.2 eq.), and then stirred at room temperature for 1 hr. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the target compound (yellowish white powder, 62 mg, 92%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.87 (1H, s), 8.40-8.30 (2H, m), 8.05 (1H, s), 7.82 (1H, d, J=1.8 Hz), 7.64 (1H, d, J=7.9 Hz), 7.50 (1H, dd, J=8.5, 2.4 Hz), 2.96 (6H, s), 1.81 (6H, s) 
     LCMS: m/z 410 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition S) 
     Example 190 
     Compound C1-2 
     Morpholine-4-sulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-17, the title compound was prepared as a crude product from Compound A6 and Compound A8-18-0. 
     Example 191 
     Compound C1-4 
     4-Methyl-piperazine-1-sulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-17, the title compound was prepared as a crude product from Compound A6 and Compound A8-19-0. 
     Example 192 
     Compound C2-1 
     3-Cyano-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     To dimethyl-sulfamic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound C1-1, 250 mg, 0.610 mmol), aluminum chloride (1.0 M, nitromethane solution (1.8 mL, 3.0 eq.)) was added and the mixture was stirred at 160° C. for 10 min under irradiation with microwave. Water was added to the reaction solution, which was then extracted with dichloromethane. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (yellowish white powder, 99 mg, 40%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 11.72 (1H, s), 8.50 (1H, s), 8.32 (1H, d, J=8.5 Hz), 8.02 (1H, s), 7.62 (1H, d, J=7.9 Hz), 7.25 (1H, s), 2.80 (6H, s), 1.75 (6H, s). 
     LCMS: m/z 410 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition S) 
     Example 193 
     Compound C2-2 
     8-Hydroxy-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound CC4-1. 
     LCMS: m/z 436 [M+H] +   
     HPLC retention time: 3.32 min (analysis condition W) 
     Example 194 
     Compound C2-3 
     8-Hydroxy-6,6-dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound C2-1, the title compound was prepared from Compound C1-2. 
     LCMS: m/z 452 [M+H] +   
     HPLC retention time: 1.89 min (analysis condition S) 
     Example 195 
     Compound C2-4 
     8-Hydroxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound CC4-3. 
     LCMS: m/z 465 [M+H] +   
     HPLC retention time: 1.87 min (analysis condition U) 
     Example 196 
     Compound C3-1 
     Trifluoro-methanesulfonic acid 3-cyano-9-dimethylsulfamoyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound C2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 13.05 (1H, s), 8.67 (1H, s), 8.32 (1H, d, J=8.2 Hz), 8.06 (2H, m), 7.67 (1H, dd, J=7.9, 1.3 Hz), 2.79 (6H, s), 1.84 (6H, s). 
     LCMS: m/z 542 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition S) 
     Example 197 
     Compound C3-2 
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound C2-2. 
     LCMS: m/z 568 [M+H] +   
     HPLC retention time: 4.00 min (analysis condition W) 
     Example 198 
     Compound C4-1 
     3-Cyano-8-(2-methoxy-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1 and 1-bromo-2-methoxy-ethane. 
       1 H-NMR (300 MHz, DMSO-d 6 ) σppm; 12.8 (s, 1H), 8.58 (s, 1H), 8.31 (d, 1H, J=8.4 Hz), 8.03 (s, 1H), 7.62 (m, 2H), 4.47 (m, 2H), 3.75 (m, 2H), 3.32 (s, 3H), 2.27 (s, 6H), 1.83 (s, 6H) 
     LCMS: m/z 468 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition U) 
     Example 199 
     Compound C4-2 
     3-Cyano-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.57 (1H, s), 8.29 (1H, d, J=8.4 Hz), 8.02 (1H, s), 7.70-7.60 (2H, m), 4.37 (2H, t, J=6.3 Hz), 2.84 (2H, m), 2.80 (6H, s), 2.64-2.53 (4H, m), 1.83 (6H, s), 0.98 (6H, t, J=7.1 Hz). 
     LCMS: m/z 509 [M+H] +   
     HPLC retention time: 1.55 min (analysis condition S) 
     Example 200 
     Compound C4-3 
     3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1 and iodomethane. 
     LCMS: m/z 424 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition S) 
     Example 201 
     Compound C4-4 
     3-Cyano-6,6-dimethyl-11-oxo-8-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1 and Compound A8-1, the title compound was prepared from Compound C2-1 and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 493 [M+H] +   
     HPLC retention time: 1.49 min (analysis condition S) 
     Example 202 
     Compound C4-5 
     3-Cyano-6,6-dimethyl-8-(2-morpholin-4-yl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 2-morpholin-4-yl-ethanol. 
     LCMS: m/z 523 [M+H] +   
     HPLC retention time: 1.64 min (analysis condition S) 
     Example 203 
     Compound C4-6 
     3-Cyano-8-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 2-(1,1-dioxothiomorpholino)ethanol. 
     LCMS: m/z 571 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition S) 
     Example 204 
     Compound C4-7 
     3-Cyano-8-(1-ethyl-piperidin-4-yl oxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 1-ethyl-piperidin-4-ol. 
     LCMS: m/z 521 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 205 
     Compound C4-8 
     3-Cyano-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.61 (1H, s), 8.30 (1H, d, J=8.1 Hz), 8. 04 (1H, s), 7.87 (1H, s), 7.62 (1H, dd, J=8.2, 1.8 Hz), 3.17-3.06 (2H, m), 2.75-2.70 (6H, s), 2.67-2.58 (2H, m), 1.81 (6H, s), 1.02 (6H, d, J=6.4 Hz). 
     LCMS: m/z 520 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 206 
     Compound C4-9 
     3-Cyano-8-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and 2-piperazin-1-yl-ethanol. 
     LCMS: m/z 522 [M+H] +   
     HPLC retention time: 1.40 min (analysis condition S) 
     Example 207 
     Compound C4-10 
     3-Cyano-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and morpholine. 
     LCMS: m/z 479 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition S) 
     Example 208 
     Compound C4-11 
     4-(3-Cyano-9-dimethylsulfamoyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and piperazine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 578 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition S) 
     Example 209 
     Compound C4-12 
     3-Cyano-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from C4-11. 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.78 (1H, s), 8.39 (1H, dd, J=8.2, 0.7 Hz), 7.88 (1H, m), 7.75 (1.1H, s), 7.55 (1H, dd, J=8.2, 1.5 Hz), 3.15 (4H, m), 3.04 (4H, m), 2.82 (s, 6H), 1.85 (6H, s) 
     LCMS: m/z 478 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 210 
     Compound C4-13 
     6,6-Dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-2 and 4-(1-pyrrolidyl)-piperidine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.83 (1H, s), 8.64 (1H, s), 8.32 (1H, d, 8.2 Hz), 8.03 (1H, s), 7.80 (1H, s), 7.63 (1H, d, 8.2 Hz), 2.87-2.94 (4H, m), 1.94-1.99 (4H, m), 1.80 (6H, s), 1.58-1.76 (10H, m) 
     LCMS: m/z 572 [M+H] +   
     HPLC retention time: 2.81 min (analysis condition W) 
     Example 211 
     Compound C4-14 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-3. 
     LCMS: m/z 551 [M+H] +   
     HPLC retention time: 1.46 min (analysis condition S) 
     Example 212 
     Compound C4-15 
     6,6-Dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-3 and tetrahydropyran-4-ol. 
     LCMS: m/z 536 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition S) 
     Example 213 
     Compound C4-16 
     6,6-Dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-4 and tetrahydropyran-4-ol. 
     LCMS: m/z 549 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition U) 
     Example 214 
     Compound C4-17 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the target compound was prepared from Compound C2-3. 
     LCMS: m/z 564 [M+H] +   
     HPLC retention time: 1.20 min (analysis condition S) 
     Example 215 
     Compound C5 
     3-Cyano-8-methoxy-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound C4-3. 
     LCMS: m/z 438 [M+H] +   
     HPLC retention time: 2.29 min (analysis condition S) 
     Example 216 
     Compound D0-1-1 
     7-Methoxy-1,1-dimethyl-6-nitro-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     Tetrabutylammonium nitrate (2.47 g, 1.07 eq.) was dissolved in dichloromethane, and added with trifluoromethanesulfonic anhydride (1.33 ml, 1.07 eq.) at 0° C. The mixture was stirred for 1 hr, added with DCM solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 1.55 g, 7.59 mmol), and then stirred at 0° C. for 2 hr and 30 min. The reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (pale yellow solid, 1.144 g, 60%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 7.79 (1H, s), 7.28 (1H, s), 3.95 (3H, s), 3.06 (2H, t, J=6.9 Hz), 2.64 (2H, t, J=6.9 Hz), 1.41 (6H, s). 
     HPLC retention time: 2.03 min (analysis condition S) 
     Example 217 
     Compound D0-1-2 
     7-Methoxy-1,1-dimethyl-8-nitro-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound D0-1-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 7.44 (1H, d, J=8.6 Hz), 7.23 (1H, d, J=8.6 Hz), 3.84 (3H, s), 3.07 (2H, t, J=6.9 Hz), 2.65 (2H, t, J=6.9 Hz), 1.35 (6H, s) 
     HPLC retention time: 2.15 min (analysis condition S) 
     Example 218 
     Compound D0-2-1 
     3-Bromo-8-methoxy-6,6-dimethyl-9-nitro-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound D0-1-1. 
     LCMS: m/z 401,403 [M+H] +   
     HPLC retention time: 3.07 min (analysis condition S) 
     Example 219 
     Compound D0-2-2 
     3-Bromo-8-methoxy-6,6-dimethyl-7-nitro-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound D0-1-2. 
     LCMS: m/z 401, 403 [M+H] +   
     HPLC retention time: 3.10 min (analysis condition S) 
     Example 220 
     Compound D0-3-1 
     3-Bromo-8-methoxy-6,6-dimethyl-9-nitro-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound D0-2-1. 
     LCMS: m/z 415, 417 [M+H] +   
     HPLC retention time: 3.07 min (analysis condition S) 
     Example 221 
     Compound D0-3-2 
     3-Bromo-8-methoxy-6,6-dimethyl-7-nitro-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound D0-2-2. 
     LCMS: m/z 415, 417 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition S) 
     Example 222 
     Compound D0-4-1 
     8-Methoxy-6,6-dimethyl-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound D0-3-1. 
     LCMS: m/z 362 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition S) 
     Example 223 
     Compound D0-4-2 
     8-Methoxy-6,6-dimethyl-7-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound D0-3-2. 
     LCMS: m/z 362 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition S) 
     Example 224 
     Compound D0-5-1 
     8-Hydroxy-6,6-dimethyl-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound D0-4-1. 
     LCMS: m/z 348 [M+H] +   
     HPLC retention time: 2.28 min (analysis condition S) 
     Example 225 
     Compound D0-5-2 
     8-Hydroxy-6,6-dimethyl-7-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound D0-4-2. 
     LCMS: m/z 348 [M+H] +   
     HPLC retention time: 2.23 min (analysis condition S) 
     Example 226 
     Compound D1 
     6,6-Dimethyl-8-(1-methyl-piperidin-4-yl oxy)-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound D0-5-1 and 1-methylpiperidin-4-ol. 
     LCMS: m/z 445 [M+H] +   
     HPLC retention time: 1.64 min (analysis condition S) 
     Example 227 
     Compound D2 
     9-Amino-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6,6-Dimethyl-8-(1-methyl-piperidin-4-yl oxy)-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound D1, 83 mg, 0.19 mmol) was dissolved in ethanol, added with aqueous solution of ammonium acetate and aqueous solution of titanium (III) chloride, and then the mixture was stirred at room temperature for 45 min. The reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the title compound (yellow solid, 60 mg, 78%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.61 (1H, br. s), 8.28-8.34 (1H, m), 7.94-8.00 (1H, m), 7.57 (1H, dd, J=8.2, 1.4 Hz), 7.46 (1H, s), 7.19 (1H, s), 4.93 (1.8H, s), 4.65 (1.0H, s), 4.06-4.15 (1H, m), 3.34 (5.7H, s), 3.16-3.18 (2H, m), 2.55-2.67 (2H, m), 2.17-2.33 (5H, m), 1.89-2.07 (2H, m), 1.65-1.81 (8H, m) 
     LCMS: m/z 415 [M+H] +   
     HPLC retention time: 1.12 min (analysis condition S) 
     Example 228 
     Compound D3-1 
     N-[3-Cyano-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound D2 and methanesulfonyl chloride. 
     LCMS: m/z 493 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 229 
     Compound D3-2 
     3-Cyano-6,6-dimethyl-11-oxo-8-(1-methylpiperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound D2 and dimethylsulfamoyl chloride. 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.34-8.42 (2.0H, m), 7.85 (1.0H, s), 7.47-7.58 (1.0H, m), 7.32 (1.0H, s), 4.73-4.89 (1H, m), 2.75-2.91 (8H, m), 2.38-2.52 (2H, m), 2.34 (3H, s), 2.06-2.21 (2H, m), 1.87-2.05 (2H, m), 1.80 (6H, s). 
     LCMS: m/z 522 [M+H] +   
     HPLC retention time: 1.66 min (analysis condition S) 
     Example 230 
     Compound D3-3 
     N-[3-Cyano-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-2-dimethylamino-acetamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound D2 and N,N-dimethylglycine. 
     LCMS: m/z 500 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 231 
     Compound E1 
     6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.0 g, 9.791 mmol) was dissolved in CH 3 CN (40 mL), added with NBS (1.92 g, 1.1 eq.), and the mixture was stirred at room temperature for 2.5 hr. The reaction solution was added to water (40 mL), and the precipitated solid was filtered to obtain the title compound (white powder, 2.55 g, 92%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.36 (1H, s), 6.84 (1H, s), 3.91 (3H, s), 3.02 (2H, t, J=6.8 Hz), 2.66 (2H, t, J=6.8 Hz), 1.42 (6H, s). 
     LCMS: m/z 283, 285 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition S) 
     Example 232 
     Compound E2-1 
     9-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 7.89 g, 27.85 mmol) and 3-hydrazino-benzonitrile (4.45 g, 1.2 eq.) were dissolved in TFA (250 mL), and stirred at 100° C. for 2 hr. TFA was removed under reduced pressure and the residues were added with saturated aqueous solution of NaHCO 3  (500 mL), followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with ethyl acetate. After stirring at room temperature, the precipitated solid was separated by filtration (Compound E2-2). The filtrate was concentrated under reduced pressure to obtain the title compound as a mixture with E2-2 (yellowish white powder, 2.65 g). 
     LCMS: m/z 381, 383 [M+H] +   
     HPLC retention time: 3.03 min (analysis condition S) 
     Example 233 
     Compound E2-2 
     9-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound E2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 11.70 (1H, s), 7.69 (1H, dd, J=8.1, 0.8 Hz), 7.55 (1H, s), 7.48 (1H, dd, J=7.4, 0.8 Hz), 7.27 (1H, s), 7.22 (1H, dd, J=8.1, 7.4 Hz), 4.23 (2H, s), 3.91 (3H, s), 1.70 (6H, s). 
     LCMS: m/z 381, 383 [M+H] +   
     HPLC retention time: 2.92 min (analysis condition S) 
     Example 234 
     Compound E2-3, Compound E2-4 
     3,9-Dibromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     1,9-Dibromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared (as a mixture) from Compound E1. 
     Example 235 
     Compound E3-1-1 
     9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound E2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.82 (1H, s), 8.30 (2H, s+d), 8.03 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.49 (1H, s), 4.04 (3H, s), 1.81 (6H, s). 
     LCMS: m/z 395, 397 [M+H] +   
     HPLC retention time: 2.77 min (analysis condition S) 
     Example 236 
     Compound E3-1-2 
     9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound E3-1-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.84 (1H, s), 8.31 (1H, s), 7.86 (1H, dd, J=8.2, 0.9 Hz), 7.70 (1H, d, J=7.1 Hz), 7.47 (1H, s), 7.43 (1H, t, J=7.8 Hz), 4.04 (3H, s), 1.81 (6H, s). 
     LCMS: m/z 395, 397 [M+H] +   
     HPLC retention time: 2.42 min (analysis condition S) 
     Example 237 
     Compound E3-1-3 
     3,9-Dibromo-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound E2-3 and Compound E2-4 (mixture). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.42 (1H, s), 8.28 (1H, s), 8.09 (1H, d, J=8.2 Hz), 7.68 (1H, d, J=1.6 Hz), 7.47 (1H, s), 7.39 (1H, dd, J=8.3, 1.7 Hz), 4.03 (3H, s), 1.78 (6H, s). 
     LCMS: m/z 448, 450, 452 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition S) 
     Example 238 
     Compound E3-2 
     9-Bromo-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 1.0 g, 2.53 mmol) was dissolved in NMP (10 mL), added with NaOMe (683 mg, 5 eq.) and 1-dodecanethiol (3.0 mL, 5 eq.), and stirred at 160° C. for 1 hr. The reaction solution was added to 0.5 N aqueous solution of hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with MeOH, and the solid remaining after dissolution was filtered to obtain the title compound (yellow powder, 1.88 g, 65%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.77 (1H, s), 11.13 (1H, d, J=2.4 Hz), 8.31 (1H, dd, J=7.9, 2.4 Hz), 8.25 (1H, d, J=3.0 Hz), 8.01 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.28 (1H, d, J=2.4 Hz), 1.74 (6H, s). 
     LCMS: m/z 381, 383 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition S) 
     Example 239 
     Compound E3-3 
     9-Bromo-8-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound E3-2 and 2-bromopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.77 (1H, s), 8.29 (2H, s+d), 8.01 (1H, s), 7.60 (1H, d, J=8.1 Hz), 7.50 (1H, s), 5.03 (1H, m), 1.79 (6H, s), 1.36 (6H, d, J=5.9 Hz). 
     LCMS: m/z 423, 425 [M+H] +   
     HPLC retention time: 2.98 min (analysis condition S) 
     Example 240 
     Compound E4-1 
     8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound E3-1-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.88 (1H, br. s), 8.43 (1H, s), 8.30 (1H, d, J=8.2 Hz), 8.05 (1H, d, J=0.5 Hz), 7.65-7.62 (2H, m), 4.11 (3H, s), 1.84 (6H, s). 
     LCMS: m/z 342 [M+H] +   
     HPLC retention time: 2.23 min (analysis condition S) 
     Example 241 
     Compound E4-2-1 
     9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 50 mg, 0.13 mmol), bis (acetonitrile)dichloropalladium (II) (1.64 mg, 0.05 eq.), XPhos (9.05 mg, 0.15 eq.), cesium carbonate (185 mg, 4.5 eq.) and 3-methyl-1-butyn-1-ol (18.6 μl, 1.5 eq.) were dissolved in acetonitrile and stirred at 85° C. for 2 hr. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (brown solid, 21.3 mg, 42%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=8.1 Hz), 8.11 (1H, s), 8.00 (1H, s), 7.57 (1H, d, J=8.1 Hz), 7.40 (1H, s), 5.50 (1H, s), 3.95 (3H, s), 2.54 (1H, s), 1.79 (6H, s), 1.49 (6H, s). 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition S) 
     Example 242 
     Compound E4-2-2 
     9-Ethynyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2-1, 21.3 mg, 0.05 mmol) and sodium hydride (3.2 mg, 1.5 eq.) were dissolved in THF, and the mixture was stirred overnight at 50° C. Water was added to the reaction solution and the residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (brown solid, 9.6 mg, 31%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.26 (1H, d, J=8.2 Hz), 8.16 (1H, s), 7.97 (1H, s), 7.53 (1H, d, J=8.2 Hz), 7.41 (1H, s), 4.32 (1H, s), 4.00 (3H, s), 1.79 (6H, s). 
     LCMS: m/z 341 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition S) 
     Example 243 
     Compound E4-3 
     8-Methoxy-6,6-dimethyl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 50 mg, 0.13 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (1:1) (10.3 mg, 0.1 eq.), TEA (53 μl, 3 eq.) and potassium vinyltrifluoroborate (51 mg, 3 eq.) were dissolved in n-propanol and the mixture was stirred at 60° C. for 5 days. The reaction solution was added to water and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (brown powder, 25 mg, 19%). 
     LCMS: m/z 343 [M+H] +   
     HPLC retention time: 2.55 min (analysis condition S) 
     Example 244 
     Compound E4-4 
     9-(2-Diethylamino-ethylsulfanyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound E3-1-1. 
     LCMS: m/z 448 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition U) 
     Example 245 
     Compound E4-5 
     9-Isopropylsulfanyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound E3-1-1 and sodium salt of propane-2-thiol. 
     LCMS: m/z 391 [M+H] +   
     HPLC retention time: 2.98 min (analysis condition U) 
     Example 246 
     Compound E4-6 
     8-Methoxy-6,6-dimethyl-9-(4-methylpiperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound E3-1-1 and 1-methylpiperazine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.25 (1H, d, J=7.8 Hz), 7.93 (1H, s), 7.65 (1H, s), 7.50 (1H, d, J=6.8 Hz), 7.25 (1H, s), 3.93 (3H, s), 3.02 (4H, br), 2.22 (3H, s), 1.73 (6H, s). 
     LCMS: m/z 415 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition U) 
     Example 247 
     Compound E4-7-1 
     4-(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     To 9-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 300 mg, 0.759 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (282 mg, 0.911 mmol, 1.2 eq.), Pd(PPh 3 ) 2 Cl 2  (26.6 mg, 0.0379 mmol, 0.05 eq.) and sodium carbonate (241 mg, 2.28 mmol, 3.0 eq.), DME (5 ml) and water (1 ml) were added. The mixture was subjected to reduced pressure under ultrasonication treatment, followed by flushing with nitrogen gas. This procedure was repeated five times and then degassed. The mixture was stirred at 80° C. for 80 min under nitrogen atmosphere. Pd(PPh 3 ) 2 Cl 2  (26.6 mg, 0.0379 mmol, 0.05 eq.) was added and the mixture was further stirred at 80° C. for 20 min. Then, the mixture was cooled to room temperature, and added with water and ethyl acetate. The insoluble matters were filtered through Celite. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration, followed by concentration under reduced pressure to obtain the title compound as a crude product (gray powder). 
     LCMS: m/z 498 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition S) 
     Example 248 
     Compound E4-7-2 
     8-Methoxy-6,6-dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-4-1. 
     LCMS: m/z 368 [M+H] +   
     HPLC retention time: 1.27 min (analysis condition S) 
     Example 249 
     Compound E4-8-1 
     4-(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound B4-7-1. 
     LCMS: m/z 500 [M+H] +   
     HPLC retention time: 4.18 min (analysis condition W) 
     Example 250 
     Compound E4-8-2 
     8-Methoxy-6,6-dimethyl-11-oxo-9-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-8-1. 
     LCMS: m/z 400 [M+H] +   
     HPLC retention time: 1.35 min (analysis condition S) 
     Example 251 
     Compound E4-9-1 
     4-(3-Cyano-8-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound E3-3. 
     LCMS: m/z 526 [M+H] +   
     HPLC retention time: 3.13 min (analysis condition S) 
     Example 252 
     Compound E4-9-2 
     8-Isopropoxy-6,6-dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound E4-9-1. 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 1.40 min (analysis condition S) 
     Example 253 
     Compound E4-10 
     9-Cyclopropyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound E3-1-1 and potassium cyclopropyltrifluoroborate. 
     LCMS: m/z 357 [M+H] +   
     HPLC retention time: 2.62 min (analysis condition S) 
     Example 254 
     Compound E4-11 
     3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-28, the title compound was prepared from Compound E3-1-1. 
     LCMS: m/z 361 [M+H] +   
     HPLC retention time: 1.68 min (analysis condition S) 
     Example 255 
     Compound E5-1 
     9-Ethyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The ethyl acetate suspension of 8-methoxy-6,6-dimethyl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-3, 25 mg, 0.07 mmol) and palladium carbon (25 mg) were stirred at room temperature for 1 hr under hydrogen atmosphere. The reaction solution was filtered through Celite. The filtrate was concentrated under reduced pressure and the resulting residues were purified by high performance liquid chromatography to obtain the title compound (white solid, 3.2 mg, 13%). 
     LCMS: m/z 345 [M+H] +   
     HPLC retention time: 2.62 min (analysis condition S) 
     Example 256 
     Compound E5-2 
     9-(2-Diethylamino-ethanesulfonyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound E4-4. 
     LCMS: m/z 480 [M+H] +   
     HPLC retention time: 1.97 min (analysis condition U) 
     Example 257 
     Compound E5-3 
     8-Methoxy-6,6-dimethyl-11-oxo-9-(propane-2-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound E4-5. 
     LCMS: m/z 423 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition U) 
     Example 258 
     Compound E5-4 
     9-(1-Isopropyl-piperidin-4-yl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-8-2 and acetone. 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition S) 
     Example 259 
     Compound E5-5 
     8-Methoxy-6,6-dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-7-2 and oxetan-3-one. 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 1.32 min (analysis condition S) 
     Example 260 
     Compound E5-6 
     8-Isopropoxy-6,6-dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-9-2 and oxetan-3-one. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.71 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.94 (1H, s), 7.58 (1H, d, J=7.6 Hz), 7.33 (1H, s), 5.84 (1.0H, m), 4.95 (1H, m), 4.56 (4H, dt, J=17.4, 6.3 Hz), 3.56 (1H, m), 3.01 (2H, br), 1.78 (6H, s), 1.34 (6H, d, J=5.9 Hz). 
     LCMS: m/z 482 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 261 
     Compound E5-7 
     9-(4-Isopropyl-piperazin-1-carbonyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound E4-11 and 1-isopropylpiperazine. 
     LCMS: m/z 471 [M+H] +   
     HPLC retention time: 1.18 min (analysis condition S) 
     Example 262 
     Compound E5-8 
     8-Methoxy-6,6-dimethyl-9-(morpholine-4-carbonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound E4-11 and morpholine. 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 1.68 min (analysis condition S) 
     Example 263 
     Compound E6-1 
     (3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propionic acid methyl ester 
     
       
         
         
             
             
         
       
     
     To the mixture of 9-ethynyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2, 27 mg, 0.079 mmol), palladium (II) chloride (2.0 mg, 0.14 eq.), copper (II) chloride (25.0 mg, 2.2 eq.), and sodium acetate (14.1 mg, 2.13 eq.), methanol (1.5 mL) was added, and then the mixture was stirred at room temperature for 2 days under carbon monoxide atmosphere. The mixture was extracted with water and ethyl acetate and the insoluble matters were filtered off. The organic layer was washed with brine and dried over magnesium sulfate. The residues obtained after filtration and concentration under reduced pressure were washed with dichloromethane to obtain the title compound (13.9 mg, 44%). 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 2.81 min (analysis condition F) 
     Example 264 
     Compound E6-2 
     (3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propynoic acid 
     
       
         
         
             
             
         
       
     
     (3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propynoic acid methyl ester (Compound E6-1, 15.2 mg, 0.038 mmol) was dissolved in a mixture solvent of methanol (1.5 mL) and THF (0.5 mL), added with 2 N aqueous solution of potassium hydroxide (5 drops), and then stirred at room temperature overnight. 0.5 N Hydrochloric acid was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solids obtained after filtration and concentration under reduced pressure were washed with dichloromethane and purified by HPLC to obtain the title compound (white solid, 9.6 mg, 66%). 
     LCMS: m/z 385 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition F) 
     Example 265 
     Compound E6-3 
     9-(3-Hydroxy-3-methyl-butyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2-1, 21.0 mg, 0.0527 mmol) was dissolved in ethanol (15 mL) and N,N-dimethylacetamide (2 mL), added with 10% Pd/C (6.7 mg), and then stirred at room temperature overnight under hydrogen atmosphere. The reaction solution was filtered and concentrated under reduced pressure. The resulting residues were diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was washed with dichloromethane to obtain the title compound (yellow powder, 16.9 mg, 80%). 
     LCMS: m/z 403 [M+H] +   
     HPLC retention time: 5.39 min (analysis condition H) 
     Example 266 
     Compound F1-1 
     4-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound E3-2 and 4-trifluoromethanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 564, 566 [M+H] +   
     HPLC retention time: 3.30 min (analysis condition S) 
     Example 267 
     Compound F1-2 
     9-Bromo-6,6-dimethyl-11-oxo-8-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F1-1. 
     LCMS: m/z 464, 466 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 268 
     Compound F1-3 
     9-Bromo-8-(1-methanesulfonyl-piperidin-4-yl oxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F1-2 and methanesulfonyl chloride. 
     LCMS: m/z 542, 544 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition S) 
     Example 269 
     Compound F1-4 
     9-Bromo-6,6-dimethyl-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound E3-2 and tetrahydropyran-4-ol. 
     LCMS: m/z 465, 467 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition S) 
     Example 270 
     Compound F2 
     Trifluoro-methanesulfonic acid 9-bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound E3-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.99 (1H, s), 8.51 (1H, s), 8.31 (1H, dd, J=8.2, 0.7 Hz), 8.17 (1H, s), 8.07 (1H, s), 7.67 (1H, dd, J=8.2, 1.4 Hz), 1.81 (6H, s). 
     LCMS: m/z 513, 515 [M+H] +   
     HPLC retention time: 3.13 min (analysis condition S) 
     Example 271 
     Compound F3-1 
     9-Bromo-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F1-2 and oxetan-3-one. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, 8 Hz), 8.29 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8 Hz), 7.55 (1H, s), 5.00-4.95 (1H, m), 4.55 (2H, dd, 8, 8 Hz), 4.44 (2H, dd, 8, 8 Hz), 2.52-2.46 (1H, m), 2.33-2.29 (2H, m), 1.96-1.94 (2H, m), 1.79 (8H, br. s) 
     LCMS: m/z 519, 521 [M+H] +   
     HPLC retention time: 2.78 min (analysis condition W) 
     Example 272 
     Compound F3-2 
     9-Bromo-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 517, 519 [M+H] +   
     HPLC retention time: 1.70 min (analysis condition S) 
     Example 273 
     Compound F3-3 
     9-Bromo-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 1-methanesulfonylpiperazine. 
     LCMS: m/z 527, 529 [M+H] +   
     HPLC retention time: 2.48 min (analysis condition S) 
     Example 274 
     Compound F3-4 
     9-Bromo-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and morpholine. 
     LCMS: m/z 450, 452 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition S) 
     Example 275 
     Compound F3-5 
     9-Bromo-8-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 2-piperazin-1-yl ethanol. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.26 (2.0H, s+d), 7.97 (1H, s), 7.54 (1H, d, J=8.7 Hz), 7.43 (1H, s), 4.45 (1H, t, J=5.4 Hz), 3.55 (2H, q, J=5.8 Hz), 3.17 (4H, br), 2.66 (2H, br), 1.76 (6H, s). 
     LCMS: m/z 493, 495 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 276 
     Compound F3-6-1 
     [1-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-carbamic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperidin-4-yl-carbamic acid tert-butyl ester. 
     LCMS: m/z 563, 565 [M+H] +   
     HPLC retention time: 3.05 min (analysis condition S) 
     Example 277 
     Compound F3-6-2 
     8-(4-Amino-piperidin-1-yl)-9-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F3-6-1. 
     LCMS: m/z 463, 465 [M+H] +   
     HPLC retention time: 1.47 min (analysis condition S) 
     Example 278 
     Compound F3-7 
     9-Bromo-8-(4-hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperidin-4-ol. 
     LCMS: m/z 464, 466 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition S) 
     Example 279 
     Compound F3-8 
     9-Bromo-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 1-isopropylpiperazine. 
     LCMS: m/z 491, 493 [M+H] +   
     HPLC retention time: 1.58 min (analysis condition S) 
     Example 280 
     Compound F3-9 
     9-Bromo-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperazine. 
       1 H-NMR (DMSO-d 6 ) δ: 8.30-8.24 (2H, m), 8.00 (1H, s), 7.63-7.58 (1H, m), 7.37 (1H, s), 3.10-3.01 (4H, m), 2.91-2.85 (4H, m), 1.76 (6H, s) 
     LCMS: m/z 449, 451 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Example 281 
     Compound F3-10 
     4-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperazine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 549, 551 [M+H] +   
     HPLC retention time: 4.61 min (analysis condition W) 
     Example 282 
     Compound F3-11 
     9-Bromo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 4-piperidin-4-yl morpholine. 
       1 H-NMR (DMSO-d 6 ) δ: 8.30-8.24 (2H, m), 8.00 (1H, s), 7.59 (1H, d, J=8.2 Hz), 7.42 (1H, s), 3.66-3.45 (6H, m), 2.80 (2H, t, J=11.1 Hz), 2.38-2.28 (1H, m), 1.96-1.87 (2H, m), 1.75 (6H, s), 1.66-1.56 (2H, m) 
     LCMS: m/z 533, 535 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition S) 
     Example 283 
     Compound F4-1-1 
     9-Ethynyl-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, 8 Hz), 8.17 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8 Hz), 7.50 (1H, s), 4.87-4.83 (1H, m), 4.55 (2H, dd, 4, 4 Hz), 4.45 (2H, dd, 4, 4 Hz), 3.44 (1H, ddd, 4, 4, 4 Hz), 2.33-2.24 (2H, m), 1.99-1.91 (2H, m), 1.78 (8H, br. s) 
     LCMS: m/z 466 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition W) 
     Example 284 
     Compound F4-1-2 
     9-Ethyl-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F4-1-1. 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 2.74 min (analysis condition W) 
     Example 285 
     Compound F4-2 
     N-[1-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F3-6-2 and methanesulfonyl chloride. 
     LCMS: m/z 541, 543 [M+H] +   
     HPLC retention time: 2.37 min (analysis condition S) 
     Example 286 
     Compound F4-3 
     9-Bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and 1-oxetan-3-one. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.83 (1H, br. s), 8.31-8.32 (1H, m), 8.27-8.29 (1H, m), 8.01-8.04 (1H, m), 7.59-7.64 (1H, m), 7.48 (1H, s), 4.59 (2H, dd, J=6.3, 6.3 Hz), 4.48 (2H, dd, J=6.3, 6.3 Hz), 3.52 (1H, t, J=6.3 Hz), 3.12-3.25 (4H, m), 2.44-2.54 (4H, m), 1.78 (6H, s). 
     LCMS: m/z 505, 507 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Hydrochloric Acid Salt of Compound F4-3 
     9-Bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed by using ethanol comprising 25% water to obtain monohydrochloric acid salt of 9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.91 (1H, br.s), 11.70 (1H, br. s), 8.32-8.29 (2H, m), 8.04 (1H, s), 7.64-7.62 (1H, m), 7.52 (1H, s), 4.89-4.62 (4H, br. m), 3.66-3.39 (1H, m), 3.31-3.05 (8H, br. m), 1.81 (6H, s) 
     LCMS: m/z 505, 507 [M+H] +   
     Example 287 
     Compound F4-4 
     9-Bromo-8-{4-[2-(2-methoxy-ethoxy)-ethyl]-piperazin-1-yl}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F3-9 and 1-bromo-2-(2-methoxyethoxy)ethane. 
     LCMS: m/z 551, 553 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition W) 
     Example 288 
     Compound F4-5 
     9-Bromo-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-pyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and tetrahydropyran-4-one. 
     LCMS: m/z 533, 535 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition W) 
     Example 289 
     Compound F4-6 
     9-Bromo-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-thiopyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and tetrahydrothiopyran-4-one. 
     LCMS: m/z 549, 551 [M+H] +   
     HPLC retention time: 2.86 min (analysis condition W) 
     Example 290 
     Compound F4-7 
     9-Bromo-8-[4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound F4-6. 
     LCMS: m/z 581, 583 [M+H] +   
     HPLC retention time: 2.66 min (analysis condition W) 
     Example 291 
     Compound F4-8 
     9-Bromo-8-(4-cyclopropylmethyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F3-9 and bromomethylcyclopropane. 
     LCMS: m/z 503, 505 [M+H] +   
     HPLC retention time: 2.81 min (analysis condition W) 
     Example 292 
     Compound F4-9 
     9-Bromo-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and (1-ethoxy-cyclopropoxy)-trimethyl-silane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.22-8.30 (2H, m), 8.00 (1H, s), 7.56 (1H, d, J=7.9 Hz), 7.43 (1H, s), 3.30 (1H, d, J=5.8 Hz), 3.11 (4H, s), 2.75 (4H, s), 1.75 (6H, s), 0.47 (2H, d, J=5.8 Hz), 0.34 (2H, d, J=5.8 Hz) 
     LCMS: m/z 489, 491 [M+H] +   
     HPLC retention time: 1.68 min (analysis condition S) 
     Example 293 
     Compound F4-10 
     9-Bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.23-8.29 (2H, m), 8.00 (1H, s), 7.55 (1H, d, 7.9 Hz), 7.45 (1H, s), 4.04-4.15 (1H, m), 3.10-3.20 (4H, m), 2.39-2.48 (4H, m), 1.97-2.06 (2H, m), 1.78-1.88 (2H, m), 1.77 (6H, s), 1.61-1.72 (2H, m) 
     LCMS: m/z 503, 505 [M+H] +   
     HPLC retention time: 2.78 min (analysis condition W) 
     Example 294 
     Compound F5-1 
     9-Ethynyl-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-3. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 8.31 (1H, dd, J=8.1, 0.7 Hz), 8.19 (1H, s), 8.02 (1H, dd, J=1.4, 0.7 Hz), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.33 (1H, s), 4.55 (1H, s), 3.43 (4H, br), 2.98 (3H, s), 1.79 (6H, s). 
     LCMS: m/z 473 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition S) 
     Example 295 
     Compound F5-2 
     N-[1-(3-Cyano-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.98 (1H, s), 8.30 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.02 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.23 (2H, s+d), 4.55 (1H, s), 3.79 (2H, brd), 2.95 (4H, br), 1.96 (2H, brd), 1.78 (3H, s), 1.65 (2H, brd). 
     LCMS: m/z 487 [M+H] +   
     HPLC retention time: 2.15 min (analysis condition S) 
     Example 296 
     Compound F5-3 
     6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the target compound was prepared from Compound F3-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.33 (1H, d, J=1.3 Hz), 8.27 (1H, dd, J=7.7, 1.3 Hz), 8.00 (1H, s), 7.57 (1H, d, J=7.7 Hz), 7.40 (1H, s), 3.74 (2H, m), 3.19-3.33 (1H, m), 2.98-3.12 (2H, m), 2.35-2.62 (2H, m), 2.11-2.29 (2H, m), 1.89-2.06 (2H, m), 1.78 (6H, s), 1.54-1.70 (6H, m). 
     LCMS: m/z 464 [M+H] +   
     HPLC retention time: 1.55 min (analysis condition S) 
     Example 297 
     Compound F5-4 
     9-Ethynyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1 and Compound E4-2-2, the title compound was prepared from Compound F3-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=8.2 Hz), 8.14 (1H, s), 8.00 (1H, s), 7.58 (1H, dd, J=8.1, 1.3 Hz), 7.24 (1H, s), 4.50 (1H, s), 3.70-3.83 (2H, m), 3.34-3.48 (1H, m), 2.83-2.98 (2H, m), 2.45-2.58 (2H, m), 2.10-2.23 (2H, m), 1.90-2.03 (2H, m), 1.76 (6H, s), 1.51-1.74 (6H, m). 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 1.60 min (analysis condition S) 
     Example 298 
     Compound F5-5 
     9-Ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1 and Compound E4-2-2, the title compound was prepared from Compound F3-4. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.82 (1H, s), 8.31 (1H, d, J=7.9 Hz), 8.18 (1H, s), 8.02 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.28 (1H, s), 4.53 (1H, s), 3.80 (4H, s), 3.36 (4H, s), 1.79 (6H, s). 
     LCMS: m/z 396 [M+H] +   
     HPLC retention time: 2.32 min (analysis condition S) 
     Example 299 
     Compound F5-6 
     9-(3-Dimethylamino-prop-1-ynyl)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 3-dimethylaminopropyne. 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.52 (1H, d, J=7.8 Hz), 8.47 (1H, s), 7.76 (1H, s), 7.56 (1H, d, J=7.8 Hz), 7.03 (1H, s), 3.92 (4H, m), 3.55 (2H, s), 3.39 (4H, m), 2.37 (6H, s), 1.83 (6H, s) 
     LCMS: m/z 453 [M+H] +   
     Example 300 
     Compound F5-7 
     6,6-Dimethyl-8-morpholin-4-yl-9-(3-morpholin-4-yl-prop-1-ynyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To 9-bromo-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F3-4, 30 mg, 0.067 mmol), 3-bromopropyne (0.01 ml, 0.13 mmol), morpholine (0.029 ml, 0.33 mmol), X-Phos (4.8 mg, 15% mol), PdCl 2  (CH 3 CN) 2  (0.9 mg, 5% mol) and cesium carbonate (87 mg, 0.27 mmol), acetonitrile (2 ml) was added and the mixture was stirred at 80° C. for 2 hr. The reaction solution was added to water, and then extracted with dichloromethane. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (pale brown solid, 18 mg, 64%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=7.8 Hz), 8.14 (1H, s), 8.00 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.27 (1H, s), 3.79 (4H, m), 3.64 (4H, m), 3.61 (2H, s), 3.33 (4H, m), 2.56 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 495 [M+H] +   
     Example 301 
     Compound F5-8 
     6,6-Dimethyl-8-morpholin-4-yl-11-oxo-9-pent-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 1-pentyne. 
     LCMS: m/z 438 [M+H] +   
     HPLC retention time: 2.88 min (analysis condition S) 
     Example 302 
     Compound F5-9 
     9-(3-Methoxy-prop-1-ynyl)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 3-methoxypropyne. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, J=7.8 Hz), 8.15 (1H, s), 8.01 (1H, s), 7.60 (1H, d, J=7.8 Hz), 7.28 (1H, s), 4.41 (2H, s), 3.79 (4H, m), 3.37 (3H, s), 3.34 (4H, m), 1.78 (6H, s) 
     LCMS: m/z 440 [M+H] +   
     Example 303 
     Compound F5-10 
     9-[3-(4-Cyclopropyl-piperazin-1-yl)-prop-1-ynyl]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F3-4 and 3-bromopropyne and 4-cyclopropylpiperazine. 
     LCMS: m/z 534 [M+H] +   
     HPLC retention time: 1.40 min (analysis condition S) 
     Example 304 
     Compound F5-11 
     6,6-Dimethyl-9-(1-methyl-1H-pyrazol-4-yl)-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-4 and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=7.8 Hz), 8.22 (1H, s), 8.09 (1H, s), 7.99 (1H, s), 7.95 (1H, s), 7.56-7.61 (1H, m), 7.36 (1H, s), 3.90 (3H, s), 3.73 (4H, s), 2.95 (4H, s), 1.77 (6H, s). 
     LCMS: m/z 452 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition U) 
     Example 305 
     Compound F5-12 
     9-Cyclopropyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-4 and potassium cyclopropyltrifluoroborate. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.45 (1H, d, J=7.8 Hz), 7.83 (2H, m), 7.54 (1H, d, J=7.8 Hz), 7.20 (1H, s), 3.96 (4H, m), 3.24 (4H, m), 2.25 (1H, m), 1.80 (6H, s), 1.09 (2H, m), 0.93 (2H, m) 
     LCMS: m/z 412 [M+H] +   
     Example 306 
     Compound F5-13 
     6,6-Dimethyl-8-morpholin-4-yl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-24, the title compound was prepared from Compound F3-4 and potassium vinyltrifluoroborate. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition U) 
     Example 307 
     Compound F5-14 
     9-Ethynyl-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-8. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.73 (1H, s), 8.31 (1H, d, J=9.1 Hz), 8.16 (1H, d, J=1.2 Hz), 8.00 (1H, s), 7.60 (1H, d, J=7.9 Hz), 7.25 (1H, s), 4.50 (1H, d, J=1.8 Hz), 2.72 (1H, m), 2.65 (4H, s), 1.78 (6H, s), 1.04 (6H, d, J=5.5 Hz). 
     LCMS: m/z 437 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition S) 
     Example 308 
     Compound F5-15-1 
     4-(3-Cyano-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-10 and potassium cyclopropyltrifluoroborate. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.55 (1H, s), 8.28-8.25 (1H, m), 7.98-7.95 (1H, m), 7.62 (1H, s), 7.32 (1H, s), 3.56-3.53 (4 h, m), 3.09-3.07 (4H, m), 2.22-2.18 (1H, m), 1.73 (6H, br s), 1.44 (9H, s), 1.08-1.05 (2H, m), 0.77-0.76 (2H, m) 
     LCMS: m/z 511 [M+H] +   
     HPLC retention time: 4.50 min (analysis condition W) 
     Example 309 
     Compound F5-15-2 
     9-Cyclopropyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F5-15-1. 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition W) 
     Example 310 
     Compound F5-16 
     9-Ethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-3. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.77 (1H, br. s), 8.31 (1H, d, J=8.2 Hz), 8.16 (1H, s), 8.02 (1H, s), 7.61 (1H, dd, J=8.2, 1.3 Hz), 7.27 (1H, s), 4.59 (2H, dd, J=6.6, 6.6 Hz), 4.51 (1H, s), 4.49 (2H, dd, J=6.6, 6.6 Hz), 3.51 (1H, t, J=6.6 Hz), 3.35-3.43 (4H, m), 2.43-2.50 (4H, s), 1.78 (6H, s). 
     LCMS: m/z 451 [M+H] +   
     HPLC retention time: 1.40 min (analysis condition S) 
     Example 311 
     Compound F5-17 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound F4-3. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.84 (1H, br. s), 8.36 (1H, s), 8.32-8.29 (1H, d, 8.08 Hz), 8.04 (1H, s), 7.65-7.62 (1H, d, 8.08 Hz), 7.44 (1H, s), 4.62-4.57 (2H, m), 4.52-4.47 (2H, m), 3.81-3.78 (2H, t, 4.61 Hz), 3.57-3.50 (1H, m), 3.43 (4H, m) 2.51 (4H, m), 1.80 (6H, s) 
     LCMS: m/z 452 [M+H] +   
     Example 312 
     Compound F5-18 
     9-(3-Methoxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-methoxypropyne. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.77 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.13 (1H, s), 8.01 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.27 (1H, s), 4.62-4.57 (2H, m), 4.52-4.47 (2H, m), 4.39 (2H, s), 3.53-3.47 (1H, m), 3.38 (4H, m), 3.36 (3H, s), 2.51 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 495 [M+H] +   
     Example 313 
     Compound F5-19 
     9-(3-Dimethylamino-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and dimethyl-prop-2-ynylamine. 
     LCMS: m/z 508 [M+H] +   
     HPLC retention time: 1.07 min (analysis condition S) 
     Example 314 
     Compound F5-20 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-9-[3-(4-oxetan-3-yl-piperazin-1-yl)-prop-1-ynyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F4-3, 3-bromopropyne and 4-oxetan-3-yl-piperazine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.30 (1H, d, J=7.8 Hz), 8.12 (1H, s), 8.00 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.26 (1H, s), 4.60-4.42 (8H, m), 3.61 (2H, s), 3.60-3.30 (6H, m), 2.60-2.30 (12H, m), 1.77 (6H, s) 
     LCMS: m/z 605 [M+H] +   
     Example 315 
     Compound F5-21 
     9-Cyclopentylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and cyclopentylacetylene. 
     LCMS: m/z 519 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition S) 
     Example 316 
     Compound F5-22 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and propyne. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.37 (1H, d, J=8.2 Hz), 8.18 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=8.2 Hz), 7.19 (1H, s), 4.70-4.77 (2H, m), 4.62-4.68 (2H, m), 3.57-3.63 (1H, m), 3.38-3.45 (4H, m), 2.54-2.61 (4H, m), 2.10 (3H, s), 1.79 (6H, s) 
     LCMS: m/z 465 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition U) 
     Example 317 
     Compound F5-23 
     9-(3-Hydroxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the TMS complex of the title compound was prepared from Compound F4-3 and trimethylprop-2-ynyloxysilane. By treating the resulting TMS complex with tetrabutylammonium fluoride, the title compound was obtained. 
     LCMS: m/z 481 [M+H] +   
     HPLC retention time: 1.30 min (analysis condition S) 
     Example 318 
     Compound F5-24 
     6,6-Dimethyl-9-(4-methyl-pent-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 4-methylpent-1-yne. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.75 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.62-7.59 (1H, m), 7.23 (1H, s), 4.61-4.57 (2H, m), 4.51-4.46 (2H, m), 3.51-3.47 (1H, m), 3.37 (4H, m), 2.46 (4H, m), 2.41-2.39 (2H, d, 5.94 Hz), 1.92-1.80 (1H, m), 1.77 (6H, s), 1.04 (3H, s), 1.01 (3H, s) 
     LCMS: m/z 507 [M+H] +   
     Example 319 
     Compound F5-25 
     9-Cyclopropylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and ethynylcyclopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.74 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.05 (1H, s), 8.00 (1H, s), 7.62-7.58 (1H, m), 7.21 (1H, s), 4.62-4.57 (2H, m), 4.51-4.47 (2H, m), 3.53-3.48 (1H, m), 3.34 (4H, m), 2.46 (4H, m), 1.76 (6H, s), 1.64-1.58 (1H, m), 0.97-0.89 (2H, m), 0.76-0.70 (2H, m) 
     LCMS: m/z 491 [M+H] +   
     Example 320 
     Compound F5-26 
     6,6-Dimethyl-9-(3-morpholin-4-yl-prop-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F4-3, 3-bromopropyne and morpholine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=7.8 Hz), 8.13 (1H, s), 8.02 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.25 (1H, s), 4.61-4.48 (4H, m), 3.64-3.32 (11H, m), 2.60-2.40 (8H, m), 1.78 (6H, s) 
     LCMS: m/z 550 [M+H] +   
     Example 321 
     Compound F5-27 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-pent-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 1-pentyne. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.72 (1H, br. s), 8.28 (1H, d, 8.1 Hz), 8.06 (1H, s), 7.98 (1H, s), 7.58 (1H, d, 8.1 Hz), 7.21 (1H, s), 4.60-4.43 (4H, m), 3.53-3.44 (1H, m), 3.39-3.32 (2H, m), 1.75 (6H, s), 1.60-1.53 (4H, m), 1.01 (3H, t, 7.3 Hz) 
     LCMS: m/z 493 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition U) 
     Example 322 
     Compound F5-28 
     6,6-Dimethyl-9-(5-methyl-hex-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 5-methylhex-1-yne. 
     LCMS: m/z 521 [M+H] +   
     HPLC retention time: 2.37 min (analysis condition U) 
     Example 323 
     Compound F5-29 
     9-(3-Diethylamino-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-diethylaminopropyne. 
     LCMS: m/z 536 [M+H] +   
     HPLC retention time: 1.13 min (analysis condition S) 
     Example 324 
     Compound F5-30 
     9-[3-(Benzyl-ethyl-amino)-prop-1-ynyl]-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-benzyl-3-ethylaminopropyne. 
     LCMS: m/z 584 [M+H] +   
     HPLC retention time: 1.32 min (analysis condition S) 
     Example 325 
     Compound F5-31 
     9-[3-(1,1-Dioxo-1λ6-thiomorpholin-4-yl)-prop-1-ynyl]-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-propyne. 
     LCMS: m/z 598 [M+H] +   
     HPLC retention time: 1.35 min (analysis condition S) 
     Example 326 
     Compound F5-32 
     9-Isopropenyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-3 and 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.44 (1H, d, J=7.8 Hz), 8.09 (1H, s), 7.83 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.18 (1H, s), 5.24-5.20 (2H, m), 4.81-4.68 (4H, m), 3.66 (1H, m), 3.30 (4H, m), 2.57 (4H, m), 2.21 (3H, s), 1.82 (6H, s) 
     LCMS: m/z 467 [M+H] +   
     Example 327 
     Compound F5-33 
     6,6,9-Trimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F4-3. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.71 (1H, br. s), 8.33-8.31 (1H, d, 8.08 Hz), 8.01 (1H, s), 7.97 (1H, s), 7.62-7.59 (1H, m), 7.32 (1H, s), 4.61-4.57 (2H, m), 4.51-4.47 (2H, m), 3.55-3.49 (1H, m), 3.05 (4H, m), 2.47 (4H, m), 2.33 (3H, s), 1.76 (6H, s) 
     LCMS: m/z 441 [M+H] +   
     Example 328 
     Compound F5-34 
     9-Cyclopropyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-15-2 and oxetan-3-one. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.32-8.29 (1H, m), 8.00-7.99 (1H, m), 7.62-7.58 (2H, m), 7.32-7.31 (1H, m), 4.61-4.57 (2H, m), 4.52-4.49 (2H, m), 3.53 (1H, br. s), 3.18 (4H, br. s), 1.75 (6H, s), 1.25-1.23 (1H, m), 1.09-1.04 (2H, m), 0.79-0.75 (2H, m) 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 2.74 min (analysis condition W) 
     Example 329 
     Compound F5-35 
     6,6-Dimethyl-9-(1-methyl-1H-pyrazol-4-yl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-3 and 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole. 
     LCMS: m/z 507 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition U) 
     Example 330 
     Compound F5-36-1 
     4-[3-Cyano-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-2. 
     LCMS: m/z 621 [M+H] +   
     HPLC retention time: 2.58 min (analysis condition U) 
     Example 331 
     Compound F5-36-2 
     6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F5-36-1. 
     LCMS: m/z 520 [M+H] +   
     HPLC retention time: 1.82 min (analysis condition U) 
     Example 332 
     Compound F5-37 
     8-(4-Cyclopropyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-9. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.76 (1H, br. s), 8.31 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.01 (1H, s), 7.61 (1H, dd, J=8.1, 1.5 Hz), 7.24 (1H, s), 4.52 (1H, s), 3.28-3.36 (4H, m), 3.17 (1H, d, J=5.3 Hz), 2.70-2.77 (4H, m), 1.76 (6H, s), 0.47 (2H, d, J=5.3 Hz), 0.36 (2H, d, J=5.3 Hz). 
     LCMS: m/z 435 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition S) 
     Example 333 
     Compound F5-38 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-9 and propyne. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.76 (1H, br. s), 8.31-8.28 (1H, d, 8.08 Hz), 8.06 (1H, s), 8.00 (1H, s), 7.60-7.57 (1H, m), 7.19 (1H, s), 3.29 (4H, m), 2.74 (4H, m), 2.55 (1H, m), 2.13 (3H, s), 1.75 (6H, s), 0.51-0.43 (2H, m), 0.38-0.32 (2H, m) 
     LCMS: m/z 449 [M+H] +   
     Example 334 
     Compound F5-39 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-phenyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and phenylboric acid. 
     LCMS: m/z 487 [M+H] +   
     HPLC retention time: 2.15 min (analysis condition U) 
     Example 335 
     Compound F5-40 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-pyridin-3-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and pyridine-3-boric acid. 
     LCMS: m/z 488 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition U) 
     Example 336 
     Compound F5-41 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-thiophene-2-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and thiophene-2-boric acid. 
     LCMS: m/z 493 [M+H] +   
     HPLC retention time: 2.13 min (analysis condition U) 
     Example 337 
     Compound F5-42 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6,9-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F4-9. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.71 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.96 (1H, s), 7.61-7.58 (1H, m), 7.29 (1H, s), 2.97 (4H, m), 2.73 (4H, m), 2.56 (1H, m), 2.34 (3H, s), 1.76 (6H, s), 1.64-1.58 (1H, m), 0.50-0.44 (2H, m), 0.37-0.32 (2H, m) 
     LCMS: m/z 425 [M+H] +   
     Example 338 
     Compound F5-43 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the MeCN (8 ml) suspension of 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F4-10, 200 mg, 0.397 mmol), ethynyltriisopropylsilane (268 mg, 3.0 eq.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (Xphos) (39 mg, 0.2 eq.), Pd(CH 3 CN) 2 Cl 2  (11 mg, 0.1 eq.) and cesium carbonate (518 mg, 4.0 eq.) were added and the mixture was stirred and heated under reflux condition until the reaction is completed. Upon the completion of the reaction, distilled water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-[(triisopropylsilanyl)-ethynyl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (179 mg, 74%). 
     To the THF (6 ml) solution of the obtained compound (179 mg, 0.295 mmol), 1 M THF solution (710 l) of tetrabutylammonium fluoride was added and the mixture was stirred until the reaction is completed. Upon the completion of the reaction, ethyl acetate was added to the reaction solution, which was then washed with distilled water and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were washed with a mixture solvent of ethanol and distilled water to obtain the title compound (67 mg, 92%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.85 (1H, s), 8.31 (1H, d, 7.9 Hz), 8.20 (1H, s), 8.03 (1H, s), 7.62 (1H, d, 7.9 Hz), 7.35 (1H, s), 4.62 (1H, s), 3.94-4.03 (2H, m), 3.79-3.89 (1H, m), 3.48-3.54 (2H, m), 3.27-3.38 (2H, m), 2.96-3.16 (2H, m), 2.30-2.41 (2H, m), 2.16-2.26 (2H, m), 1.72-1.85 (8H, m) 
     LCMS: m/z 449 [M+H] +   
     HPLC retention time: 2.69 min (analysis condition W) 
     Example 339 
     Compound F5-44 
     8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-10 under propyne gas atmosphere. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.71 (1H, s), 8.30 (1H, d, 7.9 Hz), 8.06 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 7.9 Hz), 7.20 (1H, s), 2.75-2.83 (1H, m), 2.40-2.48 (4H, m), 2.11 (3H, s), 1.97-2.06 (2H, m), 1.76 (6H, s), 1.62-1.71 (2H, m) 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition W) 
     Example 340 
     Compound F5-45 
     9-Cyclobutylethynyl-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-10 and ethynylcyclobutane. 
     LCMS: m/z 503 [M+H] +   
     HPLC retention time: 1.85 min (analysis condition S) 
     Example 341 
     Compound F5-46 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-15-2 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.23 (1H, d, 8 Hz), 7.92 (1H, br. s), 7.59 (1H, s), 7.47 (1H, br. d, 8 Hz), 7.28 (1H, s), 3.12 (4H, br. s), 2.80 (1H, dddd, 8, 8, 8, 8 Hz), 2.20-2.13 (1H, m), 2.01 (2H, br. s), 1.86-1.68 (10H, m), 1.05 (2H, d, 8 Hz), 0.76 (2H, d, 4 Hz) 
     LCMS: m/z 465 [M+H] +   
     HPLC retention time: 2.79 min (analysis condition W) 
     Hydrochloric Acid Salt of Compound F5-46 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed by using ethanol comprising 25% water to obtain monohydrochloric acid salt of 8-(4-cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.81 (1H, s), 10.64 (1H, br. s), 8.32-8.29 (1H, m), 8.01 (1H, s), 7.67 (1H, s), 7.61-7.60 (1H, m), 7.33 (1H, s), 4.00-3.39 (6H, m), 3.28-3.02 (3H, m), 2.45-2.05 (5H, m), 1.83-1.77 (8H, m), 1.09-1.07 (2H, m), 0.81-0.80 (2H, m) 
     LCMS: m/z 465 [M+H] +   
     Example 342 
     Compound F5-47 
     8-(4-Cyclobutyl-piperazin-1-yl)-6,6,9-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the N,N-dimethyl formamide (1.5 ml) solution of 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F4-10, 50 mg, 0.099 mmol), trimethyl boroxine (12 mg, 0.1 eq.), tetrakis triphenylphosphine palladium (39 mg, 0.2 eq.), and potassium carbonate (41 mg, 3.0 eq.) were added, and the mixture was stirred at 100° C. for 24 hr. Upon the completion of the reaction, distilled water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the title compound (25 mg, 58%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.67 (1H, s), 8.31 (1H, d, 7.9 Hz), 7.98 (1H, s), 7.95 (1H, s), 7.59 (1H, d, 7.9 Hz), 7.30 (1H, s), 2.96-3.04 (4H, m), 2.76-2.84 (1H, m), 2.39-2.48 (4H, m), 2.32 (3H, s), 1.78-1.87 (2H, m), 1.75 (6H, s), 1.63-1.71 (2H, m) 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 2.66 min (analysis condition W) 
     Example 343 
     Compound F5-48 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropenyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-10 and 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane. 
     LCMS: m/z 465 [M+H] +   
     HPLC retention time: 1.63 min (analysis condition S) 
     Example 344 
     Compound F5-49 
     9-Ethynyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-11. 
     LCMS: m/z 479 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition U) 
     Example 345 
     Compound F5-50 
     6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-11 and propyne gas. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.40 (1H, d, J=7.8 Hz), 8.24 (1H, s), 7.84 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.14 (1H, s), 4.01-3.96 (2H, m), 3.78 (4H, m), 2.88-2.84 (2H, m), 2.68 (4H, m), 2.16-1.73 (5H, m), 2.16 (3H, s), 1.80 (6H, s) 
     LCMS: m/z 493 [M+H] +   
     Example 346 
     Compound F5-51 
     6,6,9-Trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F3-11 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.70 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.95 (1H, s), 7.61-7.58 (1H, m), 7.28 (1H, s), 3.60 (4H, m), 3.32-3.26 (2H, m), 2.79-2.69 (2H, m), 2.32 (3H, s), 1.95-1.90 (2H, m), 1.74 (6H, s), 1.65-1.52 (2H, m), 
     LCMS: m/z 469 [M+H] +   
     Methanesulfonic Acid Salt of Compound F5-51 
     6,6,9-Trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 2 N methanesulfonic acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed with ethanol to obtain methanesulfonic acid salt of 6,6,9-trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.72 (1H, br.s), 9.60 (1H, br. s), 8.33-8.31 (1H, d, 9.8 Hz), 8.01 (1H, s), 7.99 (1H, s), 7.61-7.59 (1H, m), 7.31 (1H, s), 4.07-4.04 (2H, m), 3.73-3.67 (2H, m), 3.55-3.40 (8H, m), 3.32-3.26 (1H, m), 2.70-2.60 (2H, m), 2.34 (3H, s), 2.30 (3H, s), 1.95-1.90 (2H, m), 1.75 (6H, s) 
     LCMS: m/z 469 [M+H] +   
     Example 347 
     Compound F6-1 
     9-(1-Isopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-36-2 and acetone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.68 (1H, br. s), 8.30 (1H, d, 8.1 Hz), 7.98 (1H, s), 7.82 (1H, s), 7.58 (1H, d, 8.1 Hz), 7.20 (1H, s), 5.85 (1H, s), 3.56-3.44 (2H, m), 3.21-3.14 (2H, m), 2.77-2.66 (5H, m), 2.12-2.09 (1H, m), 1.98-1.88 (2H, m), 1.74 (6H, s), 1.70-1.63 (1H, m), 1.58-1.45 (2H, m), 1.09-1.00 (6H, m) 
     LCMS: m/z 563 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition U) 
     Example 348 
     Compound F6-2 
     9-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F5-36-2. 
     LCMS: m/z 598 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 349 
     Compound F6-3 
     9-[3-(4-Cyclopropyl-piperazin-1-yl)-propyl]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-10. 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 1.32 min (analysis condition S) 
     Example 350 
     Compound F6-4 
     9-Ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-16. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.70 (1H, br. s), 8.29 (1H, d, 8.0 Hz), 8.03-7.94 (2H, m), 7.59-7.55 (1H, m), 7.38 (1H, s), 4.59-4.47 (4H, m), 3.53-5.47 (1H, m), 3.03-2.97 (2H, m), 2.73-2.62 (2H, m), 1.74 (6H, s), 1.29-1.98 (3H, m) 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition U) 
     Hydrochloric Acid Salt of Compound F6-4 
     9-Ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed with ethanol comprising 25% water to obtain monohydrochloric acid salt of 9-ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.83 (1H, br.s), 11.59 (1H, br. s), 8.33-8.31 (1H, m), 8.09 (1H, s), 8.02 (1H, s), 7.63-7.61 (1H, m), 7.39 (1H, s), 4.91-4.60 (4H, br. m), 3.58-3.40 (1H, m), 3.31-3.05 (8H, br. m), 2.73 (2H, q, J=7.3), 1.81 (6H, s), 1.29 (3H, t, J=7.3) 
     LCMS: m/z 455 [M+H] +   
     Example 351 
     Compound F6-5 
     9-(3-Methoxy-propyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-18. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.73 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.01 (1H, s), 8.00 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.42 (1H, s), 4.61-4.56 (2H, m), 4.51-4.46 (2H, m), 3.53-3.47 (1H, m), 3.42-3.37 (2H, m), 3.02 (4H, m), 2.75-2.68 (2H, m), 2.51 (4H, m), 1.93-1.82 (2H, m), 1.76 (6H, s) 
     LCMS: m/z 499 [M+H] +   
     Example 352 
     Compound F6-6 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-9-[3-(4-oxetan-3-yl-piperazin-1-yl)-propyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-20. 
     LCMS: m/z 609 [M+H] +   
     HPLC retention time: 1.00 min (analysis condition S) 
     Example 353 
     Compound F6-7 
     9-(2-Cyclopentyl-ethyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-21. 
     LCMS: m/z 523 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition S) 
     Example 354 
     Compound F6-8 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-22. 
       1 H-NMR (270 mHz DMSO-d 6 ) δ: 12.75 (1H, s), 8.30 (1H, d, J=8.2 Hz), 8.01-7.97 (2H, m), 7.59 (1H, d, J=7.1 Hz), 7.38 (1H, s), 4.51 (4H, dt, J=27.7, 6.3 Hz), 3.55-3.49 (1H, m), 3.02-2.96 (4H, m), 2.63 (2H, t, J=7.3 Hz), 2.47-2.41 (4H, m), 1.73 (6H, s), 1.70-1.61 (2H, m), 0.94 (3H, t, J=7.4 Hz). 
     LCMS: m/z 469 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition S) 
     Example 355 
     Compound F6-9 
     8-[4-(4-Hydroxy-butyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound F6-8. 
     LCMS: m/z 485 [M+H] +   
     HPLC retention time: 1.61 min (analysis condition S) 
     Example 356 
     Compound F6-10 
     9-(3-Hydroxy-propyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-23. 
     LCMS: m/z 499 [M+H] +   
     HPLC retention time: 1.42 min (analysis condition S) 
     Example 357 
     Compound F6-11 
     6,6-Dimethyl-9-(3-morpholin-4-yl-propyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-26. 
     LCMS: m/z 554 [M+H] +   
     HPLC retention time: 1.50 min (analysis condition U) 
     Example 358 
     Compound F6-12 
     6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-pentyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-27. 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition U) 
     Example 359 
     Compound F6-13 
     9-(3-Isopropoxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F5-23 and 2-bromopropane. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.40 (1H, d, J=7.8 Hz), 8.32 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=7.8 Hz), 7.18 (1H, s), 4.80-4.68 (4H, m), 4.46 (2H, s), 3.95 (1H, m), 3.64 (1H, m), 3.46 (4H, m), 2.62 (4H, m), 1.82 (6H, s), 1.24 (6H, d, J=7.0 Hz) 
     LCMS: m/z 523 [M+H] +   
     Example 360 
     Compound F6-14 
     9-Isopropyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-32. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.44 (1H, d, J=7.8 Hz), 8.27 (1H, s), 7.84 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.36 (1H, s), 4.82-4.70 (4H, m), 3.68 (1H, m), 3.45 (1H, m), 3.13-3.09 (4H, m), 2.64-2.62 (4H, m), 1.81 (6H, s), 1.31 (6H, d, J=7.0 Hz) 
     LCMS: m/z 469 [M+H] +   
     Example 361 
     Compound F6-15 
     8-(4-Cyclopropyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-37. 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition U) 
     Example 362 
     Compound F6-16 
     8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-38. 
     LCMS: m/z 453 [M+H] +   
     HPLC retention time: 1.63 min (analysis condition S) 
     Example 363 
     Compound F6-17 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-43. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.80 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.10 (1H, s), 8.02 (1H, s), 7.62 (1H, d, 7.9 Hz), 7.38 (1H, s), 3.78-3.88 (1H, m), 3.79-3.89 (1H, m), 3.48-3.54 (2H, m), 3.40-3.47 (2H, m), 3.30-3.39 (2H, m), 3.02-3.24 (4H, m), 2.73 (2H, q, 7.3 Hz), 2.30-2.41 (2H, m), 2.17-2.26 (2H, m), 1.71-1.86 (8H, m), 1.29 (3H, t, 7.3 Hz) 
     LCMS: m/z 453 [M+H] +   
     HPLC retention time: 2.76 min (analysis condition W) 
     Methanesulfonic Acid Salt of Compound F6-17 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved in 6 volumes of DMF at room temperature and added dropwise with aqueous solution of methanesulfonic acid (2 M, 1.05 eq.). The resulting solution was added dropwise to 60 volumes of acetonitrile, and the precipitated solid was filtered and dried to obtain monomethanesulfonic acid salt of 8-(4-cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.75 (1H, s), 8.31 (1H, J=8.4 Hz), 8.07 (1H, s), 8.01 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.38 (1H, s), 3.58-2.84 (10H, m), 2.71 (2H, q, J=7.5 Hz), 2.34 (3H, s), 2.20-2.04 (4H, m), 1.76-1.68 (8H, m), 1.26 (3H, t, J=7.5 Hz) 
     FABMS: m/z 453 [M+H] +   
     Example 364 
     Compound F6-18 
     8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-44. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.69 (1H, s), 8.31 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.99 (1H, s), 7.60 (1H, d, 7.9 Hz), 7.39 (1H, s), 2.92-3.02 (4H, m), 2.75-2.84 (1H, m), 2.65 (2H, t, 7.3 Hz), 2.38-2.48 (4H, m), 1.96-2.06 (2H, m), 1.78-1.87 (2H, m), 1.75 (6H, s), 1.62-1.73 (4H, m), 0.97 (3H, t, 7.3 Hz) 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 2.96 min (analysis condition W) 
     Example 365 
     Compound F6-19 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13, the title compound was prepared from Compound F5-48. 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 1.67 min (analysis condition S) 
     Example 366 
     Compound F6-20 
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-49. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.70 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.04 (1H, s), 8.00 (1H, s), 7.61 (1H, d, J=8.5 Hz), 7.34 (1H, s), 3.64-3.57 (4H, m), 3.27-3.18 (2H, m), 2.82-2.66 (4H, m), 2.39-2.28 (1H, m), 1.96-1.87 (2H, m), 1.76 (6H, s), 1.69-1.53 (2H, m), 1.29 (3H, t, J=7.3 Hz) 
     LCMS: m/z 483 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition U) 
     Hydrochloric Acid Salt of Compound F6-20 
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved in a mixture solution of methylethyl ketone (10 volumes), water (4 volumes) and acetic acid (3 volumes) at 60° C. To the dissolved solution, hydrochloric acid (2 N) was added dropwise (1 volume). After stirring at 60° C. for 30 min, ethanol (25 volume) was added dropwise. The precipitated solid was filtered and dried to obtain monohydrochloric acid salt of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 10.57 (1H, br. s), 8.30 (1H, J=8.4 Hz), 8.05 (1H, s), 7.99 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.36 (1H, s), 4.02-3.99 (2H, m), 3.84-3.78 (2H, m), 3.51-3.48 (2H, m), 3.15-3.13 (1H, s), 2.83-2.73 (2H, s), 2.71-2.67 (2H, s), 2.23-2.20 (2H, m), 1.94-1.83 (2H, m), 1.75 (6H, s), 1.27 (3H, t, J=7.5 Hz) 
     FABMS: m/z 483 [M+H] +   
     Example 367 
     Compound F6-21 
     6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-50. 
       1 H-NMR (270 MHz, CD 3 OD+CDCl 3 ) δ: 8.41 (1H, d, J=7.8 Hz), 8.14 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=7.8 Hz), 7.31 (1H, s), 3.77 (4H, m), 3.32 (2H, m), 2.86-2.66 (8H, m), 2.43-2.05 (3H, m), 1.79 (6H, s), 1.79-1.66 (4H, m), 1.02 (3H, t, J=7.3 Hz) 
     LCMS: m/z 497 [M+H] +   
     Example 368 
     Compound G2 
     8-Methoxy-10,10-dimethyl-10,11-dihydro-5H-1,11-diaza-benzo[B]fluorene 
     
       
         
         
             
             
         
       
     
     2-Hydrazinopyridine (1.3 g, 11.8 mmol) and 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.4 g, 11.8 mmol) were dissolved in NMP (60 mL), and stirred at 190° C. for 48 hr. The reaction solution was diluted with ethyl acetate, washed with water and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the target compound (white solid, 101 mg, 3%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 11.53 (1H, s), 8.16-8.12 (1H, m), 7.84 (1H, d, J=7.8 Hz), 7.23 (1H, d, J=8.4 Hz), 7.11 (1H, s), 7.03-6.98 (1H, m), 6.85-6.81 (1H, m), 3.96 (2H, s), 3.77 (3H, s), 1.64 (6H, s) 
     LCMS: m/z 279 [M+H] +   
     HPLC retention time: 2.08 min (analysis condition U) 
     Example 369 
     Compound G3 
     8-Methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound G2. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 12.95 (1H, br. s), 8.78 (1H, d, J=7.8 Hz), 8.52 (1H, d, J=4.9 Hz), 8.41 (1H, d, J=8.8 Hz), 7.37 (1H, dd, J=7.7, 5.0 Hz), 7.15 (1H, s), 7.04-7.00 (1H, m), 3.94 (3H, s), 1.98 (6H, s) 
     LCMS: m/z 293 [M+H] +   
     HPLC retention time: 2.13 min (analysis condition U) 
     Example 370 
     Compound G4 
     8-Hydroxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound G3. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 8.66 (1H, d, J=7.7 Hz), 8.29 (1H, d, J=4.9 Hz), 8.23 (1H, d, J=13.8 Hz), 7.29 (1H, dd, J=7.7, 5.0 Hz), 7.12 (1H, s), 6.93 (1H, d, J=8.6 Hz), 1.71 (6H, s) 
     LCMS: m/z 279 [M+H] +   
     HPLC retention time: 1.72 min (analysis condition U) 
     Example 371 
     Compound G5 
     Trifluoro-methanesulfonic acid 10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound G4. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 8.81 (1H, d, J=7.8 Hz), 8.60-8.52 (2H, m), 7.55 (1H, s), 7.46-7.40 (2H, m), 2.01 (6H, s) 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition U) 
     Example 372 
     Compound G6 
     10,10-Dimethyl-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound G5 and 4-pyrrolidin-1-yl-piperidine. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 13.12 (1H, s), 8.78 (1H, d, J=7.8 Hz), 8.49 (1H, d, J=4.9 Hz), 8.29 (1H, d, J=8.8 Hz), 7.34 (1H, dd, J=7.7, 5.0 Hz), 7.06-6.98 (2H, m), 3.96-3.88 (2H, m), 3.02-3.92 (2H, m), 2.69-2.60 (4H, m), 2.32-2.23 (1H, m), 2.09-2.00 (4H, m), 1.92 (6H, s), 1.26-1.19 (4H, m) 
     LCMS: m/z 415 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition U) 
     Example 373 
     Compound H1 
     6-Acetyl-7-methoxy-1,1-dimethyl-3,4-dihydro-TH-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     To the dichloromethane (70 ml) solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 3 g, 14.7 mmol), acetic anhydride (1.7 ml, 1.2 eq.) and aluminum chloride-nitrobenzene solution (1 M, 44 ml, 3 eq.) was added at 0° C., and stirred for 3 hr. Thereafter, the reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted twice with dichloromethane. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product. 
     Example 374 
     Compound H2-1 
     1-(3-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-ethanone 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound H1 and (3-bromo-phenyl)-hydrazine. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 3.97 min (analysis condition Y) 
     Example 375 
     Compound H2-2 
     1-(1-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-ethanone 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound H2-1. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 3.97 min (analysis condition Y) 
     Example 376 
     Compound H3 
     9-Acetyl-3-bromo-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound H2. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.80 (6H, s), 2.58 (3H, s), 4.06 (3H, s), 7.38 (1H, dd, 8.39 Hz, 1.91 Hz), 7.51 (1H, s), 7.67 (1H, bs, 1.53 Hz), 8.10 (1H, d, 8.39 Hz), 8.41 (1H, s), 12.3 (1H, s) 
     LCMS: m/z 412, 414 [M+H] +   
     HPLC retention time: 2.73 min (analysis condition U) 
     Example 377 
     Compound H4 
     9-Acetyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound H3. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.83 (6H, s), 2.58 (3H, s), 4.07 (3H, s), 7.53 (1H, s), 7.61 (1H, d, 8.01 Hz), 8.03 (1H, s), 8.31 (1H, d, 8.77 Hz), 8.42 (1H, s), 12.8 (1H, s). 
     LCMS: m/z 359 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition U) 
     Example 378 
     Compound H5 
     9-Acetyl-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound H4. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.77 (6H, s), 2.75 (3H, s), 7.43 (1H, s), 7.63 (1H, d, 8.01 Hz), 8.02 (1H, s), 8.32 (1H, d, 8.01 Hz), 8.67 (1H, s), 12.2 (1H, s), 12.8 (1H, s). 
     LCMS: m/z 345 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition S) 
     Example 379 
     Compound H6-1 
     9-Acetyl-6,6-dimethyl-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound H5 and tetrahydropyran-4-ol. 
     LCMS: m/z 429 [M+H] +   
     HPLC retention time: 2.48 min (analysis condition U) 
     Example 380 
     Compound H6-2 
     9-Acetyl-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound H5. 
     LCMS: m/z 444 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition U) 
     Example 381 
     Compound H7 
     Trifluoro-methanesulfonic acid 9-acetyl-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound H5. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.83 (6H, s), 2.74 (3H, s), 7.68 (1H, dd, 8.01 Hz, 1.53 Hz), 8.08 (2H, s), 8.33 (1H, d, 8.77 Hz), 8.79 (1H, s), 12.9 (1H, s). 
     Example 382 
     Compound H8-1 
     9-Acetyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and 4-pyrrolidin-1-yl-piperidine. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.65 (2H, m), 1.69 (4H, s), 1.79 (6H, s), 1.95 (2H, m), 2.18 (1H, m), 2.54 (4H, s), 2.59 (3H, s), 2.93 (2H, t, 11.8 Hz), 3.37 (2H, m), 7.36 (1H, s), 7.60 (1H, d, 8.01), 8.01 (1H, s), 8.13 (1H, s), 8.30 (1H, d, 8.39), 12.7 (1H, s). 
     LCMS: m/z 481 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition U) 
     Example 383 
     Compound H8-2 
     9-Acetyl-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7. 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 2.02 min (analysis condition U) 
     Example 384 
     Compound H8-3 
     9-Acetyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and morpholine. 
     LCMS: m/z 414 [M+H] +   
     HPLC retention time: 2.11 min (analysis condition S) 
     Example 385 
     Compound H8-4 
     9-Acetyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and 4-piperidin-4-yl-morpholine. 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Example 386 
     Compound H8-5 
     9-Acetyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and piperazine. 
     LCMS: m/z 413 [M+H] +   
     HPLC retention time: 1.71 min (analysis condition U) 
     Example 387 
     Compound H9-1 
     9-Acetyl-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound H8-5 and cyclobutanone. 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 1.82 min (analysis condition U) 
     Example 388 
     Compound H9-2 
     9-Acetyl-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-pyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound H8-5 and tetrahydropyran-4-one. 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 1.76 min (analysis condition U) 
     Example 389 
     Compound H9-3 
     9-Acetyl-8-[4-(1,1-dimethyl-prop-2-ynyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the anhydrous THF solution (0.5 mL) of 9-acetyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound H8-5, 25 mg, 0.06 mmol), 3-chloro-3-methyl-but-1-yne (0.013 mL, 0.12 mmol), copper (I) chloride (0.6 mg, 0.006 mmol) and triethylamine (0.017 mL, 0.12 mmol) were added at room temperature. After stirring for 30 min, the mixture was added with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by amino silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (white solid, 9.8 mg, 35%). 
     LCMS: m/z 479 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 390 
     Compound I1-1 
     6-Chloro-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 3.37 g, 16.5 mmol) was dissolved in CH 3 CN (82 mL), added with NCS (2.42 g, 1.1 eq.) and stirred at 90° C. for 1.5 hr. The reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed and the target compound was obtained after concentration under reduced pressure (yellow oily substance, 4.45 g). 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 7.16 (1H, s), 6.85 (1H, s), 3.90 (3H, s), 3.00 (2H, t, J=6.8 Hz), 2.65 (2H, t, J=6.8 Hz), 1.42 (6H, s). 
     LCMS: m/z 239 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition U) 
     Example 391 
     Compound I1-2 
     9-Chloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6-Chloro-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound I1-1, 4.45 g, 16.5 mmol) and 3-hydrazinobenzonitrile (2.63 g, 1.2 eq.) were dissolved in TFA (91 mL), and stirred at 90° C. for 3 hr. According to the concentration under reduced pressure, TFA was removed and the residues were added with saturated aqueous solution of NaHCO 3 , followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with ethyl acetate. After stirring at room temperature, the precipitated solid was separated by filtration. The filtrate was concentrated under reduced pressure to obtain the title compound as a mixture with I1-3 (red powder, 6.46 g). 
     Example 392 
     Compound I1-3 
     9-Chloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound I1-2. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 11.66 (1H, s), 7.65-7.69 (1H, m), 7.44-7.48 (1H, m), 7.39 (1H, s), 7.29 (1H, s), 7.17-7.23 (1H, m), 4.21 (2H, s), 3.91 (3H, s), 1.69 (6H, s). 
     LCMS: m/z 337 [M+H] +   
     HPLC retention time: 3.15 min (analysis condition U) 
     Example 393 
     Compound I2-1 
     2-(4-Chloro-3-methoxy-phenyl)-2-methyl-propionitrile 
     
       
         
         
             
             
         
       
     
     1-Chloro-4-fluoro-2-methoxy-benzene (4.3 g, 26.78 mmol) and isobutyronitrile (9.61 mL, 4.0 eq.) were dissolved in toluene (9.0 mL), added with KHMDS (80 mL, 0.5 M toluene solution) and stirred at 65° C. for 2 hr. The reaction solution was cooled to room temperature, added with aqueous solution of 1 N hydrochloric acid and then extracted with MTBE. The organic layer was washed with saturated brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.72 g, 31%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.37 (1H, d, J=8.4 Hz), 7.05 (1H, d, J=2.1 Hz), 6.97 (1H, dd, J=8.2, 2.1 Hz), 3.95 (3H, s), 1.73 (6H, s). 
     HPLC retention time: 2.33 min (analysis condition S) 
     Example 394 
     Compound I2-2 
     4-(4-Chloro-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K3, the title compound was prepared from Compound I2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 7.42 (1H, d, J=8.1 Hz), 6.92 (1H, d, J=2.1 Hz), 6.86 (1H, dd, J=8.2, 2.3 Hz), 4.01 (2H, q, J=7.1 Hz), 3.87 (3H, s), 3.43 (2H, s), 1.44 (6H, s), 1.12 (3H, t, J=7.2 Hz). 
     LCMS: m/z 299, 301 [M+H] +   
     HPLC retention time: 2.52, 3.05 min (analysis condition S) 
     Example 395 
     Compound I2-3 
     4-(4-Chloro-3-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K4, the title compound was obtained as a crude product from Compound I2-2. 
     Example 396 
     Compound I2-4 
     2-[1-(4-Chloro-3-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-TH-indole-3-carboxylic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K5, the title compound was obtained from Compound I2-3. 
     LCMS: m/z 397, 399 [M+H] +   
     HPLC retention time: 2.83 min (analysis condition S) 
     Example 397 
     Compound I3 
     9-Chloro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     (Method 1) Under the same conditions as the method for synthesizing Compound A4, the title compound was obtained from Compound I1-2. 
     (Method 2) Under the same conditions as the method for synthesizing Compound L8-1, the title compound was obtained from Compound I2-4. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.79 (1H, s), 8.27-8.31 (1H, m), 8.12 (1H, s), 8.00-8.02 (1H, m), 7.58-7.63 (1H, m), 7.51 (1H, s), 4.03 (3H, s), 1.80 (6H, s). 
     LCMS: m/z 351 [M+H] +   
     HPLC retention time: 2.87 min (analysis condition U) 
     Example 398 
     Compound I4 
     9-Chloro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound I3. 
     LCMS: m/z 337 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition U) 
     Example 399 
     Compound I5 
     Trifluoro-methanesulfonic acid 9-chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound I4. 
     LCMS: m/z 469 [M+H] +   
     HPLC retention time: 3.40 min (analysis condition U) 
     Example 400 
     Compound I6-1 
     9-Chloro-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 473 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition U) 
     Example 401 
     Compound I6-2 
     9-Chloro-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5. 
     LCMS: m/z 447 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition U) 
     Example 402 
     Compound I6-3 
     9-Chloro-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from 15 and morpholine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.79 (1H, s), 8.28 (1H, d, 8.0 Hz), 8.09 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 8.0 Hz), 7.45 (1H, s), 3.75-3.81 (4H, m), 3.13-3.19 (4H, m), 1.76 (6H, s) 
     LCMS: m/z 406 [M+H] +   
     HPLC retention time: 2.88 min (analysis condition U) 
     Example 403 
     Compound I6-4 
     9-Chloro-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 4-piperidin-4-yl-morpholine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.75 (1H, s), 8.28 (1H, d, 8.0 Hz), 8.07 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 8.0 Hz), 7.41 (1H, s), 3.55-3.62 (4H, m), 3.47-3.56 (4H, m), 2.75-2.86 (2H, m), 2.45-2.55 (4H, m), 2.28-2.39 (1H, m), 1.86-1.96 (2H, m), 1.76 (6H, s), 1.52-1.66 (2H, m) 
     LCMS: m/z 489 [M+H] +   
     HPLC retention time: 1.97 min (analysis condition U) 
     Example 404 
     Compound I6-5-1 
     [1-(9-Chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-carbamic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and piperidin-4-yl-carbamic acid tert-butyl ester. 
     LCMS: m/z 519 [M+H] +   
     HPLC retention time: 3.27 min (analysis condition U) 
     Example 405 
     Compound I6-5-2 
     8-(4-Amino-piperidin-1-yl)-9-chloro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound I6-5-1. 
     LCMS: m/z 419 [M+H] +   
     HPLC retention time: 2.12 min (analysis condition U) 
     Example 406 
     Compound I6-6 
     9-Chloro-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and piperazine. 
     LCMS: m/z 405 [M+H] +   
     HPLC retention time: 1.87 min (analysis condition U) 
     Example 407 
     Compound I7-1 
     N-[1-(9-Chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound I6-5-2. 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 2.62 min (analysis condition U) 
     Example 408 
     Compound I7-2 
     9-Chloro-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 1-oxetan-3-yl-piperazine. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 8.27-8.31 (1H, m), 8.07-8.09 (1H, s), 7.99-8.02 (1H, m), 7.59-7.62 (1H, m), 7.44-7.46 (1H, s), 4.54-4.60 (2H, m), 4.44-4.51 (2H, m), 3.47-3.55 (1H, m), 3.16-3.24 (4H, m), 2.40-2.55 (4H, m), 1.77 (6H, s) 
     LCMS: m/z 461 [M+H] +   
     HPLC retention time: 2.13 min (analysis condition U) 
     Example 409 
     Compound I7-3 
     9-Chloro-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 1-cyclopropylpiperazine. 
     LCMS: m/z 445 [M+H] +   
     HPLC retention time: 1.97 min (analysis condition U) 
     Example 410 
     Compound I7-4 
     9-Chloro-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound I6-6 and cyclobutanone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.78 (1H, s), 8.29 (1H, d, 8.5 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8.5 Hz), 7.44 (1H, s), 3.17-3.15 (4H, m), 2.83-2.76 (1H, m), 2.47-2.44 (4H, m), 2.04-1.97 (2H, m), 1.82 (2H, t, 9.8 Hz), 1.77 (6H, s), 1.70-1.63 (2H, m) 
     LCMS: m/z 459, 461 [M+H] +   
     HPLC retention time: 1.63 min (analysis condition S) 
     Example 411 
     Compound J2 
     6-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A2, the title compound was prepared from 6-methoxy-3,4-dihydro-TH-naphthalen-2-one and iodomethane. 
     LCMS: m/z 205 [M+H] +   
     HPLC retention time: 1.54 min (analysis condition S) 
     Example 412 
     Compound J3-1 
     9-Methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared from Compound J2 and 3-hydrazino-benzonitrile. 
     LCMS: m/z 303 [M+H] +   
     HPLC retention time: 2.73 min (analysis condition S) 
     Example 413 
     Compound J3-2 
     9-Methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile 
     
       
         
         
             
             
         
       
     
     Compound J3-2 was obtained as a by-product of the synthesis of Compound J3-1. 
     LCMS: m/z 303 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition S) 
     Example 414 
     Compound J4 
     9-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound J3-1 and Compound J3-2 (mixture). 
       1 H-NMR (DMSO-d 6 ) δ: 12.79 (1H, s), 8.33 (1H, d, J=8.2 Hz), 8.02 (1H, s), 7.81 (1H, d, J=8.6 Hz), 7.69 (1H, d, J=3.0 Hz), 7.63 (1H, dd, J=8.3, 1.4 Hz), 7.28 (1H, dd, J=8.7, 3.0 Hz), 3.87 (3H, s), 1.74 (6H, s). 
     LCMS: m/z 317 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition S) 
     Example 415 
     Compound J5 
     9-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound J4. 
       1 H-NMR (DMSO-d 6 ) δ: 12.75 (1H, s), 9.77 (1H, s), 8.32 (1H, dd, J=8.2, 0.7 Hz), 8.01 (1H, s), 7.68 (1H, d, J=8.6 Hz), 7.62 (1H, dd, J=8.2, 1.4 Hz), 7.58 (1H, d, J=2.8 Hz), 7.10 (1H, dd, J=8.6, 2.8 Hz), 1.72 (6H, s). 
     LCMS: m/z 303 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition S) 
     Example 416 
     Compound J6 
     Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound J5. 
       1 H-NMR (DMSO-d 6 ) δ: 12.95 (1H, s), 8.31 (1H, d, J=8.2 Hz), 8.15 (2H, m), 8.05 (1H, s), 7.87 (1H, dd, J=9.0, 2.7 Hz), 7.65 (1H, d, J=8.2 Hz), 1.80 (6H, s). 
     LCMS: m/z 435 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition S) 
     Example 417 
     Compound J7-1 
     9-Isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J4 and isopropanol. 
     LCMS: m/z 345 [M+H] +   
     HPLC retention time: 3.87 min (analysis condition W) 
     Example 418 
     Compound J7-2-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J5. 
     LCMS: m/z 486 [M+H] +   
     HPLC retention time: 4.15 min (analysis condition W) 
     Example 419 
     Compound J7-2-2 
     6,6-Dimethyl-11-oxo-9-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J7-2-1. 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 2.48 min (analysis condition W) 
     Example 420 
     Compound J7-2-3 
     6,6-Dimethyl-9-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-2-2 and oxetan-3-one. 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 2.61 min (analysis condition W) 
     Example 421 
     Compound J7-3 
     6,6-Dimethyl-11-oxo-9-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and 4-pyrrolidin-1-yl-piperidine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 13.12 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.01 (1H, s), 7.72 (1H, d, J=8.7 Hz), 7.68 (1H, d, J=2.6 Hz), 7.62 (1H, dd, J=8.2, 1.2 Hz), 7.38 (1H, dd, J=9.1, 2.8 Hz), 3.90 (2H, d, J=11.5 Hz), 2.76 (2H, t, J=12.2 Hz), 2.14 (2H, d, J=10.9 Hz), 1.91 (4H, br), 1.74 (6H, s). 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 1.35 min (analysis condition S) 
     Example 422 
     Compound J7-4 
     9-(4-Isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and 1-isopropyl-piperazine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.80 (1H, s), 8.33 (1H, d, J=7.6 Hz), 8.02 (1H, s), 7.66 (3H, m), 7.33 (1H, d, J=8.2 Hz), 3.21 (4H, br), 2.66 (5H, m), 1.72 (6H, s), 1.02 (6H, d, J=6.3 Hz). 
     LCMS: m/z 413 [M+H] +   
     HPLC retention time: 1.38 min (analysis condition S) 
     Example 423 
     Compound J7-5 
     6,6-Dimethyl-11-oxo-9-pyrrolidin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and pyrrolidine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.24 (1H, d, J=8.1 Hz), 7.91 (1H, s), 7.59 (1H, d, J=8.6 Hz), 7.45 (1H, d, J=7.9 Hz), 7.30 (1H, d, J=2.6 Hz), 6.85 (1H, dd, J=8.6, 2.8 Hz), 3.31 (4H, t, J=6.3 Hz), 1.99 (4H, t, J=6.2 Hz), 1.67 (6H, s). 
     LCMS: m/z 356 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition S) 
     Example 424 
     Compound J7-6 
     6,6-Dimethyl-11-oxo-9-((S)-2-pyrrolidin-1-yl methyl-pyrrolidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and (S)-2-pyrrolidin-1-yl methyl-pyrrolidine. 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 1.50 min (analysis condition S) 
     Example 425 
     Compound J7-7 
     6,6-Dimethyl-11-oxo-9-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and piperazine. 
     LCMS: m/z 371 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 426 
     Compound J7-8 
     9-(3-Hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound J6. 
     LCMS: m/z 369 [M+H] +   
     HPLC retention time: 2.16 min (analysis condition S) 
     Example 427 
     Compound J7-9 
     9-Ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-2, the title compound was prepared from Compound J7-8. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.31 (1H, d, J=8.1 Hz), 8.23 (1H, d, J=1.8 Hz), 8.02 (1H, d, J=1.3 Hz), 7.93 (1H, d, J=8.2 Hz), 7.78 (1H, dd, J=8.2, 1.8 Hz), 7.61 (1H, dd, J=8.1, 1.3 Hz), 4.31 (1H, s), 1.77 (6H, s). 
     LCMS: m/z 311 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition S) 
     Example 428 
     Compound J7-10-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound J6. 
     LCMS: m/z 468 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition S) 
     Example 429 
     Compound J7-10-2 
     6,6-Dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J7-10-1. 
     LCMS: m/z 368 [M+H] +   
     HPLC retention time: 1.27 min (analysis condition S) 
     Example 430 
     Compound J7-11-1 
     9-(Piperidin-4-ylmethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-25-1 and Compound B2-25-2, the title compound was prepared from Compound J6. 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 1.42 min (analysis condition S) 
     Example 431 
     Compound J7-11-2 
     9-(1-Isopropyl-piperidin-4-ylmethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-11-1 and acetone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.79 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.98 (1H, d, 1.8 Hz), 7.79 (1H, d, 7.9 Hz), 7.61 (1H, d, 7.9 Hz), 7.51-7.49 (1H, m), 2.74 (2H, d, 11.0 Hz), 2.64-2.60 (3H, m), 2.04 (2H, t, 10.7 Hz), 1.77 (6H, s), 1.60-1.51 (3H, m), 1.23-1.14 (2H, m), 0.94 (6H, d, 6.7 Hz) 
     LCMS: m/z 426 [M+H] +   
     Example 432 
     Compound J7-12 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid 
     
       
         
         
             
             
         
       
     
     9-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound J5, 30 mg, 0.099 mmol), 4-bromo-butyric acid methyl ester (24.9 μl, 0.198 mmol) and cesium carbonate (64.5 mg, 0.198 mmol) were dissolved in DMA (0.20 ml) and stirred at room temperature for 4 hr. Water was added to the reaction solution, which was then extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The yellow solid obtained after concentration under reduced pressure was purified by silica gel column chromatography (methylene chloride/MeOH) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid methyl ester as an intermediate. 
     The intermediate was dissolved in MeOH (0.50 ml), added with aqueous solution of sodium hydroxide (6 mol/l) and stirred at room temperature for 30 min. The reaction solution was added with hydrochloric acid (3 mol/l), extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, white solid was obtained, which was then washed with methylene chloride to obtain the title compound (19.0 mg, 70%). 
     LCMS: m/z 389 [M+H] +   
     HPLC retention time: 2.39 min (analysis condition F) 
     Example 433 
     Compound J7-13 
     5-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-pentanoic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound J7-12, Compound J5 and 5-bromo-pentanoic acid methyl ester were reacted to obtain the target compound (19.5 mg, 64%). 
     LCMS: m/z 403 [M+H] +   
     HPLC retention time: 2.49 min (analysis condition F) 
     Example 434 
     Compound J7-14 
     6-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-hexanoic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound J7-12, Compound J5 and 6-bromo-hexanoic acid ethyl ester were reacted to obtain the target compound (19.6 mg, 66%). 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 2.61 min (analysis condition F) 
     Example 435 
     Compound J7-15 
     3-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-ethoxy]-propionic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, Compound JJ2 and 3-(2-hydroxy-ethoxy)-propionic acid tert-butyl ester were reacted to obtain 3-[2-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-ethoxy]-propionic acid tert-butyl ester. 
     The resultant was dissolved in DMA (0.30 ml), added with copper cyanide (25.5 mg, 0.285 mmol), and stirred at 200° C. for 1 hr under irradiation with microwave. The reaction solution was diluted with ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. The residues obtained after concentration under reduced pressure were dissolved in methylene chloride (0.75 ml). The solution was added with TFA (250 l) and stirred at room temperature for 5 min. Thereafter, the residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/MeOH) to obtain the title compound (5.6 mg, 14%). 
     LCMS: m/z 419 [M+H] +   
     HPLC retention time: 2.31 min (analysis condition F) 
     Example 436 
     Compound J7-16 
     6,6-Dimethyl-11-oxo-9-(pyridin-4-yl methoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J5 and pyridin-4-yl-methanol (pale yellow solid, 6.1 mg, 31%). 
     LCMS: m/z 394 [M+H] +   
     HPLC retention time: 1.97 min (analysis condition F) 
     Example 437 
     Compound J7-17 
     6,6-Dimethyl-11-oxo-9-(pyridin-3-yl methoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound JJ3-1, the title compound was prepared from Compound J5 and pyridin-3-yl-methanol (pale yellow solid, 7.9 mg, 38%). 
     LCMS: m/z 394 [M+H] +   
     HPLC retention time: 1.99 min (analysis condition F) 
     Example 438 
     Compound J8-1 
     6,6-Dimethyl-9-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-7 and oxetan-3-one. 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 439 
     Compound J8-2 
     9-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-7 and (1-ethoxycyclopropoxy)trimethylsilane. 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 1.39 min (analysis condition S) 
     Example 440 
     Compound J8-3 
     9-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound J7-10-2. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.81 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.26 (1H, d, 2.4 Hz), 8.01 (1H, s), 7.88-7.81 (2H, m), 7.61 (1H, d, 7.9 Hz), 6.36 (1H, s), 3.93 (2H, d, 3.0 Hz), 3.45 (2H, t, 5.8 Hz), 2.97 (3H, s), 2.73-2.70 (2H, m), 1.78 (6H, s) 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 2.15 min (analysis condition S) 
     Example 441 
     Compound J8-4 
     9-(1-Isopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and acetone. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.82 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.22 (1H, d, 1.8 Hz), 8.02 (1H, s), 7.84 (1H, d, 8.5 Hz), 7.78 (1H, dd, 8.2, 2.1 Hz), 7.62 (1H, d, 7.9 Hz), 6.32 (1H, t, 3.7 Hz), 3.23-3.20 (2H, m), 2.83-2.76 (1H, m), 2.72 (2H, t, 5.5 Hz), 2.56-2.54 (2H, m), 1.78 (6H, s), 1.06 (6H, d, 6.7 Hz) 
     LCMS: m/z 410 [M+H] +   
     HPLC retention time: 1.38 min (analysis condition S) 
     Example 442 
     Compound J8-5 
     6,6-Dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and oxetan-3-one. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.81 (1H, br. s), 8.34 (1H, d, J=8.2 Hz), 8.22 (1H, d, J=1.8 Hz), 8.03 (1H, s), 7.76-7.90 (2H, m), 7.64 (1H, dd, J=8.2, 1.8 Hz), 6.25-6.34 (1H, m), 4.60 (2H, dd, J=6.6, 6.0 Hz), 4.52 (2H, dd, J=6.6, 6.0 Hz), 3.57 (1H, t, J=6.0 Hz), 3.03 (2H, m), 2.55 (4H, m), 1.77 (6H, s). 
     LCMS: m/z 424 [M+H] +   
     HPLC retention time: 1.34 min (analysis condition S) 
     Example 443 
     Compound J8-6 
     9-(1-Cyclopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and (1-ethoxycyclopropoxy)trimethylsilane. 
     LCMS: m/z 408 [M+H] +   
     HPLC retention time: 1.36 min (analysis condition S) 
     Example 444 
     Compound J9-1 
     4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J7-10-1. 
     LCMS: m/z 414, 470 [M+H] +   
     HPLC retention time: 2.83 min (analysis condition S) 
     Example 445 
     Compound J9-2 
     6,6-Dimethyl-11-oxo-9-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J9-1. 
     LCMS: m/z 370 [M+H] +   
     HPLC retention time: 1.30 min (analysis condition S) 
     Example 446 
     Compound J9-3 
     9-(1-Isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound J9-2 and 2-bromopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.83 (1H, s), 8.34 (2H, d, J=8.1 Hz), 8.05 (2H, m), 7.82 (1H, d, J=8.1 Hz), 7.61 (2H, m), 3.02 (2H, br), 2.42 (2H, br), 1.76 (6H, s), 1.06 (6H, d, J=6.4 Hz). 
     LCMS: m/z 412 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Example 447 
     Compound J9-4 
     6,6-Dimethyl-9-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J8-5. 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 1.26 min (analysis condition S) 
     Example 448 
     Compound J9-5 
     9-(1-Cyclopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J8-6. 
     LCMS: m/z 410 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 449 
     Compound JJ1 
     3-Bromo-9-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     6-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound J2, 2.15 g, 10.5 mmol) and 3-bromophenylhydrazine hydrochloric acid salt (3.11 g, 1.3 eq.) were dissolved in acetic acid (12 mL), and stirred at 100° C. for 2.5 hr under nitrogen atmosphere. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, and dried over magnesium sulfate. After the filtration, it was concentrated under reduced pressure. The resulting residues were dissolved in THF (30 mL) and water (3 mL), added with DDQ (5.96 g, 2.5 eq.) at 0° C., and then stirred at room temperature overnight. The reaction solution was added with MTBE, washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were washed with MTBE to obtain the title compound (brown solid, 1.80 g, 46%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.4 (1H, s), 8.12 (1H, d, J=8.6 Hz), 7.79 (1H, d, J=8.9 Hz), 7.67-7.68 (2H, m), 7.40 (1H, dd, J=1.7, 8.6 Hz), 7.26 (1H, dd, J=2.6, 8.9 Hz), 3.86 (3H, s), 1.72 (6H, s), 
     LCMS: m/z 370 [M+H] +   
     HPLC retention time: 6.45 min (analysis condition H) 
     Example 450 
     Compound JJ2 
     3-Bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-9-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ1, 1.50 g, 4.05 mmol) and pyridinium chloride (15.2 g, 32.5 eq.) were stirred at 160° C. for 12 hr under nitrogen atmosphere. After cooling, water and ethyl acetate were added and the resulting suspension was filtered. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were washed with MTBE to obtain the title compound (brown solid, 1.47 g, 100%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.4 (1H, s), 9.71 (1H, s), 8.11 (1H, d, J=8.2 Hz), 7.64-7.68 (2H, m), 7.57 (1H, d, J=3.0 Hz), 7.38 (1H, dd, J=1.7, 8.2 Hz), 7.07 (1H, dd, J=3.0, 8.6 Hz), 1.69 (6H, s), 
     LCMS: m/z 356 [M+H] +   
     HPLC retention time: 2.52 min (analysis condition F) 
     Example 451 
     Compound JJ3-1 
     3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 3-bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ2, 356 mg, 1.00 mmol) and triphenylphosphine (317 mg, 1.2 eq.) were added with THF (3 ml), followed by dropwise addition of ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (148 μl, 1.2 eq.) and diisopropyl azodicarboxylic acid (252 μl, 1.3 eq.). The mixture was then stirred at 50° C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to yield the solid, which was then washed with dichloromethane to obtain the title compound (white powder, 241.6 mg, 51%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.4 (1H, s), 8.12 (1H, d, J=8.2 Hz), 7.79 (1H, d, J=8.9 Hz), 7.67-7.69 (2H, m), 7.40 (1H, dd, J=1.8, 8.2 Hz), 7.28 (1H, dd, J=3.0, 8.9 Hz), 4.41-4.48 (1H, m), 4.06-4.17 (2H, m), 3.79-3.85 (1H, m), 1.72 (3H, s), 1.38 (3H, s), 1.33 (3H, s), 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 3.08 min (analysis condition F) 
     Example 452 
     Compound JJ3-2 
     3-Bromo-9-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 18.7 mg, 0.0398 mmol) was dissolved in methanol (1 mL) and THF (0.3 mL), added with 1 N hydrochloric acid (5 drops) and stirred at 50° C. for 1 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were added with dichloromethane, and the solid was separated by filtration to obtain the title compound (yellow powder, 16.8 mg, 98%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.43 (1H, s), 8.12 (1H, d, J=8.6 Hz), 7.78 (1H, d, J=8.9 Hz), 7.67-7.70 (2H, m), 7.40 (2H, dd, J=1.8, 8.6 Hz), 7.27 (2H, dd, J=2.8, 8.9 Hz), 4.43 (2H, brs), 4.12 (1H, dd, J=9.9, 4.3 Hz), 3.96 (1H, dd, J=9.7, 6.1 Hz), 3.85 (1H, dd, J=9.9, 5.6 Hz), 3.48 (2H, d, J=5.6 Hz), 1.72 (6H, s), 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 2.02 min (analysis condition F) 
     Example 453 
     Compound JJ4-1 
     3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     To the mixture of 3-bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 33.2 mg, 0.0706 mmol) and sodium hydride (60% in oil, 6.4 mg, 2.3 eq.), DMA (0.55 mL) and methyl iodide (0.015 mL, 3.4 eq.) were added under nitrogen atmosphere at 0° C., and the mixture was stirred at room temperature overnight. The reaction solution was added with water and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting solid was washed with MTBE to obtain the title compound (white solid, 31.2 mg, 91%). 
     LCMS: m/z 484 [M+H] +   
     HPLC retention time: 3.34 min (analysis condition F) 
     Example 454 
     Compound JJ4-2 
     3-Bromo-9-((R)-2,3-dihydroxy-propoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound JJ3-2, the title compound was prepared from Compound JJ4-1 (yellow solid, 13.3 mg, 83%). 
     LCMS: m/z 444 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition F) 
     Example 455 
     Compound JJ5 
     (3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-acetic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, (3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-acetic acid methyl ester was prepared from Compound JJ2 and hydroxy-acetic acid methyl ester. The resultant was dissolved in MeOH (0.35 ml), added with aqueous solution of sodium hydroxide (6 mol/l), and stirred at room temperature for 10 min. The reaction solution was added with hydrochloric acid (3 mol/l), extracted with diethyl ether and dried over anhydrous magnesium sulfate. After the concentration under reduced pressure, white solid was obtained, which was then washed with methylene chloride to obtain the title compound (11.2 mg, 48%). 
     LCMS: m/z 414 [M+H] +   
     HPLC retention time: 2.50 min (analysis condition F) 
     Example 456 
     Compound JJ6 
     4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid 
     
       
         
         
             
             
         
       
     
     3-Bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ2, 20 mg, 0.056 mmol), 4-bromo-butyric acid methyl ester (7.0 μl, 0.056 mmol) and cesium carbonate (36.6 mg, 0.112 mmol) were dissolved in DMA (0.09 ml), and then stirred at room temperature for 1 hr. Thereafter, 4-bromo-butyric acid methyl ester (7.0 μl, 0.056 mmol) was added thereto and the mixture was stirred at room temperature for 3 hr, followed by further stirring at 45° C. for 30 min. The reaction solution was added with water, extracted with diethyl ether and dried over anhydrous magnesium sulfate. After the concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 4-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid methyl ester. This compound was dissolved in MeOH (0.50 ml), added with aqueous solution of sodium hydroxide (6 mol/l), and then stirred at room temperature for 10 min. The reaction solution was added with hydrochloric acid (3 mol/l), extracted with diethyl ether, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain white solid. This white solid was washed with methylene chloride to obtain the title compound (6.1 mg, 25%). 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition F) 
     Example 457 
     Compound JJ7-1 
     3-Bromo-9-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound (white solid, 111.5 mg, 65%) was prepared from Compound JJ2 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol. 
     LCMS: m/z 614 [M+H] +   
     HPLC retention time: 4.04 min (analysis condition F) 
     Example 458 
     Compound JJ7-2 
     3-Bromo-6,6-dimethyl-9-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-9-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ7-1, 13.7 mg, 0.0223 mmol) was dissolved in THF (0.15 mL) and methanol (0.1 mL), added with 0.5 M sulfuric acid (0.05 mL), and then stirred at 60° C. for 3 hr. After cooling, the reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting solid was washed with dichloromethane to obtain the title compound (white solid, 8.4 mg, 82%). 
     LCMS: m/z 460 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition F) 
     Example 459 
     Compound JJ8-1 
     9-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A5-2, the title compound (11.1 mg, 50%) was prepared from Compound JJ7-1 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol. 
     LCMS: m/z 561 [M+H] +   
     HPLC retention time: 3.84 min (analysis condition F) 
     Example 460 
     Compound JJ8-2 
     6,6-Dimethyl-11-oxo-9-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound JJ7-2, the title compound was prepared from 9-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound JJ8-1) (white solid, 7.8 mg, 97%). 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition F) 
     Example 461 
     Compound JJ9-1 
     9-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 49.5 mg, 0.105 mmol) and copper cyanide (90%, 35.3 mg, 3.4 eq.) were added with DMA (0.5 mL), and the mixture was irradiated with microwave at 200° C. for 1 hr under nitrogen atmosphere. After cooling, the reaction solution was added with water and extracted with ethyl acetate. The insoluble matters were separated off by filtration, and the organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were purified by preparative TLC (methanol/dichloromethane) to obtain the title compound (white solid, 8.5 mg, 22%). 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 2.02 min (analysis condition F) 
     Example 462 
     Compound JJ9-2 
     9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound JJ9-1 (white solid, 24.8 mg, 57%). 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 2.81 min (analysis condition F) 
     Example 463 
     Compound JJ9-3 
     9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound JJ4-1, the title compound was prepared from 9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound JJ9-2) (17.0 mg, 84%). 
     LCMS: m/z 431 [M+H] +   
     HPLC retention time: 3.00 min (analysis condition F) 
     Example 464 
     Compound JJ9-4 
     9-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound JJ3-2, the title compound was prepared from 9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (JJ9-3) (white solid, 12.1 mg, 90%). 
     LCMS: m/z 391 [M+H] +   
     HPLC retention time: 2.13 min (analysis condition F) 
     Example 465 
     Compound JJ10-1 
     9-Benzyloxy-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound JJ2 and benzyl bromide (18.2 mg, 61%). 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition D) 
     Example 466 
     Compound JJ10-2 
     5-Benzyl-9-benzyloxy-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound JJ10-1 (5.3 mg, 21%). 
     LCMS: m/z 536 [M+H] +   
     HPLC retention time: 3.17 min (analysis condition D) 
     Example 467 
     Compound JJ10-3 
     3-Bromo-9-(4-methoxy-benzyloxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared by reacting Compound JJ2 and (4-methoxyphenyl)-methanol (7.5 mg, 28%). 
     LCMS: m/z 476 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition D) 
     Example 468 
     Compound K2 
     2-(3-Bromo-4-methoxy-phenyl)-2-methyl-propionitrile 
     
       
         
         
             
             
         
       
     
     To the THF suspension of potassium tert-butoxide (15.35 g, 3 eq.), (3-bromo-4-methoxyphenyl)acetonitrile (Compound K1, 10 g, 0.044 mmol) was added, and then stirred at 0° C. for 1 hr. Then, iodomethane (8.26 ml, 3 eq.) was added and the mixture was stirred at room temperature for 1 hr. To the reaction solution, saturated aqueous solution of ammonium chloride and water were added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (colorless oily substance, 11.24 g, 100%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 7.69 (1H, d, J=2.5 Hz), 7.50 (1H, dd, J=8.6, 2.5 Hz), 7.16 (1H, d, J=8.6 Hz), 3.86 (3H, s), 1.67 (6H, s). 
     HPLC retention time: 2.30 min (analysis condition S) 
     Example 469 
     Compound K3 
     4-(3-Bromo-4-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     To the THF suspension of zinc (5.72 g, 2 eq.), methanesulfonic acid (25.6 μl, 0.01 eq.) was added, and then stirred at 80° C. for 10 min. Then, the THF solution of 2-(3-bromo-4-methoxy-phenyl)-2-methyl-propionitrile (10 g, 39.35 mmol) was added, followed by addition of bromoethyl acetate (11.07 ml, 1.6 eq.) over 1 hr. The mixture was further stirred for 30 min. To the reaction solution, 4 M hydrochloric acid was added, and stirred at room temperature overnight. After extraction with ethyl acetate, the organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (orange oily substance, 9.74 g, 72%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.46 (1H, d, J=2.5 Hz), 7.16 (1H, dd, J=8.6, 2.5 Hz), 6.89 (1H, d, J=8.6 Hz), 4.17-4.08 (2H, m), 3.90 (3H, s), 3.26 (2H, s), 1.49 (6H, s), 1.23 (3H, t, J=7.2 Hz). 
     LCMS: m/z 343, 345 [M+H] +   
     HPLC retention time: 2.64 min (analysis condition S) 
     Example 470 
     Compound K4 
     4-(3-Bromo-4-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     4-(3-Bromo-4-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester (Compound K3, 10.3 g, 30.01 mmol) was dissolved in DMF (80 mL), added with cesium carbonate (24.4 g, 2.5 eq.) and 4-chloro-3-nitro-benzonitrile (7.12 g, 1.3 eq.), and then stirred at 45° C. for 4 hr. The reaction solution was added to 1 N aqueous solution of hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration, and after concentration under reduced pressure the title compound was obtained as a crude product (yellow oily substance). 
     LCMS: m/z 489, 491 [M+H] +   
     HPLC retention time: 2.85, 3.20 min (analysis condition S) 
     Example 471 
     Compound K5 
     2-[1-(3-Bromo-4-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-1H-indole-3-carboxylic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     4-(3-Bromo-4-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester (Compound K4), which had been obtained from the above, was dissolved in THF (140 mL) and water (70 mL), added with Na 2 S 2 O 4  (26.13 g, 5.0 eq.) and stirred at 50° C. overnight. The reaction solution was added to saturated brine and extracted with ethyl acetate. The organic layer was washed with 1 M aqueous solution of potassium carbonate and saturated brine in order, and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by crystallization in MeCN (80 ml) to obtain the title compound (yellow solid, 8.20 g, 62%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.15 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.94 (1H, s), 7.51 (1H, dd, J=8.5, 1.2 Hz), 7.33 (1H, d, J=2.1 Hz), 7.03 (1H, dd, J=8.7, 2.4 Hz), 6.96 (1H, d, J=8.4 Hz), 3.97 (2H, q, J=7.3 Hz), 3.78 (3H, s), 1.80 (6H, s), 1.09 (3H, t, J=7.2 Hz). 
     LCMS: m/z 441, 443 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition S) 
     Example 472 
     Compound K6 
     8-Bromo-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Phosphorus pentoxide-methanesulfonic acid (12 mL) was added with 2-[1-(3-bromo-4-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-1H-indole-3-carboxylic acid ethyl ester (Compound K5, 1.0 g, 2.27 mmol), and the mixture was stirred at room temperature for 20 min. The reaction solution was diluted with MeCN (20 mL), poured into water (20 mL), and the precipitated solid was filtered to obtain the title compound (yellow solid, 763 mg, 85%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.84 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.03 (1H, s), 7.77 (1H, s), 7.64 (1H, dd, J=8.2, 1.4 Hz), 3.97 (3H, s), 1.75 (6H, s). 
     LCMS: m/z 395, 397 [M+H] +   
     HPLC retention time: 2.58 min (analysis condition S) 
     Example 473 
     Compound K7-1 
     9-Methoxy-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 469 [M+H] +   
     HPLC retention time: 1.37 min (analysis condition S) 
     Example 474 
     Compound K7-2 
     9-Methoxy-6,6-dimethyl-8-(4-morpholin-1-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and 4-piperidin-4-yl-morpholine. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.70 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.63 (1H, s), 7.60 (1H, dd, J=8.2, 1.2 Hz), 7.16 (1H, s), 3.89 (3H, s), 3.64 (2H, brd), 2.72 (2H, brd), 1.91 (2H, brd), 1.73 (6H, s), 1.57 (2H, brd). 
     LCMS: m/z 485 [M+H] +   
     HPLC retention time: 1.33 min (analysis condition S) 
     Example 475 
     Compound K7-3 
     9-Methoxy-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the target compound was prepared from Compound K6 and piperazine. 
     LCMS: m/z 401 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 476 
     Compound K7-4 
     9-Methoxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and morpholine. 
     LCMS: m/z 402 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition S) 
     Example 477 
     Compound K8 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound K7-3 and cyclobutanone. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.70 (1H, br. s), 8.31 (1H, d, J=8.2 Hz), 8.00 (1H, s), 7.64 (1H, s), 7.61 (1H, dd, J=8.1, 1.3 Hz), 7.16 (1H, s), 3.88 (3H, s), 3.60 (1H, t, J=6.2 Hz), 3.10-3.25 (4H, m), 2.77 (1H, t, J=7.1 Hz), 2.35-2.51 (4H, m), 1.74 (6H, s), 1.58-2.08 (6H, m). 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.45 min (analysis condition S) 
     Example 478 
     Compound K9-1 
     9-Hydroxy-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound K7-1. 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.22 min (analysis condition S) 
     Example 479 
     Compound K9-2 
     9-Hydroxy-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K7-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.65 (1H, s), 9.61 (1H, s), 8.30 (1H, d, J=8.2 Hz), 7.98 (1H, s), 7.59-7.56 (2H, m), 7.10 (1H, s), 3.71 (2H, brd, J=11.2 Hz), 3.60 (4H, m), 2.66 (2H, m), 1.88 (2H, brd, J=9.7 Hz), 1.71 (6H, s), 1.57 (2H, brd). 
     LCMS: m/z 471 [M+H] +   
     HPLC retention time: 1.20 min (analysis condition S) 
     Example 480 
     Compound K9-3 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K8. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.66 (1H, br. s), 9.67 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.98 (1H, s), 7.56-7.60 (2H, m), 7.09 (1H, s), 3.10-3.24 (4H, m), 2.77 (1H, t, J=7.5 Hz), 2.37-2.49 (4H, m), 1.52-2.07 (6H, m), 1.72 (6H, s). 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 1.31 min (analysis condition S) 
     Example 481 
     Compound K9-4 
     9-Hydroxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K7-4. 
     LCMS: m/z 388 [M+H] +   
     HPLC retention time: 1.67 min (analysis condition S) 
     Example 482 
     Compound K10-1 
     9-Isopropoxy-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-2 and 2-bromopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.68 (1H, s), 8.30 (1H, d, J=8.1 Hz), 7.99 (1H, s), 7.60 (2H, m), 7.14 (1H, s), 4.72-4.63 (2H, m), 3.71 (2H, brd, J=10.7 Hz), 3.59 (6H, m), 2.68 (2H, t, J=12.9 Hz), 2.27 (2H, brd), 1.90 (2H, brd), 1.73 (6H, s), 1.56 (2H, br), 1.34 (6H, d, J=5.9 Hz). 
     LCMS: m/z 513 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition S) 
     Example 483 
     Compound K10-2 
     8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-3 and 2-iodopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.29 (1H, d, J=8.1 Hz), 7.98 (1H, s), 7.56-7.63 (2H, m), 7.14 (1H, s), 4.62-4.74 (1H, m), 3.10-3.26 (4H, m), 2.69-2.85 (1H, m), 2.35-2.48 (4H, m), 1.57-2.08 (6H, m), 1.73 (6H, s), 1.32 (6H, d, J=6.1 Hz). 
     LCMS: m/z 483 [M+H] +   
     HPLC retention time: 1.65 min (analysis condition S) 
     Example 484 
     Compound K10-3 
     9-(2-Methoxy-ethoxy)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 1-bromo-2-methoxyethane. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.67 (1H, s), 8.30 (1H, d, 7.9 Hz), 7.98 (1H, s), 7.64 (1, s), 7.58 (1H, d, 7.9 Hz), 7.16 (1H, s), 4.18-4.22 (2H, m), 3.72-3.80 (6H, m), 3.35 (3H, s), 3.18-3.24 (4H, s), 1.74 (1H, s) 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 3.23 min (analysis condition W) 
     Example 485 
     Compound K10-4 
     9-[2-(2-Methoxy-ethoxy)-ethoxy]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 1-bromo-2-(2-methoxyethoxy)ethane. 
     LCMS: m/z 490 [M+H] +   
     HPLC retention time: 3.16 min (analysis condition W) 
     Example 486 
     Compound K10-5 
     6,6-Dimethyl-8-morpholin-1-yl-11-oxo-9-[(S)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 3-mesyloxytetrahydrofurane. 
     LCMS: m/z 458 [M+H] +   
     HPLC retention time: 3.20 min (analysis condition W) 
     Example 487 
     Compound K10-6 
     9-Isopropoxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 2-bromopropane. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.70 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.63 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.16 (1H, s), 4.75-4.66 (1H, m), 3.77 (4H, m) 3.19 (4H, m), 1.74 (6H, s), 1.35 (3H, s), 1.33 (3H, s) 
     LCMS: m/z 430 [M+H] +   
     Example 488 
     Compound K10-7 
     9-(2-Hydroxy-ethoxy)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 2-bromoethanol. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.71 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.63 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.16 (1H, s), 4.13-4.09 (2H, t, 4.61 Hz), 3.81-3.78 (2H, t, 4.61 Hz), 3.78 (4H, m) 3.23 (4H, m), 1.75 (6H, s) 
     LCMS: m/z 432 [M+H] +   
     Example 489 
     Compound L2-1 
     (4-Isopropoxy-3-methoxy-phenyl)-ethyl acetate ester 
     
       
         
         
             
             
         
       
     
     (4-Hydroxy-3-methoxy-phenyl)-ethyl acetate ester (Compound L1-1, 3.0 g, 14.27 mmol) was dissolved in DMF (70 mL), added with 2-iodopropane (2.9 mL, 2.0 eq.) and potassium carbonate (3.94 g, 2.0 eq.), and stirred at 80° C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 2.61 g, 73%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 6.88 (2H, m), 6.74 (1H, dd, J=8.1, 2.1 Hz), 4.52-4.43 (1H, m), 4.07 (2H, q, J=7.1 Hz), 3.72 (3H, s), 3.56 (2H, s), 1.23 (6H, d, J=6.1 Hz), 1.18 (3H, t, J=7.1 Hz). 
     LCMS: m/z 253 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition S) 
     Example 490 
     Compound L2-2 
     (4-Isopropoxy-3-methoxy-phenyl)-acetic acid isopropyl ester 
     
       
         
         
             
             
         
       
     
     (4-Hydroxy-3-methoxy-phenyl)-acetic acid (Compound L1-2, 1.5 g, 8.23 mmol) was dissolved in DMF (30 mL), added with 2-iodopropane (3.3 mL, 4.0 eq.) and potassium carbonate (4.55 g, 4.0 eq.), and stirred at 80° C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 1.21 g, 55%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 6.87 (2H, s+d), 6.73 (1H, dd, J=8.1, 2.1 Hz), 4.94-4.84 (1H, m), 4.52-4.43 (1H, m), 3.72 (3H, s), 3.52 (2H, s), 1.23 (6H, d, J=6.1 Hz), 1.18 (6H, d, J=6.1 Hz). 
     LCMS: m/z 267 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition S) 
     Example 491 
     Compound L3-1 
     2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K2, the title compound was prepared from Compound L2-1. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 6.90-6.76 (3H, m), 4.53-4.44 (1H, m), 4.06 (2H, q, J=7.1 Hz), 3.73 (3H, s), 1.47 (6H, s), 1.23 (6H, d, J=6.1 Hz), 1.12 (3H, t, J=7.0 Hz). 
     LCMS: m/z 281 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition S) 
     Example 492 
     Compound L3-2 
     2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid isopropyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K2, the title compound was prepared from Compound L2-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 6.88 (1H, d, J=8.2 Hz), 6.79 (2H, m), 4.94-4.84 (1H, m), 4.53-4.44 (1H, m), 3.72 (3H, s), 1.45 (6H, s), 1.23 (6H, d, J=6.1 Hz), 1.12 (6H, d, J=6.3 Hz). 
     LCMS: m/z 295 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition S) 
     Example 493 
     Compound L4 
     2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid 
     
       
         
         
             
             
         
       
     
     2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid ethyl ester (Compound L3-1, 1.45 g, 5.17 mmol) was dissolved in THF (13 mL) and EtOH (13 mL), added with 1 N aqueous solution of sodium hydroxide (10.3 mL, 2.0 eq.), and stirred at 80° C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The aqueous layer was acidified by using 1 N aqueous solution of hydrochloric acid, extracted with ethyl acetate, washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white solid, 1.10 g, 84%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.26 (1H, s), 6.90-6.80 (3H, m), 4.49 (1H, m), 3.73 (3H, s), 1.45 (6H, s), 1.23 (6H, d, J=6.1 Hz). 
     LCMS: m/z 253 [M+H] +   
     HPLC retention time: 1.83 min (analysis condition S) 
     Example 494 
     Compound L5 
     4-(4-Isopropoxy-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid (Compound L4, 1.4 g, 5.55 mmol) was added with thionyl chloride (10 mL), and then stirred at room temperature for 5 hr. According to the concentration under reduced pressure, unreacted thionyl chloride was removed to obtain corresponding acid chloride. 
     To MeCN (40 mL), malonic acid monoethyl ester potassium salt (1.98 g, 2.1 eq.), triethylamine (2.47 mL, 3.2 eq.), and magnesium chloride (1.32 g, 2.5 eq.) were added and the mixture was stirred at room temperature for 2 hr. To the reaction solution, MeCN (15 mL) solution of the acid chloride prepared from the above was added dropwise. Upon the completion of the dropwise addition, the mixture was further stirred at room temperature for overnight. MeCN was removed by distillation and concentrated under reduced pressure, and the resulting residues were added with 1 N aqueous solution of hydrochloric acid, extracted with toluene, washed with saturated brine, and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 1.45 g, 81%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 6.94 (1H, d, J=8.2 Hz), 6.76 (2H, m), 4.56-4.47 (1H, m), 4.00 (2H, q, J=7.1 Hz), 3.74 (3H, s), 3.38 (2H, s), 1.41 (6H, s), 1.24 (6H, d, J=6.1 Hz), 1.12 (3H, t, J=7.3 Hz). 
     LCMS: m/z 323 [M+H] +   
     HPLC retention time: 2.45, 3.03 min (analysis condition S) 
     Example 495 
     Compound L6 
     2-(4-Cyano-2-nitro-phenyl)-4-(4-isopropoxy-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K4, the title compound was prepared from Compound L5. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 8.35 (1H, d, J=1.8 Hz), 8.14 (1H, dd, J=8.2, 1.9 Hz), 7.67 (1H, d, J=8.2 Hz), 6.68 (1H, d, J=8.4 Hz), 6.59 (1H, dd, J=8.4, 2.0 Hz), 6.45 (1H, d, J=2.1 Hz), 5.44 (1H, s), 4.43 (1H, m), 4.09 (2H, q, J=7.1 Hz), 3.53 (3H, s), 1.59 (3H, s), 1.35 (3H, s), 1.24 (6H, d×2), 1.13 (3H, t, J=7.1 Hz). 
     LCMS: m/z 469 [M+H] +   
     HPLC retention time: 2.85, 3.10 min (analysis condition S) 
     Example 496 
     Compound L7 
     6-Cyano-2-[1-(4-isopropoxy-3-methoxy-phenyl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound K5, the title compound was prepared from Compound L6. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.04 (1H, s), 8.05 (1H, d, J=8.4 Hz), 7.93 (1H, s), 7.49 (1H, dd, J=8.4, 1.5 Hz), 6.79 (2H, m), 6.54 (1H, dd, J=8.3, 1.9 Hz), 4.43 (1H, t, J=6.1 Hz), 3.94 (2H, q, J=7.0 Hz), 3.65 (3H, s), 1.81 (6H, s), 1.21 (6H, d, J=5.9 Hz), 1.05 (3H, t, J=7.1 Hz). 
     LCMS: m/z 421 [M+H] +   
     HPLC retention time: 2.82 min (analysis condition S) 
     Example 497 
     Compound L8-1 
     9-Hydroxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-[1-(4-isopropoxy-3-methoxy-phenyl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (Compound L7, 1.25 g, 2.97 mmol) was dissolved in MeCN (18 mL), added with methanesulfonic acid (3.75 mL), and then stirred at 50° C. for 8 hr. Hexane was added to the reaction solution, and the precipitated solid was filtered to obtain the title compound (yellow solid, 185 mg, 19%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.67 (1H, s), 8.30 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.59 (2H, m), 7.28 (1H, s), 3.93 (3H, s), 1.75 (6H, s). 
     LCMS: m/z 333 [M+H] +   
     HPLC retention time: 1.73 min (analysis condition S) 
     Example 498 
     Compound L8-2 
     9-Isopropoxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the filtrate obtained from the synthesis of Compound L8-1, water was added and the extraction was carried out with ethyl acetate. The resultant was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the concentration was performed under reduced pressure to obtain the target compound (red amorphous, 830 mg, 75%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.72 (1H, s), 8.31 (1H, d, J=8.4 Hz), 8.01 (1H, d, J=0.7 Hz), 7.66 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.33 (1H, s), 4.65 (1H, m), 3.93 (3H, s), 1.77 (6H, s), 1.32 (6H, d, J=6.1 Hz). 
     LCMS: m/z 375 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition S) 
     Example 499 
     Compound L9 
     8-Hydroxy-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound L8-2. 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 12.69 (1H, s), 9.69 (1H, s), 8.30 (1H, d, J=8.1 Hz), 7.99 (1H, s), 7.65 (1H, s), 7.60 (1H, dd, J=8.2, 1.2 Hz), 7.17 (1H, s), 4.64 (1H, m), 1.69 (6H, s), 1.32 (6H, d, J=6.1 Hz). 
     LCMS: m/z 361 [M+H] +   
     HPLC retention time: 2.20 min (analysis condition S) 
     Example 500 
     Compound L10-1 
     8-(1-Cyclobutyl-piperidin-4-yloxy)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound L9 and 1-cyclobutylpiperidin-4-ol. 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 9.31 (1H, br. s), 8.54-8.50 (1H, d, 8.08 Hz), 7.90 (1H, s), 7.77 (1H, s), 7.59-7.55 (1H, m), 7.09 (1H, s), 4.70-4.61 (1H, m), 4.52-4.43 (1H, m), 2.79-2.73 (1H, m), 2.70-2.60 (2H, m), 2.25-2.16 (2H, m), 2.09-1.99 (4H, m), 1.98-1.88 (4H, m), 1.77 (6H, s), 1.72-1.58 (2H, m), 1.39 (3H, s), 1.37 (3H, s) 
     LCMS: m/z 498 [M+H] +   
     Example 501 
     Compound L10-2 
     8-((R)-1-Cyclobutyl-pyrrolidin-3-yl oxy)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound L9 and (S)-1-cyclobutylpyrrolidin-3-ol. 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 10.63 (1H, br. s), 8.51-8.48 (1H, d, 8.08 Hz), 7.89 (1H, s), 7.85 (1H, s), 7.55-7.51 (1H, m), 6.99 (1H, s), 5.03-4.97 (1H, m), 4.71-4.62 (1H, m), 3.07-292 (2H, m), 2.84-2.73 (2H, m), 2.64-2.53 (1H, m), 2.36-2.23 (2H, m), 2.10-1.97 (2H, m), 1.83-1.67 (2H, m), 1.78 (6H, s), 1.53-1.46 (2H, m), 1.39 (3H, s), 1.37 (3H, s) 
     LCMS: m/z 484 [M+H] +   
     Example 502 
     Compound M1 
     7-Methoxy-3,4-dihydro-2H-spiro[cyclopentane-1,1′-naphthalen]-2-one 
     
       
         
         
             
             
         
       
     
     To the THF (300 ml) solution of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 0.5 g, 2.84 mmol), sodium hydride (36.4 mg, 2.2 eq.) was added at 0° C. After stirring for 20 min, 1,4-dibromobutane (0.74 ml, 1.2 eq.) was added dropwise thereto, and the mixture was stirred at 80° C. for 4 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous solution of ammonium chloride and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow solid, 0.31 g, 47%). 
       1 H-NMR (CDCl 3 , 300 MHz) δ: 1.79-1.92 (6H, m), 2.42-2.27 (m, 2H), 3.03 (t, 2H, J=6.5 Hz), 3.81 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 6.73 (dd, 1H, J=2.7 Hz, 8.0 Hz), 6.83 (d, 1H, J=2.7 Hz), 7.09 (d, 1H, J=8.0 Hz) 
     LCMS: m/z 231 [M+H] +   
     Example 503 
     Compound M2 
     3-Bromo-8-methoxy-5,11-dihydrospiro[benzo[b]carbazole-6,1′-cyclopentane] 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound M1 and (3-bromo-phenyl)-hydrazine. 
     LCMS: m/z 380, 382 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition Y) 
     Example 504 
     Compound M3 
     3-Bromo-8-methoxyspiro[benzo[b]carbazole-6,1′-cyclopentan]-11(5H)-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound M2. 
       1 H-NMR (CDCl 3 , 300 MHz) δ: 2.11-2.51 (8H, m), 3.91 (s, 3H), 6.98 (dd, 1H, J=2.3 Hz, 8.8 Hz), 7.01 (d, 1H, J=2.3 Hz), 7.41 (dd, 1H, J=1.5 Hz, 8.4 Hz), 7.57 (d, 1H, J=1.5 Hz), 8.30 (d, 1H, J=8.4 Hz), 8.35 (d, 1H, J=8.8 Hz), 8.69 (s, 1H) 
     LCMS: m/z 396, 398 [M+H] +   
     Example 505 
     Compound M4 
     8-Methoxy-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1′-cyclopentane]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound M3. 
       1 H-NMR (DMSO-d 6 , 300 MHz) δ: 2.14-2.37 (m, 8H), 3.90 (s, 3H), 7.05-7.10 (m, 2H), 7.60 (dd, 1H, J=1.5 Hz, 8.4 Hz), 7.95 (s, 1H), 8.13 (d, 1H, J=9.5 Hz), 8.30 (d, 1H, J=8.4 Hz), 12.24 (s, 1H) 
     LCMS: m/z 343 [M+H] +   
     Example 506 
     Compound M5 
     8-Hydroxy-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1′-cyclopentane]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound M4. 
       1 H-NMR (DMSO-d 6 , 300 MHz) δ: 2.06-2.39 (m, 8H), 6.87 (dd, 1H, J=1.9 Hz, 8.8 Hz), 6.90 (d, 1H, J=1.9 Hz), 7.57 (dd, 1H, J=1.1 Hz, 8.0 Hz), 7.95 (s, 1H), 8.02 (d, 1H, J=8.8 Hz), 8.30 (d, 1H, J=8.0 Hz), 10.29 (s, 1H), 12.25 (s, 1H) 
     LCMS: m/z 329 [M+H] +   
     Example 507 
     Compound M6-1 
     (S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1′-cyclopentane]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared as a crude product from Compound M5 and toluene-4-sulfonic acid(R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester. 
     Example 508 
     Compound M6-2 
     (R)-8-(2,3-Dihydroxypropoxy)-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1′-cyclopentane]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound M6-1. 
     LCMS: m/z 403 [M+H] +   
     HPLC retention time: 2.88 min (analysis condition U) 
     Example 509 
     Compound N1 
     7-Methoxy-2′,3,3′,4,5′,6′-hexahydro-2H-spiro[naphthalene-1,4′-pyran]-2-one 
     
       
         
         
             
             
         
       
     
     To the THF (300 ml) solution of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 20 g, 0.11 mol), sodium hydride (9.9 g, 3.7 eq.) was added at 0° C. After stirring for 10 min, 1-bromo-2-(2-bromo-ethoxy)-ethane (19 ml, 12 eq.) was added dropwise thereto, and the mixture was stirred at 80° C. for 3 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added and the extraction was carried out twice with ethyl acetate. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white solid, 13 g, 51%). 
       1 H-NMR (300 MHz, CDCl 3 ) δ: 2.07 (4H, m), 2.70 (t, 2H, 6.8 Hz), 3.12 (t, 2H, 6.8 Hz), 3.81 (s, 3H), 3.89 (m, 4H), 6.75 (dd, 1H, 2.6 Hz, 8.3 Hz), 6.9 (d, 1H, 2.6 Hz), 7.0 (d, 1H, 8.3 Hz) 
     LCMS: m/z 247 [M+H] +   
     Example 510 
     Compound N2-1, Compound N2-2 
     3-Bromo-8-methoxy-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran] 
     1-Bromo-8-methoxy-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran] 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared as a mixture from Compound N1. 
     Example 511 
     Compound N3 
     3-Bromo-8-methoxy-2′,3′,5′,6′-tetrahydrospiro[benzo[b]carbazole-6,4′-pyran]-11(5H)-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound N2-1. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.9 (2H, m), 2.4 (m, 2H), 3.9 (s, 3H), 4.0 (m, 2H), 4.2 (m, 2H), 7.1 (dd, 1H, 2.2 Hz, 8.7 Hz), 7.3 (m, 2H), 7.8 (d, 1H, 2.2 Hz), 8.1 (d, 2H, 8.7 Hz), 11.8 (s, 1H) 
     LCMS: m/z 413 (M+1) +   
     Example 512 
     Compound N4 
     8-Methoxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound N3. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.9 (m, 2H), 2.4 (m, 2H), 3.9 (s, 3H), 4.0 (m, 2H), 4.1 (m, 2H), 7.1 (dd, 1H, 2.2 Hz, 8.7 Hz), 7.4 (d, 1H, 2.2 Hz), 7.6 (dd, 1H, 1.5 Hz, 8.3 Hz), 8.0 (s, 1H), 8.1 (d, 1H, 8.7 Hz), 8.3 (d, 1H, 8.3 Hz), 12.2 (s, 1H) 
     LCMS: m/z 359 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition U) 
     Example 513 
     Compound N5 
     8-Hydroxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound N4. 
       1 H-NMR (300 MHz, DMSO-d 6 ) d ppm 2.0 (m, 2H), 2.3 (m, 2H), 4.0 (m, 2H), 4.1 (m, 2H), 6.9 (dd, 1H, 1.9 Hz, 8.3 Hz), 7.3 (d, 1H, 1.9 Hz), 7.6 (dd, 1H, 1.5 Hz, 8.3 Hz), 8.0 (s, 1H), 8.1 (d, 1H, 8.3 Hz), 8.3 (d, 1H, 8.3 Hz), 10.3 (s, 1H), 12.2 (s, 1H) 
     LCMS: m/z 345 [M+H] +   
     HPLC retention time: 2.37 min (analysis condition U) 
     Example 514 
     Compound N6-1-1 
     (S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl) methoxy)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound N6-2 and (S)-2,2-dimethyl-4-p-tolyloxymethyl-[1,3]dioxolane. 
     LCMS: m/z 459 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition Y) 
     Example 515 
     Compound N6-1-2 
     (R)-8-(2,3-Dihydroxypropoxy)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound N6-1-1. 
     LCMS: m/z 419 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition S) 
     Example 516 
     Compound N6-2 
     11-Oxo-8-(piperidin-4-yloxy)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1 and Compound A8-1, the title compound was prepared from Compound N5. 
     LCMS: m/z 428 [M+H] +   
     HPLC retention time: 1.38 min (analysis condition S) 
     Example 517 
     Compound N6-3 
     8-(3-Morpholinoethoxy)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5. 
     LCMS: m/z 458 [M+H] +   
     HPLC retention time: 1.33 min (analysis condition S) 
     Example 518 
     Compound N6-4 
     8-(3-Morpholinopropoxy)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5. 
     LCMS: m/z 472 [M+H] +   
     HPLC retention time: 1.41 min (analysis condition S) 
     Example 519 
     Compound N6-5 
     3-Cyano-8-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5. 
     LCMS: m/z 506 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition S) 
     Example 520 
     Compound N6-6 
     8-(1-Ethylpiperidin-4-yloxy)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound N6-2. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.02 (3H, t, 7.25 Hz), 1.18 (2H, m), 1.71 (2H, m), 1.97 (4H, m), 2.27 (2H, m), 2.38 (3H, m), 2.71 (2H, m), 4.03 (2H, m), 4.21 (2H, m), 4.66 (1H, s), 7.13 (1H, dd, 8.77 Hz, 1.91 Hz), 7.39 (1H, bs, 1.91 Hz), 7.60 (1H, d, 8.40 Hz), 8.07 (1H, s), 8.15 (1H, d, 8.40 Hz), 8.37 (1H, d, 8.01 Hz), 12.2 (1H, s). 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition S) 
     Example 521 
     Compound N7 
     Trifluoromethanesulfonic acid 3-cyano-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound N5. 
     LCMS: m/z 477 [M+H] +   
     HPLC retention time: 3.58 min (analysis condition Y) 
     Example 522 
     Compound N8-1 
     11-Oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound N7 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 481 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition U) 
     Example 523 
     Compound N8-2 
     8-(4-Morpholinopiperidin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound N7 and 4-piperidin-4-yl-morpholine. 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 1.70 min (analysis condition U) 
     Example 524 
     Compound O1 
     6-Bromo-7-methoxy-2′,3,3′,4,5′,6′-hexahydro-2H-spiro[naphthalene-1,4′-pyran]-2-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E-1, the title compound was prepared from Compound N1. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 2.01 (4H, m), 2.66 (2H, t, 6.87 Hz), 3.08 (2H, t, 6.87 Hz), 3.62 (2H, m), 3.78 (2H, m), 3.87 (3H, s), 7.00 (1H, s), 7.43 (1H, s) 
     Example 525 
     Compound O2 
     9-Bromo-8-methoxy-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared as a crude product from Compound O1. 
     Example 526 
     Compound O3 
     9-Bromo-8-methoxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound O2. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.95 (2H, d, 14.87 Hz), 2.55 (2H, m), 4.04 (2H, m), 4.09 (3H, s), 4.22 (2H, m), 7.51 (1H, s), 7.63 (1H, dd, 8.01 Hz, 1.53 Hz), 8.09 (1H, s), 8.30 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s). 
     LCMS: m/z 437, 439 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition U) 
     Example 527 
     Compound O4 
     9-Fluoro-8-methoxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound O5-3, the title compound was prepared from Compound O3. 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 2.29 min (analysis condition S) 
     Example 528 
     Compound O5-1 
     9-Fluoro-8-hydroxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound O4. 
     LCMS: m/z 363 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition S) 
     Example 529 
     Compound O5-2 
     Trifluoromethanesulfonic acid 3-cyano-9-fluoro-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound O5-1. 
     LCMS: m/z 495 [M+H] +   
     HPLC retention time: 3.47 min (analysis condition Y) 
     Example 530 
     Compound O5-3 
     9-Fluoro-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the THF (0.9 ml) solution of 9-bromo-6-tetrahydropyran-8-pyrrolidinopiperidin-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound O8-1, 90 mg, 0.161 mmol), THF solution of n-butyl lithium (2 M solution, 0.241 ml, 3 eq.) was added at −78° C. After stirring for 30 min, THF (1 ml) solution of N-fluorobenzenesulfonimide (152 mg, 3 eq.) was added dropwise thereto. After rising to room temperature, the mixture was stirred for 18 hr. To the reaction solution, water was added and the extraction was carried out with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance chromatography to obtain the target compound (white solid, 0.44 mg, 0.5%). 
       1 H-NMR (CDCl 3 +CD 3 OD, 300 MHz) δ: 1.75-1.94 (m, 11H), 2.02-2.01 (m, 2H), 2.30-2.27 (m, 1H), 2.75-2.72 (m, 2H), 2.90-3.00 (m, 2H), 3.61-3.47 (m, 4H), 4.01-3.90 (m, 4H), 7.08 (dd, 1H, J=1, 2 Hz, 8.4 Hz), 7.29 (dd, 1H, J=1, 5 Hz, 8.1 Hz), 7.68 (d, 1H, J=12.9 Hz), 7.72 (s, 1H), 8.22 (d, 1H, J=8.4 Hz) 
     LCMS: m/z 499 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition U) 
     Example 531 
     Compound O5-4 
     8-(4-Cyclobutylpiperazin-1-yl)-9-fluoro-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O5-2 and 1-cyclobutylpiperazine. 
     LCMS: m/z 485 [M+H] +   
     HPLC retention time: 1.97 min (analysis condition U) 
     Example 532 
     Compound O6-1 
     9-Bromo-8-hydroxy-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound O3. 
     LCMS: m/z 423, 425 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition U) 
     Example 533 
     Compound O6-2 
     Trifluoromethanesulfonic acid 9-bromo-3-cyano-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound O6-1. 
     LCMS: m/z 555, 557 [M+H] +   
     HPLC retention time: 3.13 min (analysis condition U) 
     Example 534 
     Compound O7-1 
     9-Bromo-11-oxo-8-(piperazin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and piperazine. 
     LCMS: m/z 491, 493 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 535 
     Compound O7-2 
     4-(9-Bromo-3-cyano-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl)piperazine-1-carboxylic acid tert-butyl 
     
       
         
         
             
             
         
       
     
     To the dichloromethane (5 mL) solution of 9-bromo-11-oxo-8-(piperazin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile (Compound O7-1, 250 mg, 0.509 mmol) and mono-tert-butyl ester carbonic anhydride (122 mg, 0.560 mmol), triethylamine (0.21 mL, 1.53 mmol) was added at 0° C., and stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound as a white solid (212 mg, 70%). 
       1 H-NMR (300 MHz, DMSO-d 6 ) d ppm: 1.44 (9H, s), 1.97 (2H, m), 2.44 (2H, m), 1.35 (4H, m), 3.54 (4H, m), 4.06 (2H, m), 4.18 (2H, m), 7.57 (1H, s), 7.63 (1H, dd, 8.01 Hz, 1.52 Hz), 8.08 (1H, d, 1.52 Hz), 8.31 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s) 
     LCMS: m/z 591, 593 [M+H] +   
     HPLC retention time: 3.23 min (analysis condition T) 
     Example 536 
     Compound O7-3 
     Tert-butyl 4-(3-cyano-11-oxo-9-(prop-1-ynyl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl)piperazine-1-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O7-2. 
     LCMS: m/z 551 [M+H] +   
     HPLC retention time: 3.92 min (analysis condition Y) 
     Example 537 
     Compound O7-4 
     11-Oxo-8-(piperazin-1-yl)-9-(prop-1-ynyl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound O7-3. 
     LCMS: 451 m/z [M+H] +   
     HPLC retention time: 1.87 min (analysis condition U) 
     Example 538 
     Compound O7-5 
     4-(3-Cyano-9-ethynyl-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl)piperazine-1-carboxylic acid tert-butyl 
     
       
         
         
             
             
         
       
     
     LCMS: m/z 537 [M+H] +   
     HPLC retention time: 3.82 min (analysis condition Y) 
     Example 539 
     Compound O8-1 
     9-Bromo-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 559, 561 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition U) 
     Example 540 
     Compound O8-2 
     9-Bromo-8-(4-cyclobutylpiperazin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 1-cyclobutylpiperazine. 
     LCMS: m/z 547 [M+H] +   
     HPLC retention time: 1.61 min (analysis condition S) 
     Example 541 
     Compound O8-3 
     9-Bromo-8-(4-morpholinopiperidin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 4-piperidin-4-yl-morpholine. 
     LCMS: m/z 575, 577 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition U) 
     Example 542 
     Compound O8-4 
     9-Bromo-8-(4-(oxetan-3-yl)piperazin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O7-1 and oxetan-3-one. 
     LCMS: m/z 547, 549 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 543 
     Compound O8-5 
     9-Bromo-8-(4-tert-butylpiperazin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 1-tert-butylpiperazine. 
     LCMS: 547, 549 m/z [M+H] +   
     HPLC retention time: 2.07 min (analysis condition U) 
     Example 544 
     Compound O9-1 
     11-Oxo-9-(prop-1-ynyl)-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Bromo-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile (Compound O8-1, 100 mg, 0.170 mmol), tin tributyl(1-propynyl) (0.082 mL, 0.268 mmol), bis(acetonitrile) palladium dichloride (II) (2.64 mg, 0.00895 mmol), X-Phos (12.8 mg, 0.0269 mmol), and cesium carbonate (262.4 mg, 0.806 mmol) were suspended in acetonitrile (1 mL), and then stirred at 80° C. for 2 hr. The reaction mixture was cooled to room temperature followed by addition of water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (pale yellow solid, 3.8 mg, 4.1%). 
       1 H-NMR (300 MHz, DMSO) σppm 12.20 (bs, 1H), 8.35 (d, 1H, J=8.1 Hz), 8.06 (s, 1H), 8.06 (d, 1H, J=10.8 Hz), 7.58 (d, 1H, J=8.4 Hz), 7.29 (s, 1H), 4.25-4.23 (m, 2H), 4.02-3.98 (m, 2H), 3.78 (d, 2H, J=11.4 Hz), 2.93 (t, 2H, J=11.1 Hz), 2.55 (s, 1H), 2.45-2.28 (m, 2H), 2.24-2.05 (m, 4H), 2.08-1.81 (m, 4H), 1.75-1.50 (m, 7H) 
     LCMS: m/z 519 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition U) 
     Example 545 
     Compound O9-2 
     9-Ethynyl-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound O8-1. 
     LCMS: m/z 505 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition U) 
     Example 546 
     Compound O9-3 
     11-Oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3,9-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound O8-1. 
     LCMS: 506 m/z [M+H] +   
     HPLC retention time: 1.87 min (analysis condition U) 
     Example 547 
     Compound O9-4 
     9-(3-Hydroxy-3-methylbut-1-ynyl)-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound O8-1. 
     LCMS: m/z 563 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition U) 
     Example 548 
     Compound O9-5 
     8-(4-Cyclobutylpiperazin-1-yl)-11-oxo-9-(prop-1-ynyl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O8-2. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.6 (m, 2H), 1.8 (m, 2H), 1.9 (m, 4H), 2.1 (s, 3H), 2.4 (m, 6H), 2.8 (m, 1H), 3.4 (m, 4H), 4.0 (m, 2H), 4.1 (m, 2H), 7.3 (s, 1H), 7.6 (d, 1H, 8.0 Hz), 8.0 (m, 2H), 8.3 (d, 1H, 8.0 Hz), 12.2 (s, 1H) 
     LCMS: m/z 505 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition U) 
     Example 549 
     Compound O9-6 
     8-(4-Cyclobutylpiperazin-1-yl)-9-ethynyl-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound O8-2. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.66 (2H, m), 1.83 (2H, t, 8.77 Hz), 1.99 (4H, m), 2.41 (6H, m), 2.79 (1H, t, 7.63 Hz), 3.35 (4H, m), 4.01 (2H, m), 4.27 (2H, m), 4.51 (1H, s), 7.33 (1H, s), 7.54 (1H, m), 8.03 (1H, s), 8.16 (1H, s), 8.32 (1H, d, 8.40 Hz), 12.3 (1H, s). 
     LCMS: m/z 491 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition U) 
     Example 550 
     Compound O9-7 
     8-(4-Morpholinopiperidin-1-yl)-11-oxo-9-(prop-1-ynyl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O8-3. 
       1 H-NMR (300 MHz, DMSO-d 6 ) δ: 1.57 (2H, m), 1.95 (4H, m), 2.14 (3H, s), 2.37 (3H, m), 3.35 (4H, m), 2.83 (2H, t, 12.6 Hz), 3.56 (4H, s), 3.86 (2H, d, 11.8 Hz), 4.04 (2H, m), 4.17 (2H, m), 7.31 (1H, s), 7.61 (1H, d, 8.01 Hz), 8.06 (1H, s), 8.07 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s). 
     LCMS: m/z 535 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition U) 
     Example 551 
     Compound O9-8 
     9-Ethynyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from compound 08-3. 
     LCMS: m/z 521 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition U) 
     Example 552 
     Compound O9-9 
     8-(4-(Oxetan-3-yl)piperazin-1-yl)-11-oxo-9-(prop-1-ynyl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O7-4 and oxetan-3-one. 
     LCMS: m/z 507 [M+H] +   
     HPLC retention time: 1.43 min (analysis condition S) 
     Example 553 
     Compound O10-1-1 
     Tert-butyl4-(3-cyano-9-ethyl-11-oxo-2′,3′,5,5a,5′,6′,11,11a-octahydrospiro[benzo[b]carbazole-6,4′-pyran]-8-yl)piperazine-1-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound O7-5. 
     LCMS: m/z 541 [M+H] +   
     HPLC retention time: 3.08 min (analysis condition S) 
     Example 554 
     Compound O10-1-2 
     9-Ethyl-11-oxo-8-(piperazin-1-yl)-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound O10-1-1. 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 1.42 min (analysis condition S) 
     Example 555 
     Compound O10-2 
     9-Ethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound O9-8. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.23-8.21 (1H, m), 8.02-8.00 (1H, m), 7.88-7.86 (1H, m), 7.39-7.36 (2H, m), 4.63-4.59 (2H, m), 3.89-3.85 (2H, m), 3.60-3.56 (6H, m), 3.22-3.19 (4H, m), 2.76-2.68 (4H, m), 2.37-2.32 (3H, m), 1.92-1.88 (2H, m), 1.75-1.72 (2H, m), 1.61-1.57 (2H, m), 1.27-1.25 (3H, m) 
     LCMS: m/z 525 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition S) 
     Example 556 
     Compound O10-3 
     9-Ethyl-8-(4-(oxetan-3-yl)piperazin-1-yl)-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O10-1-2 and oxetan-3-one. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.26 (1H, s), 8.39 (1H, d, 7.9 Hz), 8.09-8.07 (2H, m), 7.63 (1H, d, 8.5 Hz), 7.51 (1H, s), 4.60-4.50 (4H, m), 4.20-4.09 (4H, m), 3.56-3.51 (1H, m), 3.07-3.05 (4H, m), 2.76-2.70 (2H, m), 2.44-2.40 (2H, m), 2.02-1.98 (2H, m), 1.29-1.26 (4H, m) 
     LCMS: m/z 497 [M+H] +   
     HPLC retention time: 1.42 min (analysis condition S) 
     Example 557 
     Compound O10-4 
     8-(4-Cyclobutylpiperazin-1-yl)-9-ethyl-11-oxo-2′,3′,5,5′,6′,11-hexahydrospiro[benzo[b]carbazole-6,4′-pyran]-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O10-1-2 and cyclobutanone. 
     LCMS: m/z 495 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition S) 
     Example 558 
     Compound P1 (Intermediate) 
     8-Methoxy-6,6-dimethyl-2-nitro-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and 4-nitrophenylhydrazine. 
     LCMS: m/z 323 [M+H] +   
     HPLC retention time: 4.08 min (analysis condition W) 
     Example 559 
     Compound P2 (Intermediate) 
     8-Methoxy-6,6-dimethyl-2-nitro-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound P1. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.85 (1H, s), 9.03 (1H, d, J=1.9 Hz), 8.17-8.20 (2H, m), 7.71 (1H, d, J=9.1 Hz), 7.38 (1H, d, J=2.4 Hz), 7.12 (1H, dd, J=8.5, 2.4 Hz), 3.93 (3H, s), 1.79 (6H, s) 
     LCMS: m/z 337 [M+H] +   
     HPLC retention time: 3.55 min (analysis condition W) 
     Example 560 
     Compound P3 (Intermediate) 
     8-Hydroxy-6,6-dimethyl-2-nitro-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound P2. 
     LCMS: m/z 323 [M+H] +   
     HPLC retention time: 3.11 min (analysis condition W) 
     Example 561 
     Compound P4 (Intermediate) 
     4-(6,6-Dimethyl-2-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound P3. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 9.40 (1H, s), 9.37 (1H, s), 8.41 (1H, d, J=8.5 Hz), 8.24 (1H, d, J=11.0 Hz), 7.51 (1H, d, J=8.5 Hz), 7.13 (1H, s), 7.03 (1H, d, J=9.1 Hz), 4.61-4.71 (1H, m), 3.69-3.84 (2H, m), 3.35-3.49 (2H, m), 1.94-2.10 (2H, m), 1.75-1.93 (8H, m), 1.50 (9H, s) 
     LCMS: m/z 506 [M+H] +   
     HPLC retention time: 4.17 min (analysis condition W) 
     Example 562 
     Compound P5 
     2-Amino-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound P6. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.23 (1H, d, J=8.5 Hz), 7.68 (1H, d, J=2.4 Hz), 7.26 (1H, d, J=8.5 Hz), 7.24 (1H, d, J=2.4 Hz), 7.06 (1H, dd, J=8.5, 2.4 Hz), 6.80 (1H, dd, J=8.5, 2.4 Hz), 4.64-4.71 (1H, m), 3.06-3.15 (2H, m), 2.73-2.83 (2H, m), 2.02-2.13 (2H, m), 1.67-1.82 (8H, m) 
     LCMS: m/z 506 [M+H] +   
     HPLC retention time: 4.17 min (analysis condition W) 
     Example 563 
     Compound P6 (Intermediate) 
     4-(2-Amino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     To the ethanol (8 ml) suspension of 4-(6,6-dimethyl-2-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound P4, 103 mg, 0.204 mmol), iron powder (228 mg, 20 eq.), ammonium chloride (109 mg, 10 eq.), and distilled water (4 ml) were added and the mixture was stirred at 90° C. for 30 min. Upon the completion of the reaction, insoluble matters were filtered off, and the filtrate was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (115 mg, 57%). 
     LCMS: m/z 476 [M+H] +   
     HPLC retention time: 2.82 min (analysis condition W) 
     Example 564 
     Compound P7 (Intermediate) 
     4-(2-Methanesulfonylamino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     To the pyridine (2 ml) solution of 4-(2-amino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound P6, 50 mg, 0.105 mmol), mesyl chloride (9 μl, 1.2 eq.) was added and stirred at room temperature for 30 min. Upon the completion of the reaction, the reaction solution was concentrated under reduced pressure to obtain the title compound as an unpurified product. 
     LCMS: m/z 554 [M+H] +   
     HPLC retention time: 3.60 min (analysis condition W) 
     Example 565 
     Compound P8 
     N-[6,6-Dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-2-yl]-methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound P7. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.25 (1H, d, J=8.5 Hz), 8.16 (1H, d, J=1.8 Hz), 7.46 (1H, d, J=9.1 Hz), 7.27-7.29 (2H, m), 7.09 (1H, dd, J=9.1, 1.8 Hz), 4.67-4.75 (1H, m), 3.09-3.18 (2H, m), 2.95 (3H, s), 2.77-2.87 (2H, m), 1.70-1.84 (8H, m) 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition W) 
     Example 566 
     Compound Q3 (Intermediate) 
     2-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and 3-cyano-4-fluorophenylhydrazine. 
     LCMS: m/z 321 [M+H] +   
     HPLC retention time: 4.13 min (analysis condition W) 
     Example 567 
     Compound Q4 (intermediate) 
     2-Fluoro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound Q3. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.89 (1H, s), 8.16 (1H, d, J=8.5 Hz), 8.07 (1H, d, J=4.9 Hz), 8.04 (1H, d, J=9.8 Hz), 7.36 (1H, d, J=2.4 Hz), 7.10 (1H, dd, J=8.5, 2.4 Hz), 3.91 (3H, s), 1.78 (3H, s) 
     LCMS: m/z 335 [M+H] +   
     HPLC retention time: 3.61 min (analysis condition W) 
     Example 568 
     Compound Q5 (intermediate) 
     2-Fluoro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound Q4. 
     LCMS: m/z 321 [M+H] +   
     HPLC retention time: 3.16 min (analysis condition W) 
     Example 569 
     Compound Q6 (intermediate) 
     4-(3-Cyano-2-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound Q5. 
     LCMS: m/z 504 [M+H] +   
     HPLC retention time: 4.25 min (analysis condition W) 
     Example 570 
     Compound Q7 
     8-(2-Diethylamino-ethoxy)-2-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound Q5. 
       1 H-NMR (400 MHz, CD 3 OD) δ: 8.25 (1H, d, J=8.5 Hz), 8.09 (1H, d, J=9.8 Hz), 7.83 (1H, d, J=5.5 Hz), 7.30 (1H, d, J=2.4 Hz), 7.09 (1H, dd, J=8.5, 2.4 Hz), 4.26 (2H, t, J=5.7 Hz), 2.98 (2H, t, J=5.7 Hz), 2.72 (4H, q, J=7.2 Hz), 1.81 (6H, s), 1.13 (6H, t, J=7.2 Hz) 
     LCMS: m/z 420 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition W) 
     Example 571 
     Compound Q8 
     2-Fluoro-6,6-dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound Q6. 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.11 (1H, d, J=8.5 Hz), 7.98 (1H, d, J=5.5 Hz), 7.96 (1H, d, J=9.8 Hz), 7.29 (1H, s), 7.08 (1H, d, J=8.5 Hz), 4.58-4.69 (1H, m), 2.93-3.05 (2H, m), 2.60-2.69 (2H, m), 1.94-2.03 (2H, m), 1.74 (6H, s), 1.45-1.57 (2H, m) 
     LCMS: m/z 404 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition W) 
     Example 572 
     Compound R2 
     2-Fluoro-3-hydrazinylbenzonitrile 
     
       
         
         
             
             
         
       
     
     3-Amino-2-fluoro-benzonitrile (100 mg, 0.735 mmol) was dissolved in water (0.94 mL), added with conc. hydrochloric acid (0.74 mL) at 0° C., and then further added with an aqueous solution (0.294 mL) of sodium nitrite (61 mg, 0.882 mmol). The resulting mixture was stirred at 0° C. for 1 hr. To the reaction mixture, conc. hydrochloric acid solution (0.94 mL) of tin chloride (321 mg, 1.69 mmol) was added and stirred at room temperature for 1 hr. Thereafter, the reaction solution was neutralized with aqueous solution of sodium hydroxide, and extracted with dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the residues were obtained after concentration under reduced pressure to give the target compound as a crude product. 
     Example 573 
     Compound R3 
     4-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared as a crude product from Compound A2 and Compound R2. 
     Example 574 
     Compound R4 
     4-Fluoro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound R3. 
     LCMS: m/z 335 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition U) 
     Example 575 
     Compound R5 
     4-Fluoro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound R4. 
     LCMS: m/z 321 [M+H] +   
     HPLC retention time: 2.32 min (analysis condition U) 
     Example 576 
     Compound R6 
     8-(2-Diethylamino-ethoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound R5. 
     LCMS: m/z 420 [M+H] +   
     HPLC retention time: 1.51 min (analysis condition S) 
     Example 577 
     Compound R7 
     Trifluoromethanesulfonic acid 3-cyano-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound R5. 
     LCMS: m/z 453 [M+H] +   
     HPLC retention time: 3.82 min (analysis condition Y) 
     Example 578 
     Compound R8-1 
     4-Fluoro-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound R7 and 4-pyrrolidin-1-yl-piperidine. 
     LCMS: m/z 457 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition U) 
     Example 579 
     Compound R8-2 
     4-Fluoro-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound R7. 
     LCMS: m/z 431 [M+H] +   
     HPLC retention time: 2.07 min (analysis condition U) 
     Example 580 
     Compound R9-1 
     8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared as a crude product from Compound R5 and (R)-(−)-2,2-dimethyl-1,3-dioxolan-4-methanol. 
     Example 581 
     Compound R9-2 
     8-((R)-2,3-Dihydroxy-propoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound R9-1 (9.9 mg, 80%). 
     LCMS: m/z 395 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition C) 
     Example 582 
     Compound S1-1 
     3-Chloro-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1 and Compound A4, the title compound was prepared as a crude product from Compound A2 and (3-chlorophenyl)-hydrazine hydrochloric acid salt. 
     Example 583 
     Compound S1-2 
     3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 99.1 mg, 0.485 mmol) and (3-chloro-4-methyl-phenyl)hydrazine hydrochloric acid salt (100.4 mg, 1.1 eq.) were dissolved in TFA (1 mL) and the mixture was irradiated with microwave at 80° C. for 10 min under nitrogen atmosphere. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate and saturated brine and dried over magnesium sulfate. After filtration and concentration under reduced pressure, the residues obtained therefrom were dissolved in THF (2 mL) and water (0.2 mL), added with DDQ (125.7 mg, 1.1 eq.), and stirred at room temperature overnight. The reaction solution was added with the mixture solvent of hexane and ethyl acetate, and the starting-point components were removed by dry type silica gel column. The eluent was concentrated under reduced pressure, and the resulting residues were purified by preparative TLC (methanol/dichloromethane) to obtain the title compound (19.4 mg, 12%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.2 (1H, s), 8.15 (1H, d, J=8.8 Hz), 8.12 (1H, s), 7.52 (1H, s), 7.32 (1H, s), 7.07 (1H, dd, J=2.4, 8.8 Hz), 3.90 (3H, s), 2.45 (3H, s), 1.73 (6H, s), 
     LCMS: m/z 340 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition F) 
     Example 584 
     Compound S1-3 
     3-Chloro-4-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and (3-chloro-2-fluoro-phenyl)-hydrazine. 
     LCMS: m/z 344, 346 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition S) 
     Example 585 
     Compound S1-4 
     9-Bromo-3-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 0.2 g, 0.71 mmol) and 3-chlorophenylhydrazine hydrochloric acid salt (0.17 g, 1.3 eq.) were dissolved in acetic acid (0.5 mL). Under nitrogen atmosphere, the reaction solution was stirred at 90° C. for 8 hr. After cooling to room temperature, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate and saturated brine and dried over magnesium sulfate. After filtration and concentration under reduced pressure, the residues obtained therefrom were dissolved in THF (3 mL) comprising 10% water, added with DDQ (227 mg, 3 eq.) at room temperature, and the mixture was stirred at room temperature for 2 hr. The reaction solution was added with the mixture liquid of THF/diethyl ether (1:1) and washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine. After drying with sodium sulfate, the mixture was filtered and the resulting residues obtained after concentration under reduced pressure were washed with the mixture liquid of hexane/diethyl ether (1:1) to obtain the title compound (brown powder, 86 mg). 
     LCMS: m/z 404, 406, 408 [M+H] +   
     HPLC retention time: 3.02 min (analysis condition C) 
     Example 586 
     Compound 52-1 
     3-Chloro-8-hydroxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound S1-1. 
     LCMS: m/z 312 [M+H] +   
     HPLC retention time: 4.18 min (analysis condition H) 
     Example 587 
     Compound S2-2 
     3-Chloro-8-hydroxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-2, 18.9 mg, 0.0556 mmol) and pyridinium chloride (220 mg, 34 eq.) were stirred at 185° C. for 2.5 hr. After cooling, the reaction solution was added with water and ethyl acetate, and the organic layer was washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound as a crude product. 
     Example 588 
     Compound S2-3 
     3-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Chloro-4-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound 51-3, 220.0 mg, 0.640 mmol) and pyridinium chloride (800 mg, 6.922 mmol) were mixed with each other, heated to 160° C., and then stirred for 20 hr. The reaction solution was added with water. As a result, black solid was obtained as a precipitate, which was then filtered and subjected to purification by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (139.4 mg, 66%). 
     LCMS: m/z 330 [M+H] +   
     HPLC retention time: 2.60 min (analysis condition F) 
     Example 589 
     Compound S2-4 
     9-Bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound S1-4. 
     LCMS: m/z 390, 392, 394 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition C) 
     Example 590 
     Compound S3 
     3-Chloro-8-(2-diethylaminoethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (CH5263231-000) 
     
       
         
         
             
             
         
       
     
     3-Chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-1, 10 mg, 0.03207 mmol) was dissolved in DMF (0.1 mL), added with (2-chloroethyl)diethylamine (5.5 mg, 0.03207 mmol) and cesium carbonate (20.9 mg, 0.06414 mmol), and stirred at 80° C. for 2 hr. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by NH silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (11.6 mg, 76%). 
     LCMS: m/z 411 [M+H] +   
     HPLC retention time: 4.49 min (analysis condition H) 
     Example 591 
     Compound S4 
     3-Chloro-2,6,6-trimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Crude product of Compound S2-2 was dissolved in THF (0.4 mL) under nitrogen atmosphere, together with THF (0.2 mL) solution of triphenylphosphine (18.9 mg, 1.3 eq.) and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (17 mg, 1.2 eq.). DEAD (40% toluene solution, 0.0031 mL, 1.2 eq.) was added to the solution, which was then stirred at room temperature for 40 min and at 40° C. for 4 hr. The reaction solution was added with triphenylphosphine (18.9 mg, 1.3 eq.) and DEAD (40% toluene solution, 0.002 mL, 0.8 eq.) and stirred at 40° C. overnight. The reaction solution was added with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, and filtered. The residues obtained after concentration under reduced pressure were purified by preparative TLC (ethyl acetate/hexane) to obtain the crude product of 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-chloro-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (12.6 mg). 
     The resultant was dissolved in THF (0.15 mL) and methanol (0.03 mL) under nitrogen atmosphere, added with 0.5 M sulfuric acid (0.05 mL) and stirred at 60° C. for 3 hr. After cooling, diethyl ether was added and sodium hydrogen carbonate (8.4 mg) and water were further added thereto. The organic layer was washed with saturated brine. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over magnesium sulfate, and filtered. The solid obtained from the concentration under reduced pressure was washed with dichloromethane to obtain the target compound (white solid, 5.3 mg, 22%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.18 (1H, s), 8.14 (1H, d, J=8.8 Hz), 8.12 (1H, s), 7.52 (1H, s), 7.31 (1H, d, J=2.4 Hz), 7.06 (1H, dd, J=2.4, 8.8 Hz), 4.78 (1H, d, J=5.9 Hz), 4.60 (1H, d, J=5.9 Hz), 4.52 (1H, t, J=5.4 Hz), 4.18-4.22 (1H, m), 4.02-4.06 (1H, m), 3.85-3.95 (1H, m), 3.50-3.60 (2H, m), 3.40-3.46 (1H, m), 2.45 (3H, s), 1.73 (3H, s), 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition F) 
     Example 592 
     Compound S5 
     3-Chloro-8-ethoxy-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound S6. 
     LCMS: m/z 358 [M+H] +   
     HPLC retention time: 3.16 min (analysis condition F) 
     Example 593 
     Compound S6 
     3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-3, 20.0 mg, 0.061 mmol) was dissolved in THF (0.25 mL), added with ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (9.8 μL, 0.079 mmol), triphenylphosphine (20.7 mg, 0.079 mmol) and diethyl azodicarboxylic acid (35.9 μl, 0.079 mmol), and then stirred at 40° C. for 5 hr. The reaction solution was concentrated under reduced pressure, and the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the intermediate, 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one. This compound was dissolved in THF (0.10 mL) and MeOH (0.08 ml), added with sulfuric acid (0.5 M, 0.045 ml), and then stirred at 60° C. for 1 hr. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The yellow solid obtained after concentration under reduced pressure was washed with methylene chloride/hexane solvent and filtered to obtain the title compound (4.3 mg, 18%). 
     LCMS: m/z 404 [M+H] +   
     HPLC retention time: 2.34 min (analysis condition F) 
     Example 594 
     Compound S7-1 
     3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 9-bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-4, 76 mg, 0.2 mmol) and triphenylphosphine (69 mg, 1.3 eq.) were added with THF (2 ml), and ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (35 mg, 1.3 eq.) and 2.19 N toluene solution (118 μL, 1.3 eq.) of diethyl azodicarboxylic acid were added dropwise thereto, followed by stirring at 50° C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine, dried over sodium sulfate and filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to give a solid, which was then washed with dichloromethane to obtain the title compound (brown powder, 53 mg). 
     LCMS: m/z 504, 506, 508 [M+H] +   
     HPLC retention time: 3.17 min (analysis condition C) 
     Example 595 
     Compound S7-2 
     9-Bromo-3-chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-1, 56 mg, 0.11 mmol) was dissolved in methanol (5 mL), added with 1 N hydrochloric acid (0.2 ml), and stirred at 50° C. for 2 hr. After cooling, the reaction solution was concentrated under reduced pressure and the resulting residues were added with methanol to obtain a precipitated solid, which was then filtered to obtain the title compound (white powder, 26 mg). 
     LCMS: m/z 464, 466, 468 [M+H] +   
     HPLC retention time: 2.77 min (analysis condition C) 
     Example 596 
     Compound S7-3 
     3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 9-bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-4, 112 mg, 0.29 mmol) and triphenylphosphine (227 mg, 3 eq.) were added with THF (2 ml), and ((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (114 mg, 3 eq.) and 2.19 N toluene solution (0.4 mL, 3 eq.) of diethyl azodicarboxylic acid were added dropwise thereto, followed by stirring at 40° C. for 12 hr under nitrogen atmosphere. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to obtain the title compound (white powder, 100 mg). 
     LCMS: m/z 504, 506, 508 [M+H] +   
     HPLC retention time: 3.15 min (analysis condition C) 
     Example 597 
     Compound S7-4 
     9-Bromo-3-chloro-8-((S)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound S7-2, the title compound was prepared from Compound S7-3. 
     LCMS: m/z 464, 466, 468 [M+H] +   
     HPLC retention time: 2.77 min (analysis condition C) 
     Example 598 
     Compound S8-1 
     9-Hydroxy-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     9-Bromo-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-1, 30 mg, 0.06 mmol) was dissolved in the mixture solvent of water dioxane (1:1) (0.5 mL), added with tris(benzylidenacetone dipalladium)chloroform complex (3.1 mg, 0.05 eq.), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (2.5 mg, 0.1 eq.) and KOH (0.5 N aqueous solution 180 μL, 1.5 eq.), and stirred at 60° C. for 12 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were purified by HPLC to obtain the title compound (white solid, 4.6 mg). 
     LCMS: m/z 442, 444 [M+H] +   
     HPLC retention time: 2.78 min (analysis condition C) 
     Example 599 
     Compound S8-2 
     3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound S7-2, the title compound was prepared from Compound S8-1. 
     LCMS: m/z 402, 404 [M+H] +   
     HPLC retention time: 0.90 min (analysis condition I) 
     Example 600 
     Compound S9-1 
     8-Hydroxy-6,6-dimethyl-11-oxo-9-(1H-tetrazol-5-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Bromo-3-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-4, 150 mg, 0.37 mMol) was dissolved in NMP, added with CuCN (100 mg, 3 eq.), and stirred at 210° C. for 1.5 hr under irradiation with microwave. After cooling, the reaction solution was added with water and ethyl acetate, and the precipitated solid was filtered to remove the solvent. The obtained residues were dissolved in DMF (1 ml), added with sodium azide (100 mg, 8 eq.) and ammonium chloride (5 mg), and then stirred at 120° C. for 24 hr in a sealed tube. After adding water, the insoluble matters were filtered and purified by HPLC to obtain the title compound (6.5 mg). 
     LCMS: m/z 371 [M+H] +   
     HPLC retention time: 2.22 min (analysis condition C) 
     Example 601 
     Compound S9-2 
     3-Chloro-8-hydroxy-6,6-dimethyl-9-(1H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as an intermediate for the synthesis of Compound S9-1. 
     LCMS: m/z 380, 382 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition C) 
     Example 602 
     Compound S10 
     3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     To the mixture of 9-bromo-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-1, 50 mg, 0.1 mmol), bis(acetonitrile) palladium (II) dichloride (2.6 mg, 0.01 eq.), cesium carbonate (195 mg, 6 eq.) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (14.3 mg, 0.03 eq.), acetonitrile (2 mL) was added and stirred at 80° C. for 12 hr. Tar-like residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (brown powder, 105 mg). The resulting 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (20 mg, 0.04 mmol) was dissolved in methanol (3 mL), added with 1 N hydrochloric acid (1 ml), and stirred at room temperature for 12 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were washed with methylene chloride to obtain the title compound (pale yellow powder, 5.2 mg). 
     LCMS: m/z 468, 470 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition C) 
     Example 603 
     Compound S11-1 
     3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-carbonitrile 
     
       
         
         
             
             
         
       
     
     3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-2, 17 mg, 37 μmol) was dissolved in DMA, added with CuCN (17 mg, 5 eq.), and stirred at 220° C. for 2 hr under irradiation with microwave. After cooling, the reaction solution was added with ethyl acetate, and the precipitated solid was filtered to remove the solvent. The resulting residues were purified by HPLC to obtain the title compound (4 mg). 
     LCMS: m/z 409, 411 [M+H] +   
     HPLC retention time: 2.65 min (analysis condition C) 
     Example 604 
     Compound S11-2 
     3-Chloro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound S11-1. 
     LCMS: m/z 337, 339 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition C) 
     Example 605 
     Compound T1-1 
     3-Bromo-6,6-dimethyl-8-[(R)-(tetrahydro-furan-3-yl) oxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and (S)-tetrahydro-furan-3-ol. 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 2.08 min (analysis condition D) 
     Example 606 
     Compound T1-2 
     6,6-Dimethyl-11-oxo-8-[(R)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound T1-1. 
     LCMS: m/z 373 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition A) 
     Example 607 
     Compound T2-1 
     3-Bromo-6,6-dimethyl-8-[(S)-(tetrahydro-furan-3-yl)oxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and (R)-tetrahydro-furan-3-ol. 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 6.12 min (analysis condition H) 
     Example 608 
     Compound T2-2 
     6,6-Dimethyl-11-oxo-8-[(S)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound T2-1. 
     LCMS: m/z 373 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition D) 
     Example 609 
     Compound T3-1 
     3-Bromo-6,6-dimethyl-8-(tetrahydro-pyran-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and tetrahydro-pyran-4-ol. 
     LCMS: m/z 440 [M+H] +   
     HPLC retention time: 8.07 min (analysis condition H) 
     Example 610 
     Compound T3-2 
     3-Bromo-5,6,6-trimethyl-8-(tetrahydro-pyran-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T3-1. 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 6.88 min (analysis condition H) 
     Example 611 
     Compound T4-1 
     3-Bromo-6,6-dimethyl-8-(2-phenyl-[1,3]dioxan-5-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 5-phenyl-[1,3]dioxan-2-ol. 
     LCMS: m/z 518 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition D) 
     Example 612 
     Compound T4-2 
     3-Bromo-8-(2-hydroxy-1-hydroxymethyl-ethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-13-2, the title compound was prepared from Compound T4-1. 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 4.64 min (analysis condition H) 
     Example 613 
     Compound T5-1 
     4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 539 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition D) 
     Example 614 
     Compound T5-2 
     4-(3-Bromo-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A10-1, the title compound was prepared from Compound T5-1. 
     LCMS: m/z 553 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition D) 
     Example 615 
     Compound T5-3 
     3-Bromo-5,6,6-trimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T5-2. 
     LCMS: m/z 453 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition D) 
     Example 616 
     Compound T5-4 
     3-Bromo-8-(1-methanesulfonyl-piperidin-4-yloxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-7, the title compound was prepared from Compound T5-3 and methanesulfonyl chloride. 
     LCMS: m/z 531 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition D) 
     Example 617 
     Compound T5-5 
     8-(1-Acetyl-piperidin-4-yloxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T5-3 and acetic anhydride. 
     LCMS: m/z 482 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition D) 
     Example 618 
     Compound T6-1 
     3-Bromo-6,6-dimethyl-8-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yloxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and trifluoroacetic anhydride. 
     LCMS: m/z 535 [M+H] +   
     HPLC retention time: 2.53 min (analysis condition D) 
     Example 619 
     Compound T6-2 
     3-Bromo-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-6,6-dimethyl-8-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yloxy]-5,6-dihydro-benzo[b]carbazol-11-one (Compound T6-1, 28.0 mg, 52.3 μmol) was dissolved in THF (1.00 mL) and methanol (0.50 mL), added with aqueous solution of potassium hydroxide (1.00 mL, 20 wt %), and stirred at room temperature for 1 hr. The reaction solution was added to water, and extracted with mixture solution of chloroform and methanol, and dried over sodium sulfate. Then, after filtering and concentration under reduced pressure, 3-bromo-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one was obtained as a crude product. 
     LCMS: m/z 439 [M+H] +   
     HPLC retention time: 1.83 min (analysis condition D) 
     Example 620 
     Compound T6-3 
     3-Bromo-8-(1-methanesulfonyl-piperidin-4-yloxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and mesyl chloride. 
     LCMS: m/z 517 [M+H] +   
     HPLC retention time: 2.23 min (analysis condition D) 
     Example 621 
     Compound T6-4 
     8-(1-Acetyl-piperidin-4-yloxy)-3-bromo-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and acetic anhydride. 
     LCMS: m/z 496 [M+H] +   
     HPLC retention time: 2.27 min (analysis condition D) 
     Example 622 
     Compound T7-1 
     3-Bromo-8-isopropoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound T4-1. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 3.18 min (analysis condition F) 
     Example 623 
     Compound T7-2 
     3-Bromo-8-isopropoxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T7-1. 
     LCMS: m/z 413 [M+H] +   
     HPLC retention time: 2.70 min (analysis condition D) 
     Example 624 
     Compound T8-1 
     3-Bromo-5,6,6-trimethyl-8-(2-phenyl-[1,3]dioxan-5-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T4-1. 
     LCMS: m/z 532 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition D) 
     Example 625 
     Compound T8-2 
     3-Bromo-8-(2-hydroxy-1-hydroxymethyl-ethoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-13-2, the title compound was prepared from Compound T4-1. 
     LCMS: m/z 444 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition D) 
     Example 626 
     Compound T9 
     N-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-ethyl]-acetamide 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and (N-(2-chloro-ethyl)-acetamide. 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition D) 
     Example 627 
     Compound T10 
     3-Bromo-6,6-dimethyl-8-(oxetan-3-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and toluene-4-sulfonic acid oxetan-3-yl ester. 
     LCMS: m/z 412 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition D) 
     Example 628 
     Compound T11 
     3-Bromo-8-(4-hydroxy-tetrahydro-furan-3-yl oxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, tetrahydro-furo[3,4-d][1,3,2]dioxathiol 2,2-dioxide (71.5 mg, 0.420 mmol) was dissolved in DMF (1.40 mL), added with 3-bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 50.0 mg, 0.140 mmol) and cesium carbonate (228 mg, 0.700 mmol), and stirred at 80° C. for 15 hr. Subsequently, sulfuric acid (0.10 mL, 18 M), THF (3.00 mL) and water (0.50 mL) were added to the mixture, which was then stirred at room temperature for 24 hr and further at 60° C. for 24 hr. The reaction solution was added to water, extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, and saturated brine, and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were washed with dichloromethane and purified by NH silica gel column chromatography (ethyl acetate/THF) to obtain the target compound (44.7 mg, 72%). 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition D) 
     Example 629 
     Compound T12-1 
     Acetic acid (2S,3R,4S,5R,6R)-4,5-diacetoxy-6-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-2-methoxy-tetrahydro-pyran-3-yl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and methyl 2,3,4-tri-O-acetyl-a-D-glucopyranoside. 
     LCMS: m/z 658 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition D) 
     Example 630 
     Compound T12-2 
     3-Bromo-6,6-dimethyl-8-((2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxy-tetrahydro-pyran-2-yl methoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to acetic acid (2S,3R,4S,5R,6R)-4,5-diacetoxy-6-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-2-methoxy-tetrahydro-pyran-3-yl ester (Compound T12-1, 34.0 mg, 51.63 μmol), methanol solution (2.50 mL, 2 M) of ammonia was added, and the mixture was stirred at room temperature for 21 hr. The reaction solution was concentrated under reduced pressure, and the resulting resides were washed with diethyl ether to obtain the target compound (25.7 mg, 94%). 
     LCMS: m/z 532 [M+H] +   
     HPLC retention time: 2.42 min (analysis condition D) 
     Example 631 
     Compound T13-1 
     (3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and bromo-acetic acid tert-butyl ester. 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 2.53 min (analysis condition D) 
     Example 632 
     Compound T13-2 
     (3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic acid 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T13-1. 
     LCMS: m/z 414 [M+H] +   
     HPLC retention time: 1.50 min (analysis condition D) 
     Example 633 
     Compound T13-3 
     2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-N-(3-ethyl-3-hydroxy-pentyl)-acetamide 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, (3-azide-1,1-diethyl-propoxy)-trimethyl-silane (16.6 mg, 72.42 μmol) was dissolved in toluene (0.48 mL), added with 3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic acid (20.0 mg, 48.28 μmol) and Molecular Sieves 4 angstrom, and the mixture was stirred at room temperature for 5 min. Thereafter, the mixture was added with trimethylphosphine (10.2 μL, 96.56 μmol) and stirred at 80° C. for 22 hr. The reaction solution was added to hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, saturated brine and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound (0.7 mg, 3%). 
     LCMS: m/z 527 [M+H] +   
     HPLC retention time: 2.93 min (analysis condition D) 
     Example 634 
     Compound T13-4 
     4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-10, the title compound was prepared from Compound T13-2 and 1-(tert-butoxycarbonyl)piperazine. 
     LCMS: m/z 582 [M+H] +   
     HPLC retention time: 2.32 min (analysis condition D) 
     Example 635 
     Compound T13-5 
     3-Bromo-6,6-dimethyl-8-(2-oxo-2-piperazin-1-yl-ethoxy)-5,6-dihydro-benzo[b]carbazol-11-one hydrochloric acid salt 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T13-4. 
     LCMS: m/z 482 [M+H] +   
     HPLC retention time: 1.75 min (analysis condition D) 
     Example 636 
     Compound T13-6 
     3-Bromo-8-[2-(4-methanesulfonyl-piperazin-1-yl)-2-oxo-ethoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and methanesulfonyl chloride. 
     LCMS: m/z 560 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition D) 
     Example 637 
     Compound T13-7 
     3-Bromo-6,6-dimethyl-8-{2-oxo-2-[4-(propane-2-sulfonyl)-piperazin-1-yl]-ethoxy}-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and isopropylsulfonyl chloride. 
     LCMS: m/z 588 [M+H] +   
     HPLC retention time: 2.47 min (analysis condition D) 
     Example 638 
     Compound T13-8 
     8-[2-(4-Acetyl-piperazin-1-yl)-2-oxo-ethoxy]-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and acetic anhydride. 
     LCMS: m/z 524 [M+H] +   
     HPLC retention time: 1.85 min (analysis condition D) 
     Example 639 
     Compound T13-9 
     3-Bromo-6,6-dimethyl-8-[2-(4-oxetan-3-yl-piperazin-1-yl)-2-oxo-ethoxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T13-5 and 3-oxetanone. 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition D) 
     Example 640 
     Compound T13-10 
     4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl-oxy)-acetyl]-piperazine-1-sulfonic acid methylamide 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and 2-oxo-oxazolidine-3-sulfonic acid methylamide. 
     LCMS: m/z 575 [M+H] +   
     HPLC retention time: 2.29 min (analysis condition A) 
     Example 641 
     Compound T14-1 
     4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 1-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine. 
     LCMS: m/z 553 [M+H] +   
     HPLC retention time: 2.80 min (analysis condition D) 
     Example 642 
     Compound T14-2 
     3-Bromo-6,6-dimethyl-8-(piperidin-4-ylmethoxy)-5,6-dihydro-benzo[b] carbazol-11-one hydrochloric acid salt 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T14-1. 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition D) 
     Example 643 
     Compound T14-3 
     3-Bromo-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T14-2 and 3-oxetanone. 
       1 H-NMR (400 MHz, CDCl 3 ) δ: 9.24 (1H, s), 8.37 (1H, d, 8.8 Hz), 8.30 (1H, d, 8.3 Hz), 7.57 (1H, d, 1.5 Hz), 7.41 (1H, dd, 8.3, 1.5 Hz), 7.08 (1H, d, 2.4 Hz), 6.98 (1H, dd, 8.8, 2.4 Hz) 4.60-4.95 (7H, m), 3.93 (2H, d, 5.9 Hz), 3.50 (1H, m), 2.83 (2H, d, 11.2 Hz), 1.89 (4H, m), 1.78 (6H, s), 
     LCMS: m/z 509 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition A) 
     Example 644 
     Compound T14-4 
     8-(1-Acetyl-piperidin-4-ylmethoxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and acetic anhydride. 
     LCMS: m/z 495 [M+H] +   
     HPLC retention time: 2.53 min (analysis condition A) 
     Example 645 
     Compound T14-5 
     3-Bromo-8-(1-methanesulfonyl-piperidin-4-ylmethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and methanesulfonyl chloride. 
     LCMS: m/z 531 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition D) 
     Example 646 
     Compound T14-6 
     3-Bromo-6,6-dimethyl-8-[1-(propane-2-sulfonyl)-piperidin-4-ylmethoxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and isopropylsulfonyl chloride. 
     LCMS: m/z 559 [M+H] +   
     HPLC retention time: 2.58 min (analysis condition D) 
     Example 647 
     Compound T14-7 
     3-[4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-piperidin-1-yl]-azetidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T14-2 and 3-oxo-azetidine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 608 [M+H] +   
     HPLC retention time: 2.29 min (analysis condition A) 
     Example 648 
     Compound T14-8 
     8-(1-Azetidin-3-yl-piperidin-4-ylmethoxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T14-7. 
     LCMS: m/z 508 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition A) 
     Example 649 
     Compound T14-9 
     3-Bromo-8-[1-(1-methanesulfonyl-azetidin-3-yl)-piperidin-4-ylmethoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-8 and mesyl chloride. 
     LCMS: m/z 586 [M+H] +   
     HPLC retention time: 2.06 min (analysis condition A) 
     Example 650 
     Compound T14-10 
     8-[1-(1-Acetyl-azetidin-3-yl)-piperidin-4-ylmethoxy]-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same met o as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-8 and acetic anhydride. 
     LCMS: m/z 550 [M+H] +   
     HPLC retention time: 2.53 min (analysis condition A) 
     Example 651 
     Compound T15-1 
     4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-ethyl]-piperidine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and N-(tert-butoxycarbonyl)-4-piperidine ethanol. 
     LCMS: m/z 567 [M+H] +   
     HPLC retention time: 2.29 min (analysis condition D) 
     Example 652 
     Compound T15-2 
     3-Bromo-6,6-dimethyl-8-(2-piperidin-4-yl-ethoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T15-1. 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition D) 
     Example 653 
     Compound T15-3 
     3-Bromo-6,6-dimethyl-8-[2-(1-oxetan-3-yl-piperidin-4-yl)-ethoxy]-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T15-2 and 3-oxetanone. 
     LCMS: m/z 523 [M+H] +   
     HPLC retention time: 2.28 min (analysis condition D) 
     Example 654 
     Compound T16-1 
     4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 3-hydroxy-1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester. 
     LCMS: m/z 595 [M+H] +   
     HPLC retention time: 3.08 min (analysis condition A) 
     Example 655 
     Compound T16-2 
     3-Bromo-6,6-dimethyl-8-(1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T16-1. 
     LCMS: m/z 496 [M+H] +   
     HPLC retention time: 1.99 min (analysis condition A) 
     Example 656 
     Compound T16-3 
     3-Bromo-8-(8-methanesulfonyl-1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T16-2 and mesyl chloride. 
     LCMS: m/z 573 [M+H] +   
     HPLC retention time: 2.56 min (analysis condition A) 
     Example 657 
     Compound T16-4 
     3-Bromo-6,6-dimethyl-8-(8-oxetan-3-yl-1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T16-2 and 3-oxetanone. 
     LCMS: m/z 551 [M+H] +   
     HPLC retention time: 2.01 min (analysis condition A) 
     Example 658 
     Compound T17-1 
     3,7,9-Tribromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-[1,3]dithian-2-ylidene-piperidine-1-carboxylic acid tert-butyl ester (100 g, 0.332 mmol) was dissolved in dichloromethane (2.50 mL), added with trifluoromethanesulfonic acid (30.8 μL, 0.348 mmol) at −20° C., and stirred at room temperature for 30 min. The reaction solution was cooled to −70° C., and then added dropwise with the dichloromethane (2.50 mL) solution of 3-bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 177 mg, 0.498 mmol) and triethylamine (78.6 μL, 0.564 mmol). Thereafter, triethylamine hydrotrifluoric acid salt (262 μL, 1.610 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (460 mg, 1.610 mmol) were added thereto and stirred at −70° C. for 1 hr. The reaction solution was added to aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, saturated brine and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) and aminosilica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (42.0 mg, 25%). 
     LCMS: m/z 511 [M+H] +   
     HPLC retention time: 6.34 min (analysis condition B) 
     Example 659 
     Compound T17-2 
     3,7,9-Tribromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A17-1 and (S)-(+)-2,2-dimethyl-1,3-dioxolan-4-methanol. 
     LCMS: m/z 625 [M+H] +   
     HPLC retention time: 3.41 min (analysis condition A) 
     Example 660 
     Compound T17-3 
     3,7,9-Tribromo-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T17-2. 
     LCMS: m/z 585 [M+H] +   
     HPLC retention time: 2.44 min (analysis condition A) 
     Example 661 
     Compound T18-1 
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 18.0 mg, 50.5 μmol) was dissolved in DMF (0.18 mL), added with toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester (14.5 mg, 0.0505 mmol) and potassium carbonate (10.0 mg, 0.07575 mmol), and the mixture was stirred at 70° C. for 3 days. The reaction solution was added to water, extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by preparative TLC (methylene chloride/methanol) to obtain the title compound (16.6 mg, 70%). 
     LCMS: m/z 470 [M+H] +   
     HPLC retention time: 3.01 min (analysis condition F) 
     Example 662 
     Compound T18-2 
     3-Bromo-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T18-1. 
     LCMS: m/z 430 [M+H] +   
     HPLC retention time: 4.72 min (analysis condition H) 
     Example 663 
     Compound T19-1-1 
     3-Bromo-8-methoxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound A4. 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 2.84 min (analysis condition D) 
     Example 664 
     Compound T19-1 
     3-Bromo-8-hydroxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound T19-1-1. 
     LCMS: m/z 370 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition D) 
     Example 665 
     Compound T19-2 
     3-Bromo-8-(2-diethylaminoethoxy)-6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 (9.8 mg, 36%). 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 1.96 min (analysis condition D) 
     Example 666 
     Compound T19-3 
     3-Bromo-8-(2-diethylaminoethoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound T19-1. 
     LCMS: m/z 469 [M+H] +   
     HPLC retention time: 2.09 min (analysis condition D) 
     Example 667 
     Compound T20 
     5-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-pentanoic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, Compound A5-1 and methyl 5-bromovalerate were reacted, added with 1 N NaOH (140 L), and then stirred at room temperature for 2 hr. The reaction mixture was added with 2 N HCl (70 μL), and concentrated under reduced pressure. The resulting residues were purified by preparative TLC (methylene chloride:methanol=15:1) to obtain 7 mg (55%). 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 5.88 min (analysis condition H) 
     Example 668 
     Compound T21 
     (R)-5-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-4-hydroxy-pentanoic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound T20, the title compound was prepared from the reaction between Compound A5-1 and toluene-4-sulfonic acid (R)-5-oxo-tetrahydrofuran-2-yl methyl ester. 
     LCMS: m/z 471 [M+H] +   
     HPLC retention time: 4.57 min (analysis condition H) 
     Example 669 
     Compound T22-0 
     [5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol 
     
       
         
         
             
             
         
       
     
     To THF (50 mL), NaH (1.41 g, 0.032 mmol) was added at room temperature, followed by addition of ((4R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (5.0 g, 0.031 mmol) at room temperature. The mixture was stirred at room temperature for 1 hr. After that, TBSCl (5.11 g, 0.034 mmol) was added at room temperature and stirred at room temperature overnight. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (8.21 g, 96%). 
       1 H-NMR (270 MHz, DMSO-d 6 ) δ: 3.64-4.98 (6H, m), 2.37 (1H, m), 1.41 (3H, s), 1.40 (3H, s), 0.90 (9H, s), 0.08 (6H, s) 
     Example 670 
     Compound T22-1 
     3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and [5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (Compound T22-0) (704 mg, 80%). 
     LCMS: m/z 614 [M+H] +   
     HPLC retention time: 4.00 min (analysis condition F) 
     Example 671 
     Compound T22-1-1 
     3-Bromo-8-((1R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the DMF (0.4 mL) suspension of 3-bromo-8-[(1R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 50.3 mg, 0.0818 mmol) and copper (I) iodide (34 mg), sodium methoxide (1 M methanol solution, 0.82 mL, 0.818 mmol) was added and the mixture was stirred for 6 hr and 45 min at ambient temperature of 90° C. After cooling to room temperature, the reaction mixture was added with diethyl ether and ethyl acetate, and the insoluble matters were removed by Celite filtration. The concentrated residues were added with diethyl ether, hexane, ethyl acetate and water, and then the mixture was extracted twice with diethyl ether. The organic layer was washed with water and subsequently with brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by preparative TLC (Merck60 F 254 , 0.5 mm) {solution for elution:hexane/ethyl acetate (1:2)} to obtain the title compound (colorless oily substance, 22.6 mg, 55%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.44-8.38 (1H, b), 8.39 (1H, d, 8.6 Hz), 8.31 (1H, d, 8.2 Hz), 7.60 (1H, d, 1.3 Hz), 7.44 (1H, dd, 8.2 Hz, 1.3 Hz), 7.12 (1H, d, 2.3 Hz), 7.02 (1H, dd, 8.6 Hz, 2.3 Hz), 4.41-4.10 (4H, m), 4.00-3.88 (1H, m), 3.86-3.76 (1H, m), 1.78 (6H, s), 1.50 (3H, s), 1.49 (3H, s) 
     LCMS: m/z 500 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition C) 
     Example 672 
     Compound T22-1-2 
     Acetic acid (3R,4R)-5-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxymethyl)-2,2-dimethyl[1,3]dioxolan-4-yl methyl ester 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of T22-1-1 (white solid, 17.8 mg, 40%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.92-8.80 (1H, b), 8.40 (1H, d, 8.9 Hz), 8.31 (1H, d, 8.6 Hz), 7.58 (1H, d, 1.7 Hz), 7.43 (1H, dd, 8.6 Hz, 1.7 Hz), 7.14 (1H, d, 2.3 Hz), 7.02 (1H, dd, 8.9 Hz, 2.3 Hz), 4.51-4.38 (1H, m), 4.34-4.16 (4H, m), 2.13 (3H, s), 1.78 (6H, s), 1.50 (6H, s) 
     LCMS: m/z 542 [M+H] +   
     HPLC retention time: 3.00 min (analysis condition C) 
     Example 673 
     Compound T22-2 
     3-Bromo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-1 (2.83 g, 95%). 
     LCMS: m/z 460 [M+H] +   
     HPLC retention time: 4.50 min (analysis condition H) 
     Example 674 
     Compound T22-3 
     3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared from Compound T22-1. 
     LCMS: m/z 628 [M+H] +   
     HPLC retention time: 4.74 min (analysis condition F) 
     Example 675 
     Compound T22-4 
     3-Bromo-8-((2R,3R)-2,3-dihydroxy-pentyloxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-3. 
     LCMS: m/z 475 [M+H] +   
     HPLC retention time: 4.86 min (analysis condition H) 
     Example 676 
     Compound T22-5 
     {3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic acid methyl ester 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 3-bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 40.0 mg, 65.2 μmol) was dissolved in DMF (0.20 mL), added at 0° C. with methyl bromoacetate (30.5 μL, 134.5 μmol) and sodium hydride (4.5 mg, 132 μmol), and then stirred at room temperature for 2 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (44.5 mg, 85%). 
     LCMS: m/z 686 [M+H] +   
     HPLC retention time: 3.35 min (analysis condition D) 
     Example 677 
     Compound T22-6 
     {3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic acid 
     
       
         
         
             
             
         
       
     
     {3-Bromo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic acid methyl ester (Compound T22-5, 40 mg, 60.0 μmol) was dissolved in the mixture solvent of methanol (120 l) and water (30 l), added with lithium hydroxide monohydrate (10 mg, 240 μmol), and then stirred 40° C. for 15 min. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the target compound (35.2 mg, 96%). 
     LCMS: m/z 672 [M+H] +   
     HPLC retention time: 3.41 min (analysis condition D) 
     Example 678 
     Compound T22-7 
     [3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-6 (6.2 mg, 31%). 
     LCMS: m/z 518 [M+H] +   
     HPLC retention time: 1.30 min (analysis condition D) 
     Example 679 
     Compound T22-8 
     [3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic acid methyl ester 
     
       
         
         
             
             
         
       
     
     [3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic acid (Compound T22-6, 15.0 mg, 29.0 μmol) was dissolved in methanol (0.30 mL), added with trimethylsilyldiazomethane (0.10 mL), and then stirred at room temperature for 1 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the target compound (15.2 mg, 96%). 
     LCMS: m/z 532 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition D) 
     Example 680 
     Compound T23-1 
     3-Bromo-5-((R)-1,2-dihydroxyethyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound T18-1 and Compound T18-2, the title compound was prepared from Compound A5-1 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester. 
     LCMS: m/z 366 [M+H] +   
     HPLC retention time: 4.50 min (analysis condition H) 
     Example 681 
     Compound T23-2 
     3-Bromo-5-((S)-1,2-dihydroxyethyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound T18-1 and Compound T18-2, the title compound was prepared from Compound A4 and toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester. 
     LCMS: m/z 366 [M+H] +   
     HPLC retention time: 4.50 min (analysis condition H) 
     Example 682 
     Compound T24-1 
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the DMF (1 mL) suspension of 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T18-1, 112.2 mg, 0.239 mmol) and sodium hydride (60%) (19 mg, 0.477 mmol), cooled in an ice bath, methyl iodide (37 mL, 0.596 mmol) was added. The reaction mixture was stirred at room temperature for 45 min, and then added with saturated aqueous solution of ammonium chloride and saturated aqueous solution of sodium thiosulfate under ice cooling. The mixture was extracted twice with ethyl acetate/diethyl ether/hexane. The organic layer was washed with water and subsequently with aqueous solution of ammonium chloride, dried over sodium sulfate, and then concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography {Merck Kieselgel60, solution for elution:hexane/ethyl acetate (1:1)} to obtain the title compound (white solid, 107.3 mg, 93%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.41 (1H, d, 8.6 Hz), 8.35 (1H, d, 8.9 Hz), 7.56 (1H, d, 1.7 Hz), 7.46 (1H, dd, 8.6 Hz, 1.7 Hz), 7.14 (1H, d, 2.3 Hz), 7.00 (1H, dd, 8.9 Hz, 2.3 Hz), 4.60-4.49 (1H, m), 4.20-3.90 (4H, m), 4.03 (3H, s), 1.88 (6H, s), 1.50 (3H, s), 1.43 (3H, s) 
     LCMS: m/z 484 [M+H] +   
     HPLC retention time: 6.59 min (analysis condition B) 
     Example 683 
     Compound T24-2 
     3-Bromo-8-((R)-2,3-dihydroxy-propoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (0.15 mL)-MeOH (0.1 mL) solution of 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T24-1, 15.5 mg, 0.0320 mmol), 0.5 M aqueous solution of sulfuric acid (128 μL, 0.0640 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55° C. for 2 hr, cooled to room temperature, and then added with diethyl ether and subsequently with sodium hydrogen carbonate (11 mg). The mixture was extracted twice with diethyl ether/ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain the title compound (white solid, 11.9 mg, 84%). 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.26 (1H, d, 8.6 Hz), 8.20 (1H, d, 8.9 Hz), 7.77 (1H, d, 1.7 Hz), 7.42 (1H, dd, 8.6 Hz, 1.7 Hz), 7.33 (1H, d, 2.3 Hz), 7.09 (1H, dd, 8.9 Hz, 2.3 Hz), 4.26-3.96 (3H, m), 4.10 (3H, s), 3.74-3.66 (1H, m), 1.92 (6H, s) 
     LCMS: m/z 444 [M+H] +   
     HPLC retention time: 4.65 min (analysis condition B) 
     Example 684 
     Compound T25 
     3-Bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A3-1 and Compound A4, the title compound was prepared from 3,4-dihydro-1H-naphthalen-2-one (560 mg). 
     LCMS: m/z 340 [M+H] +   
     HPLC retention time: 4.57 min (analysis condition H) 
     Example 685 
     Compound T26-1 
     8-[(4R,5R)-5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-iodo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 3-bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 300 mg, 0.47 mmol), sodium iodide (147 mg, 0.94 mmol) and copper iodide (9.40 mg, 0.047 mmol) were dissolved in dioxane (1.00 ml), added with (1R,2R)—N,N,N′,N′-tetramethyl-cyclohexane-1,2-diamine (15.4 μl, 0.094 mmol), and then stirred at 110° C. for 16 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the title compound (220 mg, 70%). 
     LCMS: m/z 662 [M+H] +   
     HPLC retention time: 3.40 min (analysis condition D) 
     Example 686 
     Compound T26-2 
     3-Iodo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T26-1 (17.0 mg, 90%). 
     LCMS: m/z 508 [M+H] +   
     HPLC retention time: 1.77 min (analysis condition D) 
     Example 687 
     Compound T27-1 
     3-Bromo-9-(2-fluoro-4-methoxy-phenyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     To the mixture of 6-bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 410 mg, 1.44 mmol), tetrakistriphenylphosphine palladium (80 mg, 0.05 eq.) and sodium carbonate (614 mg, 4 eq.), toluene (3 mL) and water (1 ml) were added and then stirred at room temperature and at 90° C. for 3 hr. The mixture was extracted by adding water and diethyl ether, and the organic layer was washed with brine, and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 6-(2-fluoro-4-methoxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (white solid, 320 mg). 
     Thus-obtained 6-(2-fluoro-4-methoxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (320 mg, 0.1 mmol) and 3-bromophenylhydrazine (0.29 g, 1.3 eq.) were dissolved in acetic acid (1 mL), and stirred under nitrogen atmosphere at 90° C. for 8 hr. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, dried over magnesium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were dissolved in THF (3 mL) comprising 10% water, added with DDQ (227 mg, 3 eq.) at room temperature, and stirred at room temperature for 2 hr. To the reaction solution, the mixture solution of THF/diethyl ether (1:1) was added, and the reaction solution was washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (red solid, 75 mg). 
     LCMS: m/z 494, 496 [M+H] +   
     HPLC retention time: 3.10 min (analysis condition C) 
     Example 688 
     Compound T27-2 
     3-Bromo-9-(2-fluoro-4-hydroxy-phenyl)-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound T27-1. 
     LCMS: m/z 464, 466 [M+H] +   
     HPLC retention time: 2.68 min (analysis condition C) 
     Example 689 
     Compound U5 
     4-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     2-Bromo-3-nitro-benzonitrile (Compound U1, 678 mg, 2.987 mmol) was dissolved in ethanol (20.9 mL) and water (8.96 mL), added with acetic acid (2.39 mL, 41.81 mmol) and iron (1.17 g, 20.91 mmol), and stirred at 60° C. for 18 hr. The reaction solution was poured into aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. After concentration under reduced pressure, 3-amino-2-bromo-benzonitrile (Compound U2) was obtained as a crude product. 
     The crude product obtained from the above was dissolved in 12 M aqueous solution of hydrochloric acid (4.00 mL), added slowly at 0° C. with aqueous solution in which sodium nitrite (247 mg, 3.584 mmol) is dissolved in water (3.58 mL), and then the mixture was stirred at 0° C. for 30 min. Under light-shielding conditions, aqueous solution in which tin chloride dihydrate (2.02 g, 8.961 mmol) is dissolved in 12 M aqueous solution of hydrochloric acid (4.00 mL) was slowly added to the reaction solution at 0° C., and then the mixture was stirred at 0° C. for 1 hr. The reaction solution was poured into 5 M aqueous solution of sodium hydroxide, extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and filtered. After concentration under reduced pressure, 2-bromo-3-hydrazino-benzonitrile (Compound U3) was obtained as a crude product. Under nitrogen atmosphere, the above crude product and 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 462 mg, 2.260 mmol) were added with TFA (6.78 mL) and stirred at 100° C. for 2 hr. After cooling, the reaction solution was poured into saturated aqueous solution of sodium bicarbonate, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and filtered. After concentration under reduced pressure, 4-bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U4) was obtained as a crude product. The above crude product was dissolved in THF (10.0 mL) and water (1.00 mL), added with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.54 g, 6.780 mmol), and stirred at room temperature for 20 hr. The reaction solution was poured into 1 M aqueous solution of sodium hydroxide, extracted with cyclopentylmethyl ether, washed with 1 M aqueous solution of sodium hydroxide, water and saturated brine, dried over sodium sulfate, and filtered. The residues obtained after concentration under reduced pressure were washed with cyclopentylmethyl ether to obtain the title compound (460 mg, 52%). 
     LCMS: m/z 395 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition D) 
     Example 690 
     Compound U6 
     8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     4-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 325 mg, 0.822 mmol) was added with pyridine hydrochloride salt (3.80 g, 32.89 mmol) and stirred at 160° C. for 28 hr. The reaction solution was poured into water, extracted with ethyl acetate, washed with water, dried over sodium sulfate, and filtered. After concentration under reduced pressure, the title compound was obtained as a crude product. 
     LCMS: m/z 381 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition D) 
     Example 691 
     Compound U7-1 
     4-Bromo-8-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U6 and (R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol (354 mg, 87%). 
     LCMS: m/z 495 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition D) 
     Example 692 
     Compound U7-2 
     4-Bromo-8-((S)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U7-1. 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition C) 
     Example 693 
     Compound U8-2 
     8-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound U7-1 and Compound U7-2, the title compound was prepared from the reaction between Compound U6 and (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (4.5 mg, 29%). 
     LCMS: m/z 455 [M+H] +   
     HPLC retention time: 2.37 min (analysis condition C) 
     Example 694 
     Compound U8-3-1 
     8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,4-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U6, 20.0 mg, 40.37 μmol) was dissolved in DMA (0.35 mL), added with copper (I) cyanide (18.1 mg, 201.9 μmol), and stirred at 200° C. for 1 hr under irradiation with microwave. The reaction solution was poured into water, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product. 
     LCMS: m/z 442 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition D) 
     Example 695 
     Compound U8-3-2 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,4-dicarbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-3-1 (9.5 mg, 59%). 
     LCMS: m/z 402 [M+H] +   
     HPLC retention time: 2.40 min (analysis condition D) 
     Example 696 
     Compound U8-4-1 
     8-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound U9, the title compound was prepared as a crude product from Compound U8-1 (9.5 mg, 59%). 
     LCMS: m/z 433 [M+H] +   
     HPLC retention time: 2.34 min (analysis condition A) 
     Example 697 
     Compound U8-4-2 
     8-((R)-2,3-Dihydroxy-propoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-4-1 (crude product) (9.7 mg, 52%). 
     LCMS: m/z 393 [M+H] +   
     HPLC retention time: 1.69 min (analysis condition A) 
     Example 698 
     Compound U8-4-3 
     8-((R)-2,3-Dihydroxy-propoxy)-4-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 8-((R)-2,3-dihydroxy-propoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-4-2, 8.0 mg, 20.39 μmol) was dissolved in methanol (2.0 mL) and chloroform (2.00 mL), added with trimethylsilyldiazomethane (diethyl ether solution, 2 M, 15.3 μL, 30.58 μmol) and diisopropylethylamine (0.05 mL), and then stirred at room temperature for 31 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the title compound (5.1 mg, 62%). 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 3.74 min (analysis condition A) 
     Example 699 
     Compound U8-5-1 
     8-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-4-trifluoromethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 25.0 mg, 50.47 μmol) was dissolved in DMF (0.75 mL), added with copper iodide (I) (48.0 mg, 252.3 μmol) and difluoro-fluorosulfonyl-acetic acid methyl ester (31.9 μL, 252.3 μmol), and then stirred at 100° C. for 2 days. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product. 
     LCMS: m/z 485 [M+H] +   
     HPLC retention time: 2.88 min (analysis condition A) 
     Example 700 
     Compound U8-5-2 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-4-trifluoromethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-5-1 (4.0 mg, 30%). 
     LCMS: m/z 445 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition A) 
     Example 701 
     Compound U8-6-1 
     4-Cyclopropyl-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 2-cyclopropyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (13.2 mg, 78.73 μmol) and potassium phosphate (212.27 mg, 212.0 μmol) were dissolved in water (0.20 mL), and the mixture was stirred at room temperature for 15 min. To the reaction solution, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 μmol), palladium acetate (1.36 mg, 6.056 μmol), and tricyclohexylphosphine (toluene solution, 20 wt %, 17.0 mg, 12.11 μmol) were added and the mixture was stirred at 80° C. for 24 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (13.6 mg, 49%). 
     LCMS: m/z 457 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition D) 
     Example 702 
     Compound U8-6-2 
     4-Cyclopropyl-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-6-1. 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 2.42 min (analysis condition A) 
     Example 703 
     Compound U8-7-1 
     (S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 μmol) and lithium chloride (7.70 mg, 181.7 μmol) were dissolved in DMF (1.00 mL), added with tetramethyl tin (12.5 μL, 90.84 μmol), tetrakistriphenylphosphine palladium (3.50 mg, 6.056 μmol) and tricyclohexylphosphine (toluene solution, 20 wt %, 17.0 mg, 3.028 μmol), and the mixture was stirred at 100° C. for 24 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile as a crude product (20.9 mg, 80%). 
     Example 704 
     Compound U8-7-2 
     8-((R)-2,3-Dihydroxy-propoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-7-1. 
     LCMS: m/z 391 [M+H] +   
     HPLC retention time: 1.82 min (analysis condition A) 
     Example 705 
     Compound U8-8-1 
     3-Cyano-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 μmol), palladium acetate (1.36 mg, 6.056 μmol), 1,1′-bis(diphenylphosphino)ferrocene (3.36 mg, 6.056 μmol), imidazole (4.12 mg, 60.56 μmol) and tert-potassium butoxy (10.2 mg, 90.84 μmol) were dissolved in formamide (3.00 mL) and the mixture was stirred at 180° C. for 5 min under irradiation with microwave. The reaction solution was poured into water, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound (7.6 mg, 27%). 
     LCMS: m/z 460 [M+H] +   
     HPLC retention time: 1.82 min (analysis condition A) 
     Example 706 
     Compound U8-8-2 
     3-Cyano-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-8-1. 
     LCMS: m/z 421 [M+H] +   
     HPLC retention time: 1.57 min (analysis condition A) 
     Example 707 
     Compound U8-8-3 
     3-Cyano-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     The title compound was obtained as a by-product of the synthesis of Compound U8-8-2. 
     LCMS: m/z 420 [M+H] +   
     HPLC retention time: 1.27 min (analysis condition A) 
     Example 708 
     Compound U9 
     4-Hydroxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 10.0 mg, 25.30 μmol), X-phos (1.07 mg, 2.530 μmol), sodium hydroxide (4.36 mg, 75.90 μmol) and Pd 2 dba 3 .CHCl 3  (1.31 mg, 1.265 μmol) were dissolved in dioxane (0.50 mL) and water (0.50 mL) and the mixture was stirred at 100° C. for 1 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) and washed with dichloromethane to obtain the title compound (5.4 mg, 64%). 
     LCMS: m/z 333 [M+H] +   
     HPLC retention time: 1.62 min (analysis condition D) 
     Example 709 
     Compound U10-1 
     4-((R)-2,3-Dihydroxy-propoxy)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U9 and (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol. 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 2.06 min (analysis condition A) 
     Example 710 
     Compound U10-2 
     4-((S)-2,3-Dihydroxy-propoxy)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U9 and (R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol. 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 2.06 min (analysis condition A) 
     Example 711 
     Compound U11 
     4-Amino-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 4-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 25.0 mg, 63.25 μmol), copper iodide (2.41 mg, 12.65 μmol), sodium azide (20.6 mg, 316.3 μmol), (1S,2S)—N,N′-dimethyl-cyclohexane-1,2-diamine (2.70 mg, 18.98 μmol), and sodium ascorbate (1.25 mg, 6.325 μmol) were dissolved in ethanol (0.70 mL) and water (0.30 mL) and the mixture was stirred at 100° C. for 2 hr. The reaction solution was poured into aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the title compound (5.6 mg, 27%). 
     LCMS: m/z 332 [M+H] +   
     HPLC retention time: 2.16 min (analysis condition A) 
     Example 712 
     Compound V2 
     3-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, the acetic acid (1 mL) suspension of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 101.0 mg, 0.495 mmol) and (3-fluoro-phenyl)-hydrazine hydrochloric acid salt (Compound VI, 96.5 mg, 0.593 mmol) was stirred at ambient temperature of 95° C. for 3.75 hr. After cooling to room temperature, the reaction mixture was added with water (1 mL) and hexane/ethyl acetate (15:1) (0.5 mL), and stirred at room temperature for 15 min. The solid was filtered, washed with hexane/ethyl acetate (15:1), and then dried under reduced pressure to obtain the title compound (beige powder, 72.7 mg, 50%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.92-7.82 (1H, b), 7.47 (1H, dd, 8.9 Hz, 5.6 Hz), 7.10-7.03 (2H, m), 6.95-6.81 (2H, m), 4.05 (2H, s), 3.86 (3H, s), 1.67 (6H, s) 
     Example 713 
     Compound V3 
     3-Fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (1.8 mL)-water (0.18 mL) solution of 3-fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole (Compound V2, 72.4 mg, 0.245 mmol), DDQ (122.4 mg, 0.539 mmol) was added and the mixture was stirred at room temperature for 5 hr. The reaction mixture was added with diethyl ether and 0.5 N aqueous solution of sodium hydroxide (2 mL), and the resulting mixture was extracted twice with diethyl ether. The organic layer was washed twice with 0.5 N aqueous solution of sodium hydroxide (2 mL) and subsequently twice with brine (2 mL), and dried over sodium sulfate. After concentration under reduced pressure, hexane/ethyl acetate (5:1) and diethyl ether were added to the obtained crude product, and the solid was triturated. After removing the supernatant and drying under reduced pressure, the title compound was obtained (yellow solid, 57.0 mg, 75%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.54-8.44 (1H, b), 8.43-8.33 (2H, m), 7.16-6.98 (4H, m), 3.93 (3H, s), 1.77 (6H, s) 
     Example 714 
     Compound V4 
     3-Fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Mixture of 3-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V3, 56.6 mg, 0.183 mmol) and pyridinium chloride (0.65 g) was stirred at ambient temperature of 160° C. for 12 hr. The reaction mixture was cooled to room temperature, added with ethyl acetate and water, and the resulting mixture was extracted four times with ethyl acetate. The organic layer was washed with water three times, dried over sodium sulfate, and concentrated under reduced pressure. The obtained crude product was used for the next step without further purification (brown solid, 61.6 mg, 100%). 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.20 (1H, dd, 8.9 Hz, 5.3 Hz), 8.15 (1H, d, 9.6 Hz), 7.17 (1H, dd, 9.6 Hz, 2.3 Hz), 7.12 (1H, d, 2.3 Hz), 7.05-6.95 (1H, m), 6.88 (1H, dd, 8.9 Hz, 2.3 Hz), 1.74 (6H, s) 
     Example 715 
     Compound V5-1 
     8-[(1R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (1.5 mL) solution of 3-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V4, 0.183 mmol), (4S,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl[1,3]dioxolan-4-ol (75.9 mg, 0.275 mmol) and triphenylphosphine (72 mg, 0.275 mmol), toluene solution (125 μL, 0.275 mmol) of DEAD was added dropwise at room temperature. The reaction mixture was stirred at ambient temperature of 40° C. for 7 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, and the resulting crude product was purified by preparative TLC (Merck 60 F254, 0.5 mm) {solution for elution:hexane/ethyl acetate (3:1)} to obtain the title compound (pale orange amorphous, 54.1 mg, 53.4%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.54-8.45 (1H, b), 8.42-8.33 (2H, m), 7.17-6.99 (4H, m), 4.41-4.27 (2H, m), 4.25-4.15 (1H, m), 4.06-3.96 (1H, m), 3.96-3.88 (1H, m), 3.83-3.74 (1H, m), 1.76 (3H, s), 1.75 (3H, s), 1.48 (3H, s), 1.47 (3H, s), 0.87 (9H, s), 0.092 (6H, s) 
     Example 716 
     Compound V5-2 
     3-Fluoro-6,6-dimethyl-8-((3R,4R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (0.3 mL)-MeOH (0.1 mL) solution of 8-[(1R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V5-1, 52.8 mg, 0.0954 mmol), 0.5 M aqueous solution of sulfuric acid (0.19 mL, 0.0954 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55° C. for 4 hr, cooled to room temperature, and then added with diethyl ether, sodium hydrogen carbonate (20 mg) and water in order. The mixture was extracted twice with diethyl ether and subsequently twice with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was washed with dichloromethane, and dried under reduced pressure to obtain the title compound (white powder, 29.9 mg, 78%). 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.24 (1H, d, 8.9 Hz), 8.19 (1H, dd, 8.6 Hz, 5.3 Hz), 7.30 (1H, d, 2.3 Hz), 7.18 (1H, dd, 9.2 Hz, 2.3 Hz), 7.09 (1H, dd, 8.9 Hz, 2.3 Hz), 7.06-6.96 (1H, m), 4.32-4.22 (1H, m), 4.21-4.12 (1H, m), 4.11-4.02 (1H, m), 3.84-3.75 (1H, m), 3.74-3.61 (2H, m), 1.77 (6H, s) 
     LCMS: m/z 400 [M+H] +   
     HPLC retention time: 4.02 min (analysis condition H) 
     Example 717 
     Compound W2 
     7-((S)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     To the toluene suspension of sodium t-butoxide (700 mg, 2.5 eq.), 8-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound W1, 500 mg, 2.9 mmol) was added dropwise at 0° C. After 15 minutes, the solution turned into blackish green color. The mixture solution was added dropwise with methyl iodide (1.03 g, 2.5 eq.) and stirred at 15° C. overnight. Brown solid precipitated. The reaction solution was added to saturated aqueous solution of ammonium chloride/diethyl ether under stirring and cooling. After that, the solution was extracted with diethyl ether, and dried over sodium sulfate. After removing the solvent under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (350 mg). 
     Thus-obtained 8-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (250 mg, 1.23 mmol) and 3-cyanophenylhydrazine (0.2 g, 1.2 eq.) were dissolved in trifluoroacetic acid (1 mL), and stirred at 120° C. for 1 hr under irradiation with microwave. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, dried over magnesium sulfate, and filtered. The residues obtained after concentration under reduced pressure were dissolved in THF (3 mL) comprising 10% water and added at room temperature with DDQ (227 mg, 3 eq.). The mixture was then stirred at room temperature for 2 hr. The reaction solution was added with mixture solution of THF/diethyl ether (1:1), washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 7-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (brown solid, 54 mg). 
     LCMS: m/z 317 [M+H] +   
     HPLC retention time: 1.00 min (analysis condition I) 
     Example 718 
     Compound W3 
     7-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as Compound A6, the title compound was prepared from Compound W2. 
     LCMS: m/z 316 [M+H] +   
     HPLC retention time: 0.93 min (analysis condition I) 
     Example 719 
     Compound W4-1 
     7-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, 7-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound W3, 15 mg, 0.05 mmol) and triphenylphosphine (40 mg, 3 eq.) were added with THF (1 ml), further added dropwise with ((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (20 mg, 3 eq.) and 2.19 N toluene solution of diethyl azodicarboxylate (68 μL, 3 eq.), and the mixture was stirred at 50° C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine, dried over sodium sulfate, and filtered. The residues obtained after concentration under reduced pressure were purified by preparative TLC (ethyl acetate/dichloromethane), and the resulting solid was washed with dichloromethane to obtain the target compound (brown powder, 5 mg). 
     LCMS: m/z 417 [M+H] +   
     HPLC retention time: 1.04 min (analysis condition I) 
     Example 720 
     Compound W4-2 
     7-((S)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as Compound S7-2, the title compound was prepared from Compound W4-1. 
     LCMS: m/z 377 [M+H] +   
     HPLC retention time: 0.88 min (analysis condition I) 
     Example 721 
     Compound X1 
     1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     7-Methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 100 mg, 0.568 mmol) was dissolved in toluene (4 mL), added with NaH (60% in oil, 68 mg, 3 eq.), and stirred at room temperature for 10 min. The mixture solution was added with bis-(2-iodo-ethyl)-p-toluenesulfonamide (172 mg, 0.568 mmol), and stirred at 70° C. for 2 hr under nitrogen stream. After cooling, the reaction solution was added to saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/3:1) to obtain the title compound (colorless oily substance, 62 mg, 33%). 
     LCMS: m/z 400 [M+H] +   
     HPLC retention time: 2.02 min (analysis condition B) 
     Example 722 
     Compound X2 
     1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound X1, 400 mg, 1.0 mmol) and phenylhydrazine (217 mg, 1.5 eq.) were dissolved in acetic acid (6 mL), and the mixture was stirred at 120° C. for 4 hr under nitrogen atmosphere. After cooling, the reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/4:1) to obtain the title compound (brown solid, 185 mg, 43%). 
     LCMS: m/z 473 [M+H] +   
     HPLC retention time: 7.23 min (analysis condition B) 
     Example 723 
     Compound X3 
     6,6-Spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     6,6-Spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-5H-benzo[b]carbazole (Compound X2, 400 mg, 0.848 mmol) and DDQ (770 mg, 4 eq.) were dissolved in THF (10 mL) and water (2 mL), and then the mixture was stirred at 50° C. for 5 hr. After cooling, the reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/3:1) to give a solid, which was then washed with ethyl ether to obtain the title compound (yellow solid, 86 mg, 21%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 11.9 (1H, s), 8.22 (2H, m), 7.75 (2H, d), 7.60 (4H, m) 7.30 (2H, m), 7.11 (1H, d), 3.81 (2H, m), 3.68 (3H, s), 3.62 (2H, m), 2.49 (3H, s), 2.21 (2H, m), 2.10 (2H, m), 
     LCMS: m/z 487 [M+H] +   
     HPLC retention time: 6.05 min (analysis condition B) 
     Example 724 
     Compound X4 
     6,6-Spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Mixture of 6,6-spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-benzo[b]carbazol-11-one (Compound X3, 35 mg, 0.072 mmol) and pyridine hydrochloride salt (800 mg) was stirred in a sealing tube at 160° C. for 10 hr. After cooling, the reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane:methanol/4:1) to obtain the title compound (yellow solid, 30 mg, 98%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 8.20 (1H, m), 8.10 (1H, m), 7.53 (1H, m), 7.25 (3H, m), 6.80 (1H, m), 3.60 (2H, m), 3.45 (2H, m), 2.52 (2H, m), 2.05 (2H, m). 
     LCMS: m/z 319 [M+H] +   
     HPLC retention time: 2.86 min (analysis condition B) 
     Example 725 
     Compound X5 
     8-(2-Diethylaminoethoxy)-6,6-spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     6,6-Spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one (Compound X4, 30 mg, 0.094 mmol), diethylaminoethanol (22 mg, 2 eq.), triphenylphosphine (50 mg, 2 eq.) and DIAD (39 mg, 2 eq.) were dissolved in THF (4 mL) and the mixture was stirred at room temperature for 4 hr. The reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane:methanol/4:1) to obtain the title compound (yellow oily substance, 6.8 mg, 17%). 
     LCMS: m/z 418 [M+H] +   
     HPLC retention time: 2.75 min (analysis condition B) 
     Example 726 
     Compound Y2 
     2,3-Dichloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, the acetic acid (1 mL) suspension of 7-methoxy-1,1-dimethyl-3,4-dihydro-TH-naphthalen-2-one (Compound A2, 92.3 mg, 0.452 mmol) and (3,4-dichlorophenyl)hydrazine hydrochloric acid salt (Compound Y1, 96.5 mg, 0.452 mmol) was stirred at ambient temperature of 90° C. for 3.5 hr. After cooling to room temperature, the reaction mixture was added with diethyl ether and water, and the resulting mixture was extracted twice with diethyl ether. The organic layer was washed three times with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography {Merck Kieselgel60, solution for elution:hexane/ethyl acetate (4:1)} to obtain the title compound (pale yellow solid, 62.1 mg, 40%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.92-7.84 (1H, b), 7.62 (1H, s), 7.46 (1H, s), 7.05 (1H, d, 2.6), 6.84 (1H, dd, 8.6 Hz, 2.6 Hz), 4.01 (2H, s), 3.86 (3H, s), 1.67 (6H, s) 
     Example 727 
     Compound Y3 
     2,3-Dichloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the 1,4-dioxane (1.7 mL)-water (0.1 mL) solution of 2,3-dichloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole (Compound Y2, 61.0 mg, 0.176 mmol), DDQ (120 mg, 0.529 mmol) was added and the mixture was stirred at room temperature for 16 hr and 15 min. The reaction mixture was purified by flash column chromatography {Merck Kieselgel60, solution for elution:hexane/ethyl acetate (2:1)} to obtain the title compound (pale orange solid, 16.7 mg, 26%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.55 (1H, s), 8.42-8.36 (1H, b), 8.39 (1H, d, 8.6 Hz), 7.54 (1H, s), 7.08 (1H, d, 2.3 Hz), 7.03 (1H, dd, 8.6 Hz, 2.3 Hz), 3.93 (3H, s), 1.76 (6H, s) 
     Example 728 
     Compound Y4 
     2,3-Dichloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Mixture of 2,3-dichloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y3, 16.5 mg, 0.0457 mmol) and pyridinium chloride (0.2 g) was stirred at ambient temperature of 160° C. for 7 hr. The reaction mixture was cooled to room temperature and added with ethyl acetate and water. The mixture was extracted three times with ethyl acetate. The organic layer was washed twice with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was used for the next step without further purification (brown solid, 14.8 mg, 94%). 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.34 (1H, s), 8.14 (1H, d, 8.6 Hz), 7.61 (1H, s), 7.10 (1H, d, 2.3 Hz), 6.89 (1H, dd, 8.6 Hz, 2.3 Hz), 1.75 (1H, s) 
     Example 729 
     Compound Y5-1 
     8-[(1R,5R)-5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-2,3-dichloro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (0.3 mL) solution of 2,3-dichloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y4, 12.9 mg, 0.0373 mmol), (4S,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-ol (15.5 mg, 0.0559 mmol) and triphenylphosphine (14.7 mg, 0.0559 mmol), toluene solution (25.4 μL, 0.0559 mmol) of DEAD was added dropwise at room temperature. The reaction mixture was stirred at ambient temperature of 40° C. for 4 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, and the resulting crude product was purified by preparative TLC (Merck 60 F254, 0.5 mm) {solution for elution:hexane/ethyl acetate (3:1)} to obtain the title compound (white solid, 15.1 mg, 67%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 8.55 (1H, s), 8.44-8.37 (1H, b), 8.37 (1H, d, 8.6 Hz), 7.54 (1H, s), 7.15 (1H, d, 2.6 Hz), 7.03 (1H, dd, 8.6 Hz, 2.6 Hz), 4.41-4.26 (2H, m), 4.25-4.15 (1H, m), 4.06-3.86 (2H, m), 3.83-3.73 (1H, m), 1.76 (3H, s), 1.75 (3H, s), 1.48 (3H, s), 1.47 (3H, s), 0.90 (9H, s), 0.092 (6H, s) 
     Example 730 
     Compound Y5-2 
     2,3-Dichloro-6,6-dimethyl-8-((3R,4R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     Under nitrogen atmosphere, to the THF (0.2 mL)-MeOH (0.1 mL) solution of 8-[(1R,5R)-5-(tert-butyldimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-2,3-dichloro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y5-1, 14.6 mg, 0.0242 mmol), 0.5 M aqueous solution of sulfuric acid (96.6 μL, 0.0483 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55° C. for 3 hr, cooled to room temperature, and then added with diethyl ether and sodium hydrogen carbonate (10 mg) in order. The mixture was extracted twice with diethyl ether, and the organic layer was washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was washed with dichloromethane, and dried under reduced pressure to obtain the title compound (white solid, 8.3 mg, 76%). 
       1 H-NMR (270 MHz, CD 3 OD) δ: 8.35 (1H, s), 8.24 (1H, d, 8.9 Hz), 7.62 (1H, s), 7.31 (1H, d, 2.3 Hz), 7.10 (1H, dd, 8.9 Hz, 2.3 Hz), 4.31-4.23 (1H, m), 4.12-4.12 (1H, m), 4.11-4.02 (1H, m), 3.84-3.74 (1H, m), 3.73-3.61 (1H, m), 1.78 (6H, s) 
     LCMS: m/z 450 [M+H] +   
     HPLC retention time: 4.92 min (analysis condition H) 
     Example 731 
     Compound Z3 
     2-[1-(2-Bromo-5-methoxy-phenyl)-1-methylethyl]-benzo[b]thiophene 
     
       
         
         
             
             
         
       
     
     2-(2-Bromo-5-methoxyphenyl)-2-methyl-propionic acid (1.5 g, 5.5 mmol) was dissolved in methylene chloride (15 mL), added with oxalyl chloride (1.5 mL) and dimethylformamide (2 micro liter) at room temperature, and the mixture was stirred at room temperature for 30 min. After removing the solvent, the residues were dissolved in toluene, added at room temperature with 2-[(triphenyl-5-phosphanyl)-methyl]-benzenethiol hydrobromide (2.56 g, 5.5 mmol) and triethylamine (2.27 mL), and then the mixture was refluxed under heating for 30 min. Thereafter, the mixture was cooled to 0° C., added with lithium hexamethyldisilazide (1 M tetrahydrofuran solution, 5.5 mL), and refluxed under heating for 24 hr. The reaction mixture was extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (0.55 g, 28%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 6.61 (1H, s), 3.37 (3H, s), 1.83 (6H, s) 
     Example 732 
     Compound Z4 
     2-(1-Benzo[b]thiophen-2-yl-1-methyl-ethyl)-4-methoxy-benzoic acid 
     
       
         
         
             
             
         
       
     
     2-[1-(2-Bromo-5-methoxy-phenyl)-1-methylethyl]-benzo[b]thiophene (Compound Z3, 40 mg, 0.11 mmol) was dissolved in tetrahydrofuran (0.5 mL), cooled to −78° C., added with n-butyl lithium (1.57 M, hexane solution, 0.07 mL), and the mixture was stirred for 10 min. The reaction mixture was added with dry ice and then maintained for 1 hr. After that, the mixture was added with 0.5 N hydrochloric acid, extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (22 mg, 55%). 
       1 H-NMR (270 MHz, CDCl 3 ) δ: 7.46 (1H, d), 7.44 (1H, d), 6.92 (s, 1H), 6.70 (d, 1H), 3.84 (s, 3H), 1.89 (6H, s) 
     Example 733 
     Compound Z5 
     8-Methoxy-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one 
     
       
         
         
             
             
         
       
     
     To 2-(1-benzo[b]thiophen-2-yl-1-methylethyl)-4-methoxy-benzoic acid (Compound Z4, 68 mg, 0.22 mmol), polyphosphoric acid (3.5 g) was added, and the mixture was stirred for 1 hr at 100° C. under heating. The mixture was added with water, extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (41 mg, 63%). 
     LCMS: m/z 309 [M+H] +   
     HPLC retention time: 2.89 min (analysis condition C) 
     Example 734 
     Compound Z6 
     8-Hydroxy-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as Compound A6, the title compound was prepared from Compound Z5. 
     LCMS: m/z 295 [M+H] +   
     HPLC retention time: 2.91 min (analysis condition F) 
     Example 735 
     Compound Z7 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one 
     
       
         
         
             
             
         
       
     
     According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound Z6. 
     LCMS: m/z 394 [M+H] +   
     HPLC retention time: 5.06 min (analysis condition F) 
     Example 736 
     Compound Z9 
     2-Bromo-1,3-dihydroxytetrahydropyranbenzene 
     
       
         
         
             
             
         
       
     
     To 4-bromo-benzene-1,3-diol (Compound Z8, 20 g, 105.8 mmol) and 3,4-dihydro-2H-pyran (38.6 mL), pyridium paratoluenesulfonate (266 mg) was added, and the mixture was stirred at 50° C. for 1 hr. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (31.82 mg, 84%). 
     LCMS: m/z 358 [M+H] +   
     HPLC retention time: 3.15 min (analysis condition C) 
     Example 737 
     Compound Z10 
     3-(2,4-Dihydroxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 10 g), 2-bromo-1,3-dihydroxytetrahydropyranbenzene (Compound Z9, 20.98 g), sodium t-butoxide (5.88 g), palladium acetate (550 mg) and tri-t-butylphosphonium tetrafluoroborate (710 mg), toluene (40 mL) was added and the mixture was stirred and heated at 70° C. under nitrogen atmosphere for 6 hr. After cooling, the reaction mixture was added with methanol (38 mL) and trifluoroacetic acid (14.54 mL) at room temperature, and then stirred at room temperature overnight. To the resulting residues, methylene chloride and saturated dipotassium hydrogen phosphate were added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (5.53 g, 36%). 
     LCMS: m/z 312 [M+H] +   
     HPLC retention time: 2.39 min (analysis condition F) 
     Example 738 
     Compound Z11 
     Trifluoromethanesulfonic acid 8-methoxy-6,6-dimethyl-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester 
     
       
         
         
             
             
         
       
     
     3-(2,4-Dihydroxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-TH-naphthalen-2-one (Compound Z10, 5.53 g) was dissolved in methylene chloride (40 mL), and added with trifluoromethanesulfonic anhydride (2.98 mL) at room temperature. After cooling to 5° C., diisopropylethylamine (9.25 mL) and trifluoromethanesulfonic anhydride (4.47 mL) were added thereto. To the reaction mixture, methylene chloride and saturated dipotassium hydrogen phosphate were added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (4.82 g, 64%). 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 8.95 min (analysis condition H) 
     Example 739 
     Compound Z12 
     Trifluoromethanesulfonic acid 8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester 
     
       
         
         
             
             
         
       
     
     Trifluoromethanesulfonic acid 8-methoxy-6,6-dimethyl-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester (Compound Z11, 4.82 g) was dissolved in acetonitrile (48 mL) and water (24 mL), added with sodium chlorite (2.55 g) and N-hydroxyphthalimide (369 mg), and then the mixture was stirred at 40° C. for 1 hr. The reaction mixture was added with methylene chloride and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (2.80 g, 56%). 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 8.02 min (analysis condition H) 
     Example 740 
     Compound Z13 
     Trifluoromethanesulfonic acid 8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as Compound A6, the title compound was prepared as a crude product from Compound Z12. 
     Example 741 
     Compound Z14 
     Trifluoro-methanesulfonic acid 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6 dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was obtained as a crude product from Compound Z13 and [5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (Compound T22-0). 
     Example 742 
     Compound Z15 
     8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furane-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Trifluoro-methanesulfonic acid 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6 dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester (Compound Z14, 24 mg) was dissolved in DMF (0.5 mL), added with zinc (II) cyanide (8.2 mg) and palladium tetrakistriphenylphosphine (2.0 mg), and the mixture was stirred under heating at 200° C. for 20 min with microwave irradiation. To the reaction mixture, ethyl acetate was added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (15 mg). 
     LCMS: m/z 562 [M+H] +   
     HPLC retention time: 4.14 min (analysis condition F) 
     Example 743 
     Compound Z16 
     6,6-Dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]naphth[2,3-d]furane-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as Compound S7-2, the title compound was prepared from Compound Z15. 
     LCMS: m/z 408 [M+H] +   
     HPLC retention time: 4.51 min (analysis condition H) 
     Example 744 
     Compound K7-5 
     4-(3-Cyano-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound K6 and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester. 
     LCMS: m/z 498 [M+H] +   
     HPLC retention time: 4.24 min (analysis condition W) 
     Example 745 
     Compound K7-6 
     9-Methoxy-6,6-dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from K7-5. 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition W) 
     Example 746 
     Compound K8-1 
     8-(1-Cyclobutyl-1,2,3,6-tetrahydro-pyridin-4-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound K7-6 and cyclobutanone. 
     LCMS: m/z 452 [M+H] +   
     HPLC retention time: 2.72 min (analysis condition W) 
     Example 747 
     Compound K8-2 
     8-(1-Cyclobutyl-piperidin-4-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound K8-1. 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 2.76 min (analysis condition W) 
     Example 748 
     Compound K9-5 
     8-(1-Cyclobutyl-piperidin-4-yl)-9-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K8-2. 
     LCMS: m/z 440 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition W) 
     Example 749 
     Compound K10-8 
     8-(1-Cyclobutyl-piperidin-4-yl)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-5 and isopropyl iodide. 
     LCMS: m/z 482 [M+H] +   
     HPLC retention time: 1.74 min (analysis condition S) 
     The compounds described in the following Tables 2-3 were synthesized from the intermediates of Compound K or Compound L by alkylation of hydroxyl group according to Mitsunobu reaction used for preparing Compound A7-1 or the method used for the synthesis of Compound A7-17 (described in the Table). 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Ex- 
                   
                   
                   
                   
                   
                   
                   
               
               
                 am 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                 Meth- 
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 od 
               
               
                   
               
             
            
               
                 750 
                 K10-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-9-(tetrahydro- pyran-4-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.85  
                 555 
                 A7-1 
               
               
                   
               
               
                 751 
                 K10-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(2-Methoxy- ethoxy)-5-(2- methoxy-ethyl)- 6,6-dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.50 
                 587 
                 A7-17 
               
               
                   
               
               
                 752 
                 K10-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(2-Methoxy- ethoxy)-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.37 
                 529 
                 A7-17 
               
               
                   
               
               
                 753 
                 K10-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethoxy-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.95 
                 499 
                 A7-17 
               
               
                   
               
               
                 754 
                 K10-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-9-(tetrahydro- furan-3-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.40 
                 541 
                 A7-1 
               
               
                   
               
               
                 755 
                 K10-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-(2-Diethylamino- ethoxy)-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.13 
                 570 
                 A7-17 
               
               
                   
               
               
                 756 
                 K10-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)-9- (2-methoxy- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.45 
                 499 
                 A7-17 
               
               
                   
               
               
                 757 
                 K10-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)- 5,6,6-trimethyl-11- oxo-9-(tetrahydro- furan-3-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile  
                 S 
                 1.98 
                 525 
                 A7-1 
               
               
                   
               
               
                 758 
                 K10-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)-9- (1-ethyl-propoxy)- 5,6,6-trimethyl-11- oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile 
                 S 
                 2.43 
                 525 
                 A7-1 
               
               
                   
               
               
                 759 
                 K10-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-9- (tetrahydro-furan- 3-yloxy)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.92 
                 511 
                 A7-1 
               
               
                   
               
               
                 760 
                 K10-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-9- (tetrahydro-pyran- 4-yloxy)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile  
                 U 
                 1.97 
                 525 
                 A7-1 
               
               
                   
               
               
                 761 
                 K10-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazin-1-yl)-9- (1-ethyl-propoxy)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.82 
                 511 
                 A7-1 
               
               
                   
               
               
                 762 
                 L10-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-8-(2- methoxy-ethoxy)- 5-(2-methoxy- ethyl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 2.68 
                 477 
                 A7-17 
               
               
                   
               
               
                 763 
                 L10-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-8-(2- methoxy-ethoxy)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile  
                 S 
                 2.68 
                 419 
                 A7-17 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 764 
                 L10-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(1-Cyclobutyl- piperidin-4- ylmethoxy)-9- isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.65 
                 512 
                 A7-1  
               
               
                   
               
               
                 765 
                 L10-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-8-(1- isopropyl-piperidin- 4-ylmethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.62 
                 500 
                 A7-1  
               
               
                   
               
               
                 766 
                 L10-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(1-Cyclobutyl- piperidin-3-yloxy)- 9-isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.65 
                 498 
                 A7-1  
               
               
                   
               
               
                 767 
                 L10-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-8-(1- isopropyl-piperidin- 3-yloxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.59 
                 486 
                 A7-1  
               
               
                   
               
               
                 768 
                 L10-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-9- isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.07 
                 460 
                 A7-17 
               
               
                   
               
               
                 769 
                 L10-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-6,6- dimethyl-11-oxo-8- (pyridin-4-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.07 
                 438 
                 A7-17 
               
               
                   
               
               
                 770 
                 L10-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-6,6- dimethyl-11-oxo-8- vinyloxy-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.77 
                 387 
                 A7-17 
               
               
                   
               
               
                 771 
                 L10-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Isopropoxy-6,6- dimethyl-11-oxo-8- (tetrahydro-furan- 3-yloxy)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile  
                 S 
                 2.45 
                 431 
                 A7-1  
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 4 were synthesized from the intermediates of Compound B according to the method described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 772 
                 B3-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((3R,5S)-4- Cyclobutyl-3,5- dimethyl-piperazin-1- yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 1.90 
                 453 
                 B3-32 
               
               
                   
               
               
                 773 
                 B3-40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((3R,5S)-4-Ethyl- 3,5-dimethyl-piperazin- 1-yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 1.82 
                 427 
                 B3-32 
               
               
                   
               
               
                 774 
                 B2-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-[4-(1- methyl-piperidin-4-yl)- piperazin-1-yl]-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 1.58 
                 468 
                 B2-1  
               
               
                   
               
               
                 775 
                 B3-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclobutanecarbonyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.35 
                 453 
                 A9-10 
               
               
                   
               
               
                 776 
                 B3-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropanecarbonyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.22 
                 439 
                 A9-10 
               
               
                   
               
            
           
         
       
     
     Example 777 
     Compound E6-4 
     9-Ethyl-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound E5-1. 
     LCMS: m/z 331 [M+H] +   
     HPLC retention time: 3.42 min (analysis condition W) 
     Example 778 
     Compound E7 
     Trifluoro-methanesulfonic acid 3-cyano-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound E6-4. 
     LCMS: m/z 463 [M+H] +   
     HPLC retention time: 4.39 min (analysis condition W) 
     Example 779 
     Compound E8-1 
     9-Ethyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from Compound E7 and piperazine in the same manner as the method for synthesizing Compound B2-1. 
     LCMS: m/z 399 [M+H] +   
     HPLC retention time: 1.88 min (analysis condition U) 
     Example 780 
     Compound E8-2 
     9-Ethyl-6,6-dimethyl-8-((S)-3-methyl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound E7 and 2-(S)-methylpiperazine. 
     LCMS: m/z 413 [M+H] +   
     HPLC retention time: 2.76 min (analysis condition W) 
     Example 781 
     Compound E8-3 
     8-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound E7 and cis-2,6-dimethylpiperazine. 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 2.00 min (analysis condition U) 
     Example 782 
     Compound E8-4 
     8-(1-Cyclobutyl-1,2,3,6-tetrahydro-pyridin-4-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     Compound 7 was converted in the same manner as Compound B2-22-1 and Compound 2, and subsequently subjected to reductive amination in the same manner as Compound B3-32 to obtain the title compound. 
     
       
         
         
             
             
         
       
     
     LCMS: m/z 450 [M+H] +   
     HPLC retention time: 2.12 min (analysis condition U) 
     Example 783 
     Compound E9-1 
     8-((S)-4-Cyclobutyl-3-methyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E8-2 and cyclobutanone. 
     LCMS: m/z 467 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition W) 
     The compounds described in the following Table 5 were prepared by acylation from Compound E8-1 in the same manner as the method for synthesizing Compound A9-10. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                   
                   
                   
                   
                   
                 Reten- 
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 tion 
                 m/z 
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                   
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 784 
                 E9-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.58 
                 467 
               
               
                   
               
               
                 785 
                 E9-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclobutanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.74 
                 481 
               
               
                   
               
               
                 786 
                 E9-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4-(2- Dimethylamino-acetyl)- piperazin-1-yl]-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 1.98 
                 484 
               
               
                   
               
               
                 787 
                 E9-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4-isobutyryl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.67 
                 469 
               
               
                   
               
               
                 788 
                 E9-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Acetyl-piperazin- 1-yl)-9-ethyl-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.35 
                 441 
               
               
                   
               
               
                 789 
                 E9-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopentanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 S 
                 2.87 
                 495 
               
               
                   
               
               
                 790 
                 E9-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclohexanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 S 
                 2.97 
                 509 
               
               
                   
               
            
           
         
       
     
     Example 791 
     Compound E9-9 
     8-[4-(1-Cyano-cyclohexyl)-piperazin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Ethyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (45 mg) and cyclohexanone (25 mg) were suspended in chloroform (2 ml), added with trimethylsilyl cyanide (30 mg) and zinc iodide (5 mg), and the mixture was stirred at 60° C. for 17 hrs. The reaction mixture was diluted with ethyl acetate (20 ml) and the organic layer was washed with 1000 brine solution and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol (=99/1)) to obtain the title compound (12 mg, yield 30%). 
     LCMS: m/z 506 [M+H] +   
     HPLC retention time: 3.00 min (analysis condition U) 
     The compounds described in the following Table 6 were synthesized from Compound E8-1 or Compound PR10-1 in the same manner as the method for Compound E9-9. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 792 
                 E9-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4-(1-Cyano- cyclobutyl)-piperazin- 1-yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.88 
                 478 
               
               
                   
               
               
                 793 
                 PR11-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyano-4- hydroxy-piperazin-1- yl)-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 3.05 
                 439 
               
               
                   
               
               
                 794 
                 PR11-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyano-4- morpholine-4-yl- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile 
                 Y 
                 3.35 
                 508 
               
               
                   
               
            
           
         
       
     
     With respect to the compounds described in the following Table 7, Compound F2 was subjected to amination in the same manner as Compound B2-1. Subsequently, the preparation was carried out by reductive amination in the same manner as the method for Compound B3-32. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 795 
                 F3-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Bromo-8-((3R,5S)- 3,5-dimethyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile  
                 U 
                 2.05 
                  477, 479 
                 B2-1  
               
               
                   
               
               
                 796 
                 F4-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Bromo-8-((3R,5S)- 4-cyclobutyl-3,5- dimethyl-piperazin-1- yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 2.28 
                  531, 533 
                 B3-32 
               
               
                   
               
            
           
         
       
     
     Example 797 
     Compound PR1 
     2-(4-Vinylphenyl)-2-methylpropanoic acid 
     
       
         
         
             
             
         
       
     
     2-(4-Bromophenyl)-2-methylpropanoic acid (30 g), PPh 3  (5.0 g), potassium vinyltrifluoroborate (24.8 g), potassium carbonate (51.2 g), and palladium acetate (1.43 g) were dissolved in 1-propanol (198 ml) and distilled water (99 ml). After deaeration, the mixture was stirred under reflux for 6 hrs under nitrogen atmosphere. Insoluble matters were removed by filtration and washed with 1-propanol (210 ml). The filtrate was then concentrated under reduced pressure. Concentrated residues were partitioned between CPME (300 ml) and distilled water (150 ml, comprising 4.17 ml of ethylenediamine). The organic layer was removed and the aqueous layer was adjusted to pH 5 by using 2 N hydrochloric acid. The aqueous layer was extracted with a mixture of isopropyl acetate (240 ml) and heptane (240 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Ethanol (300 ml) was added thereto for suspending and washing the resultant. The solid was removed by Celite filtration, and the filtrate was concentrated under reduced pressure to obtain the title compound (21.7 g, 93%). 
       1 H-NMR (400 MHz CDCl 3 ) δ ppm 7.49-7.34 (4H, m), 6.69 (1H, dd, J=17.6, 11.0 Hz), 5.72 (1H, d, J=17.6 Hz), 5.23 (1H, d, 11.0 Hz), 1.59 (s, 6H) 
     HPLC retention time: 2.05 min (analysis condition S) 
     Example 798 
     Compound PR2 
     2-(4-Ethylphenyl)-2-methylpropanoic acid 
     
       
         
         
             
             
         
       
     
     2-(4-Vinylphenyl)-2-methylpropanoic acid (58 g) was dissolved in ethanol, and then stirred for 3 hrs under atmospheric hydrogen pressure in the presence of 10% palladium carbon (5.8 g). The catalyst was removed by filtration, and the filtrate was concentrated to obtain a crude product, which was then suspended and washed with hexane to give the title compound (56.5 g, 94.8%). 
       1 H-NMR (270 MHz DMSO-d 6 ) δ ppm 12.28 (1H, s), 7.27-7.22 (2H, m), 7.18-7.14 (2H, m), 2.56 (2H, q, J=7.6 Hz), 1.45 (6H, s), 1.16 (3H, t, J=7.6 Hz) 
     LCMS: m/z 193 [M+H] +   
     HPLC retention time: 2.18 min (analysis condition S) 
     Example 799 
     Compound PR3 
     2-(4-Ethyl-3-iodophenyl)-2-methylpropanoic acid 
     
       
         
         
             
             
         
       
     
     2-(4-Ethylphenyl)-2-methylpropanoic acid (58.1 g, 302.2 mmol) was dissolved in acetic acid (175 ml), added with N-iodosuccinimide (71.4 g, 317.3 mmol, 1.05 eq.) and conc. sulfuric acid (75 ml) at 0° C. Thereafter, the mixture was stirred at room temperature for 2 hrs. After cooling the reaction solution to 0° C., 10% aqueous solution of sodium hydrogen sulfite (100 ml) was added and the mixture was stirred for 1 hr. H 2 O (450 ml) was added to the mixture and the precipitated solid was filtered to obtain the title compound as a crude product. Ethanol (150 ml) and 10% aqueous solution of sodium hydrogen sulfite (50 ml) were added to the crude product, and the mixture was dissolved under heating at 50° C. After confirming the dissolution, the solution was cooled to room temperature, added with H 2 O (300 ml), and then stirred at 0° C. for 1 hr. The precipitated solid was filtered to obtain the title compound (95.8 g, 99%). 
       1 H-NMR (270 MHz DMSO-d 6 ) δ ppm 12.46 (1H, s), 7.70 (1H, d, J=1.8 Hz), 7.32 (1H, dd, J=8.1, 1.8 Hz), 7.26 (1H, d, J=8.1 Hz), 2.64 (2H, q, J=7.5 Hz), 1.43 (6H, s), 1.12 (3H, t, J=7.5 Hz) 
     HPLC retention time: 2.53 min (analysis condition S) 
     Example 800 
     Compound PR4 
     Tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoic acid 
     
       
         
         
             
             
         
       
     
     Mono-tert-butyl malonic acid (72.5 g) was dissolved in DME (360 ml), added with TEA (189 ml) and magnesium chloride (29.63 g) and the mixture was stirred for 2 hrs. In a separate vessel, CDI (52.75 g) was added to the DME (360 ml) solution of 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid (90 g) and stirred at room temperature for 1 hr to prepare a solution. This solution was then added dropwise to the aforementioned mixture, and the resulting solution was washed with DME (90 ml) and stirred at 70° C. for 3 hrs. The reaction mixture was diluted with isopropyl acetate (225 ml) and heptane (225 ml), and the organic layer was washed with 2 N hydrochloric acid (684 ml), 0.17 N hydrochloric acid (540 ml), 15% aqueous solution of ammonium chloride (540 ml), 1 N aqueous solution of sodium hydroxide (540 ml) and 15% brine (540 ml) in order. The organic layer was concentrated under reduced pressure to obtain the title compound as a crude product, which was used for the next step without further purification. 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 7.64 (1H, d, J=2.0 Hz), 7.30 (1H, d, J=8.1 Hz), 7.24 (1H, d, J=8.0, 2.0 Hz), 3.32 (2H, s), 2.65 (2H, q, J=7.4 Hz), 1.40 (6H, s), 1.34 (9H, s), 1.13 (3H, t, J=7.4 Hz) 
     Example 801 
     Compound PR5-1 
     Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     4-(4-Ethyl-3-iodophenyl)-4-methyl-3-oxopentanoic acid tert-butyl (117.76 g) was dissolved in DMF (471 ml) and added with cesium carbonate (276.5 g). DMF solution (176.6 ml) of 4-chloro-3-nitrobenzonitrile (63.9 g) was added dropwise thereto (washed with DMF 58.8 ml), and the mixture was stirred at 35° C. for 6 hrs. To the mixture, THF (588.8 ml), ethyl acetate (588.8 ml), acetic acid (72.87 ml) and distilled water (588.8 ml) were added for distribution, and the aqueous layer was removed. The organic layer was added with THF (588.8 ml) and water (588.8 ml), and under stirring sodium hydrosulfite (80%, 147.76 g) was added in small portions and the mixture was stirred at room temperature for 3 hrs. After removing the aqueous layer, the organic layer was washed with 15% brine (588.8 ml). The organic layer was added with 1 N hydrochloric acid (94.2 ml), stirred for 1 hr, and then added with 1 N aqueous solution of sodium hydroxide (329.7 ml). The aqueous layer was removed and the organic layer was concentrated under reduced pressure. The concentrated residues were dissolved in ethanol (824.3 ml) and added dropwise with distilled water (247.3 ml). The resulting precipitated crystals were filtered and collected, washed with water:ethanol (=1:2 mixture solution, 588.8 ml), and then dried to obtain the title compound (98.12 g, two-step 63.5%). 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 12.04 (1H, br. s), 8.01 (1H, d, J=8.4 Hz), 7.91 (1H, d, J=0.8 Hz), 7.55 (1H, d, J=1.8 Hz), 7.49 (1H, dd, J=1.5, 8.4 Hz), 7.16 (1H, d, J=8.1 Hz), 7.07 (1H, dd, J=2.0, 8.1 Hz), 2.58 (2H, q, J=7.4 Hz), 1.79 (6H, s), 1.23 (9H, s), 1.06 (3H, t, J=7.4 Hz) 
     LCMS: m/z 459, 515 [M+H] +   
     Example 802 
     Compound PR5-2 
     Methyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from monomethyl malonate and 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid in the same manner as the method for Compound PR4 and Compound PR5-1. 
       1 H-NMR (270 MHz DMSO-D6) δ: 12.20 (s, 1H), 8.06-8.03 (m, 1H), 7.95-7.94 (m, 1H), 7.58-7.57 (m, 1H), 7.53-7.49 (m, 1H), 7.17-7.14 (m, 1H), 7.06-7.02 (m, 1H), 3.46 (s, 3H), 2.65-2.56 (q, 2H, J=7.5 Hz), 1.78 (s, 6H), 1.12-1.07 (t, 3H, J=7.5 Hz) 
     LCMS: m/z 473 [M+H] +   
     Example 803 
     Compound PR6 
     Tert-butyl 6-cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid hydrochloric acid salt 
     
       
         
         
             
             
         
       
     
     Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid (390.5 g), 4-morpholin-4-yl piperidine (158 g), and 1,3-bis-(2,6-diisopropylphenyl)-imidazoyl-2-ylidene (allyl) palladium (II) chloride (8.83 g) were dissolved in a mixture of NaHMDS (1.9 M, THF solution 1.32 L) and DME (1.95 L) under nitrogen stream, and the mixture was stirred at 40° C. for 1 hr. The reaction mixture was then partitioned between isopropyl acetate (1.95 L) and 20% aqueous solution of ammonium chloride (1.95 L). The organic layer was washed twice with 10% brine (1.56 L), and then concentrated under reduced pressure. The resulting residues were dissolved in a mixture of DME (3.9 L) and water (78.1 ml), added with N-acetylcysteine (12.39 g), and stirred at 45° C. for 1 hr. After that, the insoluble matters were filtered and washed with DME (1.95 L). The filtrate was concentrated under reduced pressure. The resulting residues were dissolved in acetone (5.5 L) and added with the solution in which pyridinium chloride (96.5 g) is dissolved in acetone (195 ml) and ethanol (78 ml). The precipitated solid was filtered, collected, washed with acetone (1.95 L) and dried to obtain the title compound (373 g, 83%). 
       1 H-NMR (400 MHz DMSO-D 6 ) δ: 12.03 (1H, s), 10.75-10.88 (1H, m), 7.99 (1H, d, J=8.3 Hz), 7.93 (1H, d, J=1.3 Hz), 7.46 (1H, dd, J=1.3, 8.1 Hz), 7.10 (1H, d, J=7.9 Hz), 6.88 (1H, dd, J=1.7, 7.9 Hz), 6.79 (1H, d, J=1.7 Hz), 3.91-4.01 (2H, m), 3.76-3.87 (2H, m), 3.37-3.46 (2H, m), 3.22 (1H, m), 2.94-3.11 (4H, m), 2.57 (2H, q, J=7.5 Hz), 2.45-2.53 (2H, m), 2.09-2.16 (2H, m), 1.80 (6H, s), 1.71-1.77 (2H, m), 1.19 (9H, s), 1.14 (3H, t, J=7.5 Hz) 
     LCMS: m/z 557 [M+H] +   
     Example 804 
     Compound PR7 
     6-Cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     Tert-butyl 6-cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid hydrochloric acid salt (1400 g) was suspended in TFE (7 L) under nitrogen stream, and added dropwise with TMSCl (554 ml) at 8° C. After stirring for 3 hrs, the reaction solution was added with acetone (5.6 L) and aqueous solution of NaOH (1 N, 4.39 L), and 10% aqueous solution of K 2 HPO 4  (1.4 L) was added thereto for neutralization. The precipitated solid was filtered and collected, washed twice with a mixture solution of water:acetone (=1:1, 2.8 L), and dried to obtain the title compound (1061 g, 96.6%). 
       1 H-NMR (270 MHz DMSO-D 6 ) δ: 11.95 (1H, s), 11.92 (1H, bs), 8.04 (1H, d, J=8.4 Hz), 7.89 (1H, d, J=1.3 Hz), 7.44 (1H, J=dd, 1.3, 8.4 Hz), 7.00 (1H, d, J=8.4 Hz), 6.88 (1H, d, J=1.8 Hz), 6.71 (1H, dd, J=2.2, 7.9 Hz), 3.50-3.55 (4H, m), 2.92-2.96 (2H, m), 2.54 (2H, q, 7.5 Hz), 2.39-2.50 (6H, m), 2.15-2.22 (1H, m), 1.74-1.85 (8H, m), 1.43-1.52 (2H, m), 1.13 (3H, t, J=7.5 Hz) 
     LCMS: m/z 501 [M+H] +   
     HPLC retention time: 1.53 min (analysis condition U) 
     Example 805 
     Compound F6-20 
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid (500 g) was dissolved in a mixture of DMA (9.4 L), acetic anhydride (270 ml) and DIPEA (1170 ml) under nitrogen stream. The mixture was stirred at 90° C. for 1 hr. After cooling to room temperature, the mixture was added with methanol (3.525 L) and subsequently with distilled water (5.875 L). The precipitated solid was filtered, collected, washed twice with the mixture solution (methanol:water=3:5, 1.41 L), and then dried to obtain the title compound (389.6 g, 85%). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.70 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.04 (1H, s), 8.00 (1H, s), 7.61 (1H, d, J=8.5 Hz), 7.34 (1H, s), 3.64-3.57 (4H, m), 3.27-3.18 (2H, m), 2.82-2.66 (4H, m), 2.39-2.28 (1H, m), 1.96-1.87 (2H, m), 1.76 (6H, s), 1.69-1.53 (2H, m), 1.29 (3H, t, J=7.3 Hz) 
     LCMS: m/z 483 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition U) 
     Hydrochloric Acid Salt of Compound F6-20 
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (400 g) was dissolved in a mixture solvent of methylethyl ketone (4.8 L), acetic acid (1.44 L) and distilled water (1.68 L) at room temperature. The resulting solution was added dropwise to the mixture of ethanol (12 L) and 2 N hydrochloric acid (0.8 L). The precipitated solid was filtered, washed with ethanol (2 L), and dried to obtain hydrochloric acid salt of Compound F6-20 (357 g). 
       1 H-NMR (400 MHz, DMSO-d 6 ) δ: 12.83 (1H, s), 10.78 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.06 (1H, s), 8.01 (1H, s), 7.61 (1H, d, J=8.1 Hz), 7.37 (1H, s), 4.02 (2H, m), 3.85 (2H, m), 3.51 (2H, m), 3.34 (1H, m), 3.32 (2H, m), 3.15 (2H, m), 2.81 (2H, dd, J=11.98, 11.7 Hz), 2.72 (2H, q, J=7.5 Hz), 2.23 (2H, m), 1.89 (2H, m), 1.77 (6H, s), 1.29 (3H, t, J=7.5 Hz) 
     FABMS: m/z 483.4 [M+H] +   
     Example 806 
     Compound F6-22 
     9-Ethyl-6,6-dimethyl-10-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     From the filtrate solution obtained from the synthesis of Compound F6-20, the title compound was obtained. 
       1 H-NMR (400 MHz DMSO-D 6 ) δ: 12.56 (1H, s), 8.32 (1H, d, J=7.9 Hz), 7.96 (1H, s), 7.45-7.59 (3H, m), 3.55-3.62 (4H, m), 3.36-3.50 (2H, m), 2.75-2.86 (2H, m), 2.71 (2H, q, J=7.5 Hz), 2.45-2.56 (4H, m), 2.27-2.38 (1H, m), 1.73-1.84 (2H, m), 1.69 (6H, s), 1.43-1.58 (2H, m), 1.21 (3H, t, J=7.5 Hz). 
     LCMS: m/z 483 [M+H] +   
     HPLC retention time: 1.52 min (analysis condition U) 
     Example 807 
     Compound PR8 
     9-Ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid (11 g) was dissolved in Eaton&#39;s reagent (200 g) and stirred at room temperature for 30 min. The reaction solution was diluted with acetonitrile (200 ml) and distilled water (400 ml). The precipitated solid was collected by filtration, washed with distilled water, and then dried. The crude product was dissolved in DMA (45 ml), diluted with acetonitrile (20 ml) and distilled water (18 ml), and re-precipitated to obtain the title compound (6.62 g, 70%). 
       1 H-NMR (400 MHz DMSO-D 6 ) δ: 12.79 (1H, s), 8.32-8.29 (2H, m), 8.06 (1H, s), 8.01 (1H, s), 7.62 (1H, dd, J=1.3, 7.9 Hz), 2.78 (2H, q, J=7.5 Hz), 1.75 (6H, s), 1.20 (3H, t, J=7.5 Hz) 
     LCMS: m/z 441 [M+H] +   
     HPLC retention time: 3.17 min (analysis condition U) 
     Example 808 
     Compound PR9-1 
     8-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     The dioxane solution (50 ml) of 9-ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (5.0 g), 1,4-dioxa-8-aza-spiro[4.5]decane (2.08 ml), Pd 2 (dba) 3  (520 mg), and S-Phos (963 mg) was flushed with nitrogen gas, added with NaHMDS (1M, THF solution 40 ml), and stirred at 60° C. for 1 hr. The resulting mixture was diluted with ethyl acetate (200 ml). The organic layer was washed three times with 10% brine, and then concentrated under reduced pressure to obtain the title compound as a crude product. This crude product was used for the next step without further purification. 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 2.78 min (analysis condition U) 
     Example 809 
     Compound PR9-2 
     9-Ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     As a by-product of Compound PR9-1, the target compound was obtained according to silica gel column separation of Example 810. 
     LCMS: m/z 315 [M+H] +   
     HPLC retention time: 2.77 min (analysis condition U) 
     Example 810 
     Compound PR10-1 
     9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     8-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile, which had been prepared in Example 809, was dissolved in THF (10 ml), added with 5 N hydrochloric acid (50 ml), and the mixture was stirred for 17 hrs. The reaction mixture was neutralized with 5 N aqueous solution of sodium hydroxide and diluted with ethyl acetate (200 ml). The organic layer was washed with 10% brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (2.9 g, two step yield 64%). 
       1 H-NMR (400 MHz DMSO-D 6 ) δ: 12.70 (1H, s), 8.32 (1H, d, J=8.4), 8.07 (1H, s), 7.99 (1H, s), 7.60 (1H, dd, J=1.3, 7.9 Hz), 7.42 (1H, s), 3.28 (4H, t, J=5.7), 2.80 (q, 2H, J=7.5 Hz), 2.55 (4H, t, J=5.7), 1.75 (6H, s), 1.31 (3H, t, J=7.5 Hz) 
     LCMS: m/z 412 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition U) 
     Example 811 
     Compound PR11-1 
     9-Ethyl-6,6-dimethyl-11-oxo-8-[4-(3-oxo-piperazin-1-yl)-piperidin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (30 mg) and 2-ketopiperazine (10 mg) were dissolved in THF (2 ml), added with sodium triacetoxy borohydride (30 mg), and the mixture was stirred at 30° C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (20 ml). The organic layer was washed with 10% brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (11.5 mg, yield 32%). 
     LCMS: m/z 496 [M+H] +   
     HPLC retention time: 1.90 min (analysis condition U) 
     Example 812 
     Compound PR11-2 
     9-Ethyl-8-(4-hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     As a by-product of Compound PR11-1, the target compound was obtained. 
     LCMS: m/z 414 [M+H] +   
     HPLC retention time: 2.13 min (analysis condition S) 
     The compounds described in the following Tables 8-10 were synthesized by introducing a corresponding amine to 9-ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile according to the method used for the synthesis of Compound PR9-1. Although the relevant literatures are not entirely known, some amines in which a tertiary alkyl group is attached to the nitrogen atom were prepared according to the method described in Journal of Medicinal Chemistry, 45 (14), 3143-3160, 2002. Alternatively, the preparation was carried out by introducing a corresponding amine to 9-ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile based on the method that is used for the synthesis of Compound PR11-1 (i.e., reductive amination). 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 813 
                 PR9-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-tert-Butyl- piperazin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.63 
                 455 
               
               
                   
               
               
                 814 
                 PR9-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-11-oxo-8- (4-pyrrolidin-1-yl- piperidin-1-yl)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.13 
                 467 
               
               
                   
               
               
                 815 
                 PR9-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4- isopropyl- piperazin-1-yl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.08 
                 441 
               
               
                   
               
               
                 816 
                 PR9-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-(4- methyl-piperazin- 1-yl)-11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.97 
                 413 
               
               
                   
               
               
                 817 
                 PR9-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4-ethyl- piperazin-1-yl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.03 
                 427 
               
               
                   
               
               
                 818 
                 PR9-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8- morpholin-4-yl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.65 
                 400 
               
               
                   
               
               
                 819 
                 PR11-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4-((2R,6S)-2,6- Dimethyl- morpholin-4-yl)- piperidin-1-yl]-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.65 
                 511 
               
               
                   
               
               
                 820 
                 PR11-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8- [1,4′]Bipiperidinyl- 1′-yl-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.63 
                 481 
               
               
                   
               
               
                 821 
                 PR11-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4,4-Difluoro- [1,4′]bipiperidinyl- 1′-yl)-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.70 
                 517 
               
               
                   
               
               
                 822 
                 PR11-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Azetidin-1-yl- piperidin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.55 
                 453 
               
               
                   
               
               
                 823 
                 PR11-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4- hydroxy- [1,4′]bipiperidinyl- 1′-yl)-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.95 
                 497 
               
               
                   
               
               
                 824 
                 PR9-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclopropyl- 4-hydroxy- piperidin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.53 
                 454 
               
               
                   
               
               
                 825 
                 PR11-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4- fluoro- [1,4′]bipiperidinyl- 1′-yl)-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.13 
                 499 
               
               
                   
               
               
                 826 
                 PR9-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-(3- morpholin-4-yl- azetidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.48 
                 455 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 827 
                 PR9-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-11-oxo-8- (3-piperidin-1-yl- azetidin-1-yl)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.57 
                 453 
               
               
                   
               
               
                 828 
                 PR9-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-[4-(1- methyl-piperidin-4- yl)-piperazin-1-yl]- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.70 
                 496 
               
               
                   
               
               
                 829 
                 PR9-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-[4-(4- methyl-piperazin- 1-yl)-piperidin-1- yl]-11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.73 
                 496 
               
               
                   
               
               
                 830 
                 PR11-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclopentyl- piperazin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.12 
                 467 
               
               
                   
               
               
                 831 
                 PR11-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-[4-(2- hydroxy- ethylamino)- piperidin-1-yl]-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 1.90 
                 457 
               
               
                   
               
               
                 832 
                 PR-11-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-[4-(3- hydroxy- propylamino)- piperidin-1-yl]-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 S 
                 1.90 
                 471 
               
               
                   
               
               
                 833 
                 PR9-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-(4- methyl-4- morpholine-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.00 
                 497 
               
               
                   
               
               
                 834 
                 PR9-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-[4-(1- ethyl-cyclobutyl)- piperazine-1-yl]- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 Y 
                 2.25 
                 481 
               
               
                   
               
               
                 835 
                 PR9-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4- ethyl-4- morpholine-4-yl- piperidine-1-yl)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 Y 
                 2.17 
                 511 
               
               
                   
               
               
                 836 
                 PR9-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-(4- isopropyl-4- morpholine-4-yl- piperidine-1-yl)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.12 
                 525 
               
               
                   
               
               
                 837 
                 PR9-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-11-oxo-8- [4-(1-propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.28 
                 495 
               
               
                   
               
               
                 838 
                 PR9-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-[4-(1- isopropyl- cyclobutyl)- piperazine-1-yl]- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 U 
                 2.25 
                 495 
               
               
                   
               
               
                 839 
                 PR9-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-(2- morpholine-4-yl- ethylamino)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile 
                 Y 
                 1.85 
                 443 
               
               
                   
               
               
                 840 
                 PR9-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-11-oxo-6- (2-piperidine-1-yl- ethylamino)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile 
                 Y 
                 1.85 
                 441 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 841 
                 PR11-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Amino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 U 
                 1.92 
                 413 
               
               
                   
               
               
                 842 
                 PR11-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-6,6- dimethyl-8-(4- 2,2,3,3,5,5,6,6-d8- morpholine-4-yl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H-benzo [b]carbazole-3- carbonitrile 
                 U 
                 1.98 
                 491 
               
               
                   
               
               
                 843 
                 PR9-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-8-[4-(2- methoxy-ethoxy)- piperidine-1-yl]6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 3.23 
                 472 
               
               
                   
               
               
                 844 
                 PR9-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4-(2-Ethoxy- ethoxy)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 3.35 
                 486 
               
               
                   
               
               
                 845 
                 PR9-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropylmethoxy- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 3.50 
                 468 
               
               
                   
               
               
                 846 
                 PR9-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4-(2-Cyclohexyl- ethoxy)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 4.00 
                 524 
               
               
                   
               
               
                 847 
                 PR11-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 2.33 
                 495 
               
               
                   
               
               
                 848 
                 PR11-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 2.15 
                 481 
               
               
                   
               
               
                 849 
                 PR11-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4- Cyclopropylmethoxy- amino)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile  
                 Y 
                 2.15 
                 467 
               
               
                   
               
               
                 850 
                 PR11-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 2.08 
                 453 
               
               
                   
               
               
                 851 
                 PR11-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4- Cyclopropylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 2.13 
                 467 
               
               
                   
               
               
                 852 
                 PR11-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[4- Cyclohexylmethyl- amino)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile 
                 Y 
                 2.42 
                 509 
               
               
                   
               
            
           
         
       
     
     Example 853 
     Compound PR11-22 
     9-Ethyl-8-(4-hydroxyimino-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (30 mg) and hydroxylamine hydrochloric acid salt (10 mg) were dissolved in ethanol (5 ml) and stirred at 60° C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (20 ml). The organic layer was washed with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (23.5 mg, yield 74%). 
     LCMS: m/z 427 [M+H] +   
     HPLC retention time: 3.08 min (analysis condition Y) 
     Example 854 
     Compound PR10-2 
     9-Ethyl-6,6-dimethyl-5-(2-morpholin-4-yl-ethyl)-8-(2-morpholin-4-yl-ethylamino)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Ethyl-6,6-dimethyl-8-(2-morpholin-4-yl-ethylamino)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (10 mg) was dissolved in DMF (1 ml), added with K 2 CO 3  (10 mg) and 1-(2-chloroethyl)morpholine (8 mg), and then stirred at 90° C. for 17 hrs. The reaction mixture was diluted with ethyl acetate (10 ml). The organic layer was washed with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (6.4 mg, yield 58%). 
     LCMS: m/z 556 [M+H] +   
     HPLC retention time: 1.78 min (analysis condition Y) 
     Example 855 
     Compound F7 
     9-Ethyl-6,6-dimethyl-11-oxo-8-[4-(4-oxy-morpholin-4-yl)-piperidin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (400 mg) was dissolved in trifluoroethanol (80 ml), added with 30% hydrogen peroxide solution (0.8 ml), and the mixture was stirred at 60° C. for 17 hrs. The reaction mixture was concentrated to 30 ml and diluted with water (20 ml). The precipitated matter was collected by filtration and dried to obtain the title compound (375 mg, yield 90%). 
     LCMS: m/z 499 [M+H] +   
     HPLC retention time: 2.05 min (analysis condition U) 
     Example 856 
     Compound FR1 
     6-Cyano-2-[1-(4-ethyl-3-iodophenyl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     4-(4-Ethyl-3-iodo-phenyl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester (1.00 g, 2.40 mmol) was dissolved in NMP (4 ml), added with cesium carbonate (1.56 g, 4.80 mmol, 2.0 eq.), and the mixture was stirred for 5 min. The NMP solution (2 ml) of 4-chloro-3-nitro-benzonitrile (542 mg, 2.88 mmol, 1.2 eq.) was added thereto, and the mixture was stirred at 50° C. for 64 hrs under nitrogen atmosphere. After cooling to room temperature, ethyl acetate (20 ml) was added and the organic layer was washed with saturated aqueous solution of ammonium chloride (20 ml). The organic layer was further washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white amorphous, 320 mg, 26%). 
     LCMS: m/z 516 [M+H] +   
     Example 857 
     Compound FR2 
     6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-[1-(4-ethyl-3-iodophenyl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester was converted to obtain the title compound in the same manner as the method for Compound PR6. 
     LCMS: m/z 558 [M+H] +   
     Example 858 
     Compound FR3 
     6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid hydroiodic acid salt 
     
       
         
         
             
             
         
       
     
     To obtain the title compound, 6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid tert-butyl ester was deprotected by using trimethylsilyl iodide in the same manner as the method for Compound PR7. 
     LCMS: m/z 502 [M+H] +   
     Example 859 
     Compound FR4 
     9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid hydroiodic acid salt was converted in the same method as Example 805 to obtain the target compound. 
     LCMS: m/z 484 [M+H] +   
     Example 860 
     Compound LB1 
     2-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-2-methyl-propionic acid 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid by carrying out amination in the same manner as the method for synthesizing Compound PR6. 
     LCMS: m/z 361 [M+H] +   
     Example 861 
     Compound LB2 
     2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     2-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-2-methyl-propionic acid was converted in the same manner as the method for synthesizing Compound PR5-1 to obtain the title compound. 
     LCMS: m/z 658 [M+H] +   
     HPLC retention time: 2.76 min (analysis condition U) 
     Example 862 
     Compound LB3 
     2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid tert-butyl ester was deprotected in the same manner as the method for preparing Compound PR7 to obtain the title compound. 
     LCMS: m/z 602 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition U) 
     Example 863 
     Compound LB4 
     9-Ethyl-3-iodo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid was converted in the same manner as Example 805 to obtain the title compound. 
     LCMS: m/z 584 [M+H] +   
     HPLC retention time: 2.25 min (analysis condition U) 
     The compounds described in the following Table 11 were converted and prepared from 9-ethyl-3-iodo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5,6-dihydro-benzo[b]carbazol-11-one according to the method described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 11 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 864 
                 LB5-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[9-Ethyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-yl]-benzamide 
                 Y 
                 1.78 
                 577 
                 B2-10 
               
               
                   
               
               
                 865 
                 LB5-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Ethyl-3- ethylsulfanyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-5,6- dihydro- benzo[b]carbazole- 11-one 
                 Y 
                 2.28 
                 518 
                 B2-17 
               
               
                   
               
               
                 866 
                 LB5-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[9-Ethyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-yl]-acetamide 
                 Y  
                 1.50 
                 515 
                 B2-10 
               
               
                   
               
            
           
         
       
     
     Example 867 
     Compound AZ1 
     Methanesulfonic acid (2-fluoropyridin-4-yl)methyl ester 
     
       
         
         
             
             
         
       
     
     (2-Fluoropyridin-4-yl) methanol (1 g) was dissolved in DCM (40 ml), added with TEA (3.3 ml) and mesyl chloride (0.67 ml), and the mixture was stirred at 0° C. for 1 hr. The mixture was concentrated and then purified by silica gel column (n-hexane/ethyl acetate=4/1) to obtain the title compound (1.18 g, 77%). 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 3.21 (3H, s), 5.38 (2H, s), 7.22 (1H, s), 7.39 (1H, d, J=5.0), 8.29 (1H, d, J=5.0) 
     Example 868 
     Compound AZ2 
     (2-Fluoropyridin-4-yl)acetonitrile 
     
       
         
         
             
             
         
       
     
     To the DMF (28 ml) solution of methanesulfonic acid (2-fluoropyridin-4-yl)methyl ester (1.16 g), sodium cyanide (0.42 g) was added and the mixture was stirred at 80° C. for 1 hr. The mixture was diluted with ethyl acetate (100 ml), and washed with 15% brine and distilled water in order. The organic layer was concentrated and purified by silica gel column (n-hexane/ethyl acetate=5/1) to obtain the title compound (278 mg, 36%). 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 4.22 (2H, s), 7.18 (1H, s), 7.36 (1H, d, J=5.0), 8.27 (1H, d, J=5.0) 
     Example 869 
     Compound AZ3 
     (2-Fluoropyridin-4-yl) 2 -methylpropionitrile 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from (2-fluoropyridin-4-yl) acetonitrile in the same manner as the method for Compound K2. 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 1.72 (6H, s), 7.34 (1H, s), 7.53 (1H, d, J=5.3), 8.31 (1H, d, J=5.3) 
     Example 870 
     Compound AZ4 
     4-(2-Fluoropyridin-4-yl)-4-methyl-3-oxopentanoic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from (2-fluoropyridin-4-yl) 2-methylpropionitrile in the same manner as the method for Compound K3. 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 1.13 (3H, t, J=7.3), 1.48 (6H, s), 3.57 (2H, s), 4.01 (2H, q, J=7.3), 7.12 (1H, s), 7.25 (1H, d, J=5.3), 8.22 (1H, d, J=5.3) 
     Example 871 
     Compound AZ5 
     6-Cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     The title compound was prepared from 4-(2-fluoropyridin-4-yl)-4-methyl-3-oxopentanoic acid ethyl ester in the same manner as the method for Compound K4 and Compound K5. 
     LCMS: m/z 352 [M+H] +   
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 1.05 (3H, t, J=7.3), 1.82 (6H, s), 3.98 (2H, q, J=7.3), 6.99-7.02 (2H, m), 7.16 (1H, dd, J=8.4, 1.5), 7.97 (1H, s), 8.05-8.11 (2H, m) 
     Example 872 
     Compound AZ6 
     6-Cyano-2-[1-(2-(4-morpholin-4-yl-piperidin-1-yl))pyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (110 mg) was dissolved in NMP (3.3 ml), added with 4-morpholin-4-yl-piperidine (319 mg), and stirred in a sealing tube at 120° C. for 1 hr. The reaction mixture was diluted with ethyl acetate (50 ml) and washed with 15% brine and distilled water in order. The organic layer was concentrated and purified by silica gel column (DCM/methanol=20/1) to obtain the title compound (120 mg, 76%). 
     LCMS: m/z 502 [M+H] +   
     Example 873 
     Compound AZ7-1 
     5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b]carbazole-8-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     6-Cyano-2-[1-(2-(4-morpholin-4-yl-piperidin-1-yl))pyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (110 mg) was dissolved in Eaton&#39;s reagent (2.5 ml) and stirred at 55° C. for 17 hrs. The reaction mixture was neutralized with saturated aqueous solution of sodium bicarbonate. The precipitated matters were collected by filtration, and then washed with water to obtain the title compound (72 mg, 70%). 
     LCMS: m/z 474 [M+H] +   
     HPLC retention time: 1.17 min (analysis condition U) 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 1.38 (2H, m), 1.75 (6H, s), 1.88 (2H, m), 2.44 (5H, m), 2.94 (2H, m), 3.57 (4H, m), 4.58 (2H, m), 7.10 (1H, s), 7.32 (1H, s), 7.75 (1H, d, J=8.4), 8.00 (2H, m), 8.15 (1H, d, J=8.4), 8.85 (1H, s), 12.3 (1H, s) 
     Example 874 
     Compound AZ7-2 
     5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b]carbazole-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b]carbazole-8-carboxylic acid amide (54 mg) was dissolved in DMF (1 ml), added with thionyl chloride (25 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water. The precipitated matters were collected by filtration to obtain the title compound (25 mg, 49%). 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 1.55 min (analysis condition U) 
       1 H-NMR (270 MHz DMSO-d 6 ) δ: 1.36 (2H, m), 1.76 (6H, s), 1.89 (2H, m), 2.44 (5H, m), 2.95 (2H, m), 3.57 (4H, m) 4.58 (2H, m), 7.10 (1H, s), 7.59 (1H, d, J=8.0), 7.99 (1H, s), 8.29 (1H, d, J=8.0), 8.86 (1H, s), 12.7 (1H, s) 
     The compounds described in the following Tables 12-13 were synthesized by introducing a corresponding amino group to 6-cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester and forming a ring according to the method that is used for the synthesis of Compound AZ7-1. Furthermore, the preparation was carried out by converting the substituent group at position 3 from a carboxamide group to a cyano group according to the method that is used for the synthesis of Compound AZ7-2. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 Ex- 
                   
                   
                   
                 HPLC 
                 Re- 
                   
               
               
                 ample 
                 Comp. 
                   
                   
                 Con- 
                 tention 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 dition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 875 
                 AZ7-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[4-((2R,6S)-2,6- Dimethyl-morpholine- 4-yl)-piperidine-1- yl]-5,5-dimethyl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.32 
                 502 
               
               
                   
               
               
                 876 
                 AZ7-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[4-((2R,6S)-2,6- Dimethyl-morpholine- 4-yl)-piperidine-1- yl]-5,5-dimethyl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.70 
                 484 
               
               
                   
               
               
                 877 
                 AZ7-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[1,4′]Bipiperidinyl- 1′-yl-5,5-dimethyl- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.30 
                 472 
               
               
                   
               
               
                 878 
                 AZ7-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3-(4- methyl-4-morpholine- 4-yl-piperidine-1-yl)- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 Y 
                 1.00 
                 488 
               
               
                   
               
               
                 879 
                 AZ7-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3-(4- methyl-4-morpholine- 4-yl-piperidine-1-yl)- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.62 
                 470 
               
               
                   
               
               
                 880 
                 AZ7-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Cyclobutyl- piperazine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 Y  
                 1.22 
                 444 
               
               
                   
               
               
                 881 
                 AZ7-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Cyclobutyl- piperazine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.55 
                 426 
               
               
                   
               
               
                 882 
                 AZ7-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[1,4′]Bipiperidinyl- 1′-yl-5,5-dimethyl- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.73 
                 454 
               
               
                   
               
               
                 883 
                 AZ7-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3- morpholine-4-yl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide  
                 U 
                 1.33 
                 391 
               
               
                   
               
               
                 884 
                 AZ7-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3- morpholine-4-yl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.77 
                 373 
               
               
                   
               
               
                 885 
                 AZ7-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[4-(1-Ethyl- cyclobutyl)- piperazine-1-yl]5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.93 
                 464 
               
               
                   
               
               
                 886 
                 AZ7-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Ethyl-4- morpholine-4-yl- piperidine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 Y 
                 1.18 
                 502 
               
               
                   
               
               
                 887 
                 AZ7-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Ethyl-4- morpholine-4-yl- piperidine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.78 
                 484 
               
               
                   
               
               
                 888 
                 AZ7-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-[4-(1-Ethyl- cyclobutyl)- piperazine-1-yl]-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 Y 
                 1.25 
                 472 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 889 
                 AZ7-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Isopropyl- 4-morpholine-4- yl-piperidine-1- yl)-5,5-dimethyl- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.27 
                 516 
               
               
                   
               
               
                 890 
                 AZ7-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3- (4-morpholine-4- yl-4-propyl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.36 
                 516 
               
               
                   
               
               
                 891 
                 AZ7-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl-3- (4-morpholine-4- yl-4-propyl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.68 
                 498 
               
               
                   
               
               
                 892 
                 AZ7-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Isopropyl- 4-morpholine-4- yl-piperidine-1- yl)-5,5-dimethyl- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.60 
                 498 
               
               
                   
               
               
                 893 
                 AZ7-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl- 11-oxo-3-[4-(1- propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.58 
                 486 
               
               
                   
               
               
                 894 
                 AZ7-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5,5-Dimethyl- 11-oxo-3-[4-(1- propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.97 
                 468 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 14 were synthesized from (2-chloro-3-fluoropyridin-4-yl)methanol according to the method that is used for the synthesis of Compound AZ1 to AZ7-2. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 14 
               
               
                   
               
               
                 Ex- 
                   
                   
                   
                   
                   
                   
               
               
                 am 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 895 
                 AZ7-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Fluoro-5,5- dimethyl-3-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.37 
                 492 
               
               
                   
               
               
                 896 
                 AZ7-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Fluoro-5,5- dimethyl-3-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.74 
                 474 
               
               
                   
               
               
                 897 
                 AZ7-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Fluoro-5,5- dimethyl-11-oxo-3- [4-(3-oxo- piperazin-1-yl)- piperidin-1-yl]-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.32 
                 505 
               
               
                   
               
               
                 898 
                 AZ7-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3- [1,4′]Bipiperidinyl- 1′-yl-4-fluoro-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide 
                 U 
                 1.45 
                 490 
               
               
                   
               
               
                 899 
                 AZ7-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3- [1,4′]Bipiperidinyl- 1′-yl-4-fluoro-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile 
                 U 
                 1.87 
                 472 
               
               
                   
               
            
           
         
       
     
     Example 900 
     Compound BZ1 
     2-Cyano-4-hydrazinopyridine 
     
       
         
         
             
             
         
       
     
     4-Chloro-2-cyanopyridine (1 g) was dissolved in hydrazine monohydrate (1 ml) and 1,4-dioxane (10 ml), and stirred overnight under reflux. The reaction solution was diluted with water (30 ml) and extracted repeatedly with ethyl acetate. The organic layer was concentrated to obtain the title compound as a crude product, which was used for the next step without further purification. 
     LCMS: m/z 135 [M+H] +   
     Example 901 
     Compound BZ2-1 
     8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[f]pyrido[4,3-b]indol-3-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-cyano-4-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound. 
     LCMS: m/z 318 [M+H] +   
     HPLC retention time: 2.10 min (analysis condition U) 
     Example 902 
     Compound BZ2-2 
     3-Chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[f]pyrido[4,3-b]indol-11-one 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-chloro-4-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound. 
     LCMS: m/z 327, 329 [M+H] +   
     HPLC retention time: 1.80 min (analysis condition S) 
     Example 903 
     Compound CZ1 
     2-Bromo-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-bromo-6-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound. 
     LCMS: m/z 371, 373 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition U) 
     Example 904 
     Compound CZ2 
     8-Methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method 1 for Compound A5-2, 2-bromo-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one was subjected to cyanation to obtain the title compound. 
     LCMS: m/z 318 [M+H] +   
     HPLC retention time: 2.35 min (analysis condition U) 
     Example 905 
     Compound CZ3 
     8-Hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A6, 8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to demethylation to obtain the title compound. 
     LCMS: m/z 304 [M+H] +   
     HPLC retention time: 1.72 min (analysis condition S) 
     Example 906 
     Compound CZ4 
     Trifluoromethanesulfonic acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound B1, 8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to trifluoromethanesulfone esterification to obtain the title compound. 
     LCMS: m/z 436 [M+H] +   
     HPLC retention time: 3.32 min (analysis condition Y) 
     Example 907 
     Compound CZ5-1 
     10,10-Dimethyl-5-oxo-8-piperazin-1-yl-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound B2-1, trifluoromethanesulfonic acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester was introduced with piperazine to obtain the title compound. 
     LCMS: m/z 372 [M+H] +   
     HPLC retention time: 1.17 min (analysis condition S) 
     Example 908 
     Compound CZ5-2 
     10,10-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound B2-1, trifluoromethanesulfonic acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester was introduced with 4-morpholin-4-yl piperidine to obtain the title compound. 
     LCMS: m/z 456 [M+H] +   
     HPLC retention time: 1.68 min (analysis condition U) 
     Example 909 
     Compound CZ6 
     8-(4-Cyclobutyl-piperazin-1-yl)-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound B3-32, 10,10-dimethyl-5-oxo-8-piperazin-1-yl-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to reductive amination with cyclobutanone to obtain the title compound. 
     LCMS: m/z 426 [M+H] +   
     HPLC retention time: 1.60 min (analysis condition U) 
     Example 910 
     Compound DZ1 
     6-Ethynyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (1 g) was dissolved in acetonitrile (50 ml), added with PdCl 2 (CH 3 CN) 2  (45 mg), X-phos (168 mg), CsCO 3  (1.2 g) and trimethylsilylacetylene (0.9 ml), and the mixture was stirred at 85° C. for 2 hrs. The reaction mixture was diluted with ethyl acetate (100 ml). The organic layer was washed twice with 10% brine and concentrated under reduced pressure. The resulting residues were dissolved in THF (10 ml), added with the THF solution (4 ml) comprising tetrabutylammonium fluoride and stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (100 ml). The organic layer was washed twice with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (n-hexane/ethyl acetate=9/1) to obtain the title compound (346 mg, two step yield 43%). 
     LCMS: m/z 229 [M+H] +   
     Example 911 
     Compound DZ2 
     6-Ethyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     6-Ethynyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (346 mg) was dissolved in ethanol:THF (=2:1 mixture solvent, 20 ml), added with 10% Pd/C (170 mg), and then the mixture was stirred at room temperature for 1 hr under hydrogen atmosphere. The catalyst was removed by filtration and the organic layer was concentrated under reduced pressure to obtain the title compound (322 mg, yield 91%). 
     LCMS: m/z 233 [M+H] +   
     Example 912 
     Compound DZ3 
     2-Bromo-7-ethyl-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-bromo-6-hydrazinopyridine and 6-ethyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound. 
     LCMS: m/z 399, 401 [M+H] +   
     HPLC retention time: 3.35 min (analysis condition Y) 
     Example 913 
     Compound DZ4 
     7-Ethyl-8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method 1 for Compound A5-2, 2-bromo-7-ethyl-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one was subjected to cyanation to obtain the title compound. 
     LCMS: m/z 346 [M+H] +   
     HPLC retention time: 3.05 min (analysis condition Y) 
     Example 914 
     Compound DZ5 
     7-Ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A5, 7-ethyl-8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to demethylation to obtain the title compound. 
     LCMS: m/z 332 [M+H] +   
     HPLC retention time: 2.60 min (analysis condition Y) 
     Example 915 
     Compound DZ6-1 
     Trifluoro-methanesulfonic acid 2-cyano-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound B1, 7-ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to trifluoromethanesulfone esterification to obtain the title compound. 
     LCMS: m/z 464 [M+H] +   
     HPLC retention time: 3.50 min (analysis condition Y) 
     The compounds described in the following Table 15 were prepared from trifluoro-methanesulfonic acid 2-cyano-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester and corresponding amine according to the method that is used for the synthesis of Compound B2-10. The compounds of Example 919 and Example 920 were obtained as a by-product of the reaction. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 15 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
               
               
                 ple 
                   
                 Comp. 
                   
                 Condi- 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 916 
                 DZ7-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Cyclobutyl- piperazine-1-yl)-7- ethyl-10,10-dimethyl- 5-oxo-10,11-dihydro- 5H-1,11-diaza-benzo [b]fluorene- 2-carbonitrile 
                 Y 
                 1.83 
                 454 
               
               
                   
               
               
                 917 
                 DZ7-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Ethyl-10,10-dimethyl- 8-(4-morpholine- 4-yl-piperidine-1-yl)- 5-oxo-10,11-dihydro- 5H-1,11-diaza-benzo [b]fluorene- 2-carbonitrile 
                 Y 
                 1.85 
                 484 
               
               
                   
               
               
                 918 
                 DZ7-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Ethyl-10,10-dimethyl- 8-morpholine-4-yl-5- oxo-10,11-dihydro-5H- 1,11-diaza- benzo[b]fluorene-2- carbonitrile 
                 Y 
                 3.02 
                 401 
               
               
                   
               
               
                 919 
                 DZ7-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Ethyl-10,10-dimethyl- 5-oxo-10,11-dihydro- 5H-1,11-diaza- benzo[b]fluorene-2- carbonitrile 
                 Y 
                 3.07 
                 316 
               
               
                   
               
               
                 920 
                 DZ7-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Ethyl-10,10-dimethyl- 2-(morpholine-4- carbonyl)-8-morpholine- 4-yl-10,11-dihydro- 1,11-diaza-benzo[b] fluorene-5-one 
                 Y 
                 2.70 
                 489 
               
               
                   
               
            
           
         
       
     
     Example 921 
     Compound DZ6-2 
     8-(2-Diethylamino-ethoxy)-11-(2-diethylamino-ethyl)-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method used for synthesizing Compound A7-17, 7-ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was alkylated to obtain the title compound. 
     LCMS: m/z 530 [M+H] +   
     HPLC retention time: 1.38 min (analysis condition Y) 
     Example 922 
     Compound EZ1 
     2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic acid ethyl ester 
     
       
         
         
             
             
         
       
     
     2-Bromo-6-methoxypyridine (7.0 g), ethyl isobutyrate (4.75 g), tri t-butylphosphine (300 mg) and Pd 2 (dba) 3  (680 mg) were dissolved in toluene (200 ml) under nitrogen atmosphere, added with THF solution of LiHMDS (1.6 M, 24 ml), and the mixture was stirred at 100° C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (300 ml), and washed three times with 15% brine (200 ml). The organic layer was concentrated under reduced pressure and the resulting residues were purified by silica gel column (n-hexane/ethyl acetate=4/1) to obtain the title compound (5.353 g, yield 60%). 
     LCMS: m/z 224 [M+H] +   
     Example 923 
     Compound EZ2 
     2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic acid 
     
       
         
         
             
             
         
       
     
     2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic acid ethyl ester (5.33 g) was dissolved in methanol (200 ml), added with 5 N aqueous solution of potassium hydroxide (25 ml), and then stirred under reflux. The reaction mixture was concentrated and neutralized with 2 N hydrochloric acid. The precipitated matters were collected by filtration and dried to obtain the title compound (3.55 g). 
     LCMS: m/z 196 [M+H] +   
     Example 924 
     Compound EZ3 
     4-(6-Methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized from 2-(6-methoxy-pyridin-2-yl)-2-methyl-propionic acid and mono-tert-butyl malonic acid according to the method used for the synthesis of Compound PR4. The resultant was used for the next step without further purification. 
     Example 925 
     Compound EZ4-1 
     6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound PR5-1, the title compound was synthesized from 4-(6-methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester and 4-chloro-3-nitrobenzonitrile 
     LCMS: m/z 392 [M+H] +   
     Example 926 
     Compound EZ4-2 
     6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound FR1, the title compound was synthesized from 4-(6-methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester and 4-chloro-3-nitrobenzonitrile. 
     LCMS: m/z 393 [M+H] +   
     Example 927 
     Compound EZ5-1 
     6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound PR7, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid tert-butyl ester. 
     LCMS: m/z 336 [M+H] +   
     Example 928 
     Compound EZ5-2 
     6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound PR7, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester. 
     LCMS: m/z 337 [M+H] +   
     Example 929 
     Compound EZ6-1 
     2-Methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound AZ7-1, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid. 
     LCMS: m/z 336 [M+H] +   
     HPLC retention time: 1.98 min (analysis condition S) 
     Example 930 
     Compound EZ6-2 
     2-Methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carboxylic acid amide 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound AZ7-1, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid. 
     LCMS: m/z 337 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition S) 
     Example 931 
     Compound EZ7-1 
     2-Methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound AZ7-2, the title compound was synthesized from 2-methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carboxylic acid amide. 
     LCMS: m/z 318 [M+H] +   
     HPLC retention time: 2.60 min (analysis condition S) 
     Example 932 
     Compound EZ7-2 
     2-Methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound AZ7-2, the title compound was synthesized from 2-methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carboxylic acid amide. 
     LCMS: m/z 319 [M+H] +   
     HPLC retention time: 3.18 min (analysis condition S) 
     Example 933 
     Compound EZ8-1 
     2-Hydroxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound A5, 2-methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carbonitrile was demethylated to synthesize the title compound. 
     LCMS: m/z 304 [M+H] +   
     HPLC retention time: 1.70 min (analysis condition U) 
     Example 934 
     Compound EZ8-2 
     2-Hydroxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile 
     
       
         
         
             
             
         
       
     
     According to the method that is used for the preparation of Compound A5, 2-methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile was demethylated to synthesize the title compound. 
     LCMS: m/z 305 [M+H] +   
     HPLC retention time: 2.17 min (analysis condition U) 
     The compounds described in the following Table 16 were synthesized from 2-hydroxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carbonitrile or from 2-hydroxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile according to the method described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 16 
               
               
                   
               
               
                 Ex- 
                   
                   
                   
                   
                   
                   
                   
               
               
                 am- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                 Compound 
                 Con- 
                 tion 
                   
                 Meth- 
               
               
                 No. 
                 No. 
                 Structure 
                 Name 
                 dition 
                 Time 
                 m/z 
                 od 
               
               
                   
               
             
            
               
                 935 
                 EZ9-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Trifluoro- methanesulfonic acid 8-cyano- 11,11-dimethyl- 5-oxo-10,11- dihydro-5H- pyrido[2,3- b]carbazol-2-yl ester 
                 U 
                 2.93 
                 436 
                 B1 
               
               
                   
               
               
                 936 
                 EZ9-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 11,11-Dimethyl- 5-oxo-2-(tetra- hydro-pyran- 4-yloxy)-10,11- dihydro-5H- pyrido[2,3- b]carbazole-8- carbonitrile 
                 U 
                 2.57 
                 388 
                 A7-1 
               
               
                   
               
               
                 937 
                 EZ9-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2- Diethylamino- ethoxy)-11,11- dimethyl-5-oxo- 10,11-dihydro- 5H-pyrido[2,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.63 
                 403 
                 A7-17 
               
               
                   
               
               
                 938 
                 EZ9-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2- Diethylamino- ethoxy)-10-(2- diethylamino- ethyl)-11,11- dimethyl-5-oxo- 10,11-dihydro- 5H-pyrido[2,3- b]carbazole-8- carbonitrile 
                 Y 
                 1.82 
                 502 
                 A7-17 
               
               
                   
               
               
                 939 
                 EZ9-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(2- Diethylamino- ethoxy)-11,11- dimethyl-5-oxo- 5,11-dihydro- benzo[4,5]furo [3,2-g]quinoline- 8-carbonitrile 
                 Y 
                 1.77 
                 404 
                 A7-17 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 17 were synthesized from Compound W3 and corresponding halide by alkylation of hydroxyl group according to the method that is used for the synthesis of Compound A7-17. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 17 
               
               
                   
               
               
                   
                   
                   
                   
                 HPLC 
                 Reten- 
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 940 
                 W4-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(2-Dimethylamino- ethoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile 
                 1 
                 0.96 
                 374.0 
               
               
                   
               
               
                 941 
                 W4-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(3-Dimethylamino- propoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile 
                 1 
                 0.92 
                 388.0 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 18 were synthesized according to the method shown below. Specifically, Compound GT1-1 was prepared from Compound J2 and phenylhydrazine according to the method that is used for the synthesis of Compound A3 and Compound A4. Subsequently, in accordance with the methylation carried out in the same manner as Compound A10-1, Compound GT1-2 was prepared. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 18 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 942 
                 GT1- 1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.36 
                 292.0 
                 A3 A4 
               
               
                   
               
               
                 943 
                 GT1- 2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Methoxy-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.53 
                 306.0 
                 A10-1 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 19 were synthesized according to the method shown below. Specifically, Compound GT2-1 was prepared from Compound A2 and phenylhydrazine according to the method that is used for the synthesis of Compound A3 and Compound A4. 
     Subsequently, by carrying out the alkylation in the same manner as Compound A10-1, Compound GT2-2 and Compound GT2-8 were prepared. 
     To obtain the compounds of the Table, chemical conversion of Compound GT2-1 or the 5-alkylate of Compound GT2-1 was achieved by using in combination the functional group modifications (e.g., demethylation according to the method used for the preparation of Compound A6 and subsequent introduction of a functional group, etc.) as explained before and described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 19 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 944 
                 GT2-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.30 
                 292.0 
                 A3 A4 
               
               
                   
               
               
                 945 
                 GT2-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Methoxy-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.55 
                 306.0 
                 A10-1 
               
               
                   
               
               
                 946 
                 GT2-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 1.90 
                 391.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 947 
                 GT2-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3- Dihydroxy- propoxy)-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 1.90 
                 366.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 948 
                 GT2-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 F 
                 1.93 
                 377.3 
                 A6 A7-17 
               
               
                   
               
               
                 949 
                 GT2-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-6,6- dimethyl-5- propyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.09 
                 419.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 950 
                 GT2-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Benzyl-8-(2- diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 B 
                 4.83 
                 467.3 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 951 
                 GT2-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-Ethyl-8- methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.94 
                 320.0 
                 A10-1 
               
               
                   
               
               
                 952 
                 GT2-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-5-ethyl- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.16 
                 405.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 953 
                 GT2-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-5- isopropyl-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.02 
                 419.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 954 
                 GT2-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3- Dihydroxy- propoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 C 
                 2.17 
                 352.2 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 955 
                 GT2-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5- Methanesulfonyl- 8-methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 C 
                 2.87 
                 370.1 
                 A9-1 
               
               
                   
               
               
                 956 
                 GT2-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-5- methanesulfonyl- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.20 
                 455.1 
                 A6 A7-17 A9-1 
               
               
                   
               
               
                 957 
                 GT2-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2- Diethylamino- ethoxy)-5-(2- hydroxy-ethyl)- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 H 
                 3.73 
                 421.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 958 
                 GT2-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8- ((2R,3R)-2,3,4- trihydroxy- butoxy)-5,6- dihydro- benzo[b]carbazol- 11-one 
                 H 
                 3.73 
                 382.4 
                 A7-1 A7- 14-2 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 20 were synthesized according to the method shown below. Specifically, by using Compound A2 and phenylhydrazine having a corresponding substituent group, 2 (or 3)-substituted-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-11-one was prepared according to the method that is used for the synthesis of Compound A3 and Compound A4. Subsequently, to obtain the compounds of the Table, chemical conversion of the above compounds was achieved by using in combination the functional group modifications as explained before and described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 20 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 959 
                 GT3-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-Methoxy-3,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.39 
                 306.0 
                 A3 A4 
               
               
                   
               
               
                 960 
                 GT3-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-3,5,6,6- tetramethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 1.97 
                 405.0 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 961 
                 GT3-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3-nitro- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 B 
                 3.86 
                 422.2 
                 A6 A7-17 
               
               
                   
               
               
                 962 
                 GT3-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3- trifluoromethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 2.03 
                 445.0 
                 A6 A7-17 
               
               
                   
               
               
                 963 
                 GT3-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-5-(2- diethylamino- ethyl)-6,6- dimethyl-3-nitro- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 1.74 
                 521.3 
                 A6 A7-17 A10-1 
               
               
                   
               
               
                 964 
                 GT3-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2,6,6-Trimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.03 
                 396.0 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 965 
                 GT3-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 1.99 
                 400.0 
                 A6 A7-17 A7-14-2 
               
               
                   
               
               
                 966 
                 GT3-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Chloro-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.14 
                 416.0 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 967 
                 GT3-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11- oxo-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6,11- dihydro-5H- benzo[b]carbazole- 2-carbonitrile 
                 F 
                 1.90 
                 407.4 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 968 
                 GT3-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-3- trifluoromethoxy-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.31 
                 466.4 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 969 
                 GT3-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3- Dihydroxy- propoxy)-6,6- dimethyl-3- trifluoromethoxy- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 F 
                 2.43 
                 436.4 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 970 
                 GT3-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3- Dihydroxy- propoxy)-3- methoxy-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 B 
                 3.79 
                 396.5 
                 A6 A7-17 A10-1 A7- 14-2 
               
               
                   
               
               
                 971 
                 GT3-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3- Dihydroxy- propoxy)-3- methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 B 
                 3.40 
                 382.4 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 21 were synthesized according to the method shown below. Specifically, by using Compound E1 and phenylhydrazine having a corresponding substituent group, 9-bromo-1-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one or 9-bromo-8-methoxy-6,6-dimethyl-3-trifluoromethoxy-5,6-dihydro-benzo[b]carbazol-11-one was prepared according to the method used for the synthesis of Compound A3 and Compound A4. Subsequently, to obtain the compounds of the Table, chemical conversion of the above compounds was achieved by using in combination the functional group modifications as explained before and described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 972 
                 GT4-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Bromo-8-((R)- 2,3-dihydroxy- propoxy)-6,6- dimethyl-3- trifluoromethoxy- 5,6-dihydro- benzo[b]carbazol- 11-one 
                 C 
                 2.68 
                 514.0 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
               
                 973 
                 GT4-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 9-Bromo-1- chloro-8-((R)-2,3- dihydroxy- propoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 C 
                 2.58 
                 464.0 
                 A6 A7-17 A7- 14-2 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Tables 22-23 were synthesized according to the method shown below. Specifically, catalytic reduction of Compound GT3-3 was carried out according to the method used for the preparation of Compound D2 to prepare Compound GT5-1. 
     Reductive alkylation of Compound GT5-1 was carried out according to the method used for the preparation of Compound B3-32 for the introduction of a methyl group or a benzyl group (Compound GT5-2, Compound GT5-3). 
     Catalytic reduction of Compound GT5-3 was carried out according to the method used for the preparation of Compound D2, and then processed to prepare Compound GT5-4. 
     The resulting amino derivatives of Compound GT5-1 to 4 were reacted with corresponding acyl chloride, isocyanate, or chloroformate according to the method used for the preparation of Compound A9-1 to obtain the compounds of the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 22 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                   
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 HPLC 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 974 
                 GT5-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Amino-8-(2- diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 1.15 
                 392.3 
                 D2 
               
               
                   
               
               
                 975 
                 GT5-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-3- dimethylamino-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 A 
                 1.18 
                 420.2 
                 B3-32 
               
               
                   
               
               
                 976 
                 GT5-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(Benzyl-methyl- amino)-8-(2- diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one 
                 B 
                 3.05 
                 496.4 
                 B3-32 
               
               
                   
               
               
                 977 
                 GT5-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3- methylamino-5,6- dihydro- benzo[b]carbazol- 11-one 
                 B 
                 2.46 
                 406.3 
                 B3-32 D2 
               
               
                   
               
               
                 978 
                 GT5-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Pentanoic acid [8- (2-diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]amide 
                 C 
                 2.52 
                 476.5 
                 A9-1 
               
               
                   
               
               
                 979 
                 GT5-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2,2-dimethyl- 
                 A 
                 1.74 
                 476.4 
                 A9-1 
               
               
                   
                   
                   
                 propionamide 
                   
                   
                   
                   
               
               
                   
               
               
                 980 
                 GT5-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-carbamic acid 2-methoxy-ethyl 
                 A 
                 1.55 
                 494.3 
                 A9-1 
               
               
                   
                   
                   
                 ester 
                   
                   
                   
                   
               
               
                   
               
               
                 981 
                 GT5-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-phenyl-urea 
                 B 
                 3.79 
                 511.3 
                 A9-1 
               
               
                   
               
               
                 982 
                 GT5-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2-phenyl- acetamide 
                 B 
                 3.81 
                 510.4 
                 A9-1 
               
               
                   
               
               
                 983 
                 GT5-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3- trifluoromethyl- benzamide 
                 B 
                 4.47 
                 564.4 
                 A9-1 
               
               
                   
               
               
                 984 
                 GT5-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-(3- trifluoromethyl- 
                 B 
                 4.55 
                 579.4 
                 A9-1 
               
               
                   
                   
                   
                 phenyl)-urea 
                   
                   
                   
                   
               
               
                   
               
               
                 985 
                 GT5-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-carbamic acid 3-trifluoromethyl- 
                 H 
                 5.17 
                 580.1 
                 A9-1 
               
               
                   
                   
                   
                 phenyl ester 
                   
                   
                   
                   
               
               
                   
               
               
                 986 
                 GT5-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2-phenoxy- acetamide 
                 C 
                 2.57 
                 526.1 
                 A9-1 
               
               
                   
               
               
                 987 
                 GT5-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl-3- phenyl-urea 
                 B 
                 3.83 
                 525.6 
                 A9-1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 988 
                 GT5-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl-3- (3-trifluoromethyl- phenyl)-urea 
                 B 
                 4.58 
                 593.4 
                 A9-1 
               
               
                   
               
               
                 989 
                 GT5-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Benzyl-1-[8-(2- diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl- urea 
                 B 
                 3.81 
                 539.4 
                 A9-1 
               
               
                   
               
               
                 990 
                 GT5-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-N-methyl-3- trifluoromethyl- benzamide 
                 B 
                 4.15 
                 578.3 
                 A9-1 
               
               
                   
               
               
                 991 
                 GT5-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]N-methyl-2- phenoxy- acetamide 
                 C 
                 2.62 
                 540.4 
                 A9-1 
               
               
                   
               
               
                 992 
                 GT5-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-tert-Butyl- phenyl)-1-[8-(2- diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl- 
                 F 
                 2.45 
                 581.6 
                 A9-1 
               
               
                   
                   
                   
                 urea 
                   
                   
                   
                   
               
               
                   
               
               
                 993 
                 GT5-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-(4- methoxy-phenyl)- 
                 B 
                 3.77 
                 555.4 
                 A9-1 
               
               
                   
                   
                   
                 1-methyl-urea 
                   
                   
                   
                   
               
               
                   
               
               
                 994 
                 GT5-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]carbamic acid phenyl ester 
                 A 
                 1.89 
                 512.2 
                 A9-1 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 24 were synthesized according to the method shown below. Specifically, having Compound T22-1 as a starting material, 8-[(4R,5R)-5-(tert-butyl-dimethylsilanyloxymethyl)-2,2-dimethyl-11,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-11-oxo-benzo[b]carbazole-3-carboxylic acid was prepared according to the method that is used for the preparation of Compound B2-28. 
     The resulting carboxylic acid was subjected to dehydrating condensation with corresponding amine, alcohol according to the method that is used for the preparation of Compound A9-10. Subsequently, deprotection was carried out according to the method used for the preparation of Compound T22-1-1 and Compound T22-1-2 to obtain the compounds described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 24 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                  995 
                 GT6-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid phenylamide 
                 A 
                 1.79 
                 501.0 
                 A9-10 
               
               
                   
               
               
                  996 
                 GT6-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid dimethylamide 
                 D 
                 1.33 
                 453.0 
                 A9-10 
               
               
                   
               
               
                  997 
                 GT6-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid 2- hydroxy-ethyl ester 
                 A 
                 1.40 
                 470.0 
                 A9-10 
               
               
                   
               
               
                  998 
                 GT6-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid butylamide 
                 D 
                 1.55 
                 481.0 
                 A9-10 
               
               
                   
               
               
                  999 
                 GT6-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid (2-methoxy-ethyl)-amide 
                 D 
                 1.30 
                 483.0 
                 A9-10 
               
               
                   
               
               
                 1000 
                 GT6-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid methylamide 
                 D 
                 1.24 
                 439.0 
                 A9-10 
               
               
                   
               
               
                 1001 
                 GT6-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid benzylamide 
                 D 
                 1.58 
                 515.0 
                 A9-10 
               
               
                   
               
               
                 1002 
                 GT6-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid amide 
                 D 
                 1.18 
                 425.0 
                 A9-10 
               
               
                   
               
               
                 1003 
                 GT6-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihyrdo-5H-benzo[b]carbazole- 3-carboxylic acid pyridin-4ylamide 
                 D 
                 1.40 
                 502.0 
                 A9-10 
               
               
                   
               
               
                 1004 
                 GT6-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid 
                 D 
                 1.01 
                 426.0 
                 E2-28 
               
               
                   
               
               
                 1005 
                 GT6-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid pyridin-2-ylamide 
                 D 
                 1.52 
                 502.0 
                 A9-10 
               
               
                   
               
               
                 1006 
                 GT6-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carboxylic acid pyridin-3-ylamide 
                 D 
                 1.34 
                 502.0 
                 A9-10 
               
               
                   
               
               
                 1007 
                 GT6-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-11-oxo-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b]carbazole- 3-carbolic acid phenethyl-amide 
                 D 
                 1.67 
                 529.0 
                 A9-10 
               
               
                   
               
               
                 1008 
                 GT6-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-[6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4-trihydroxy- butoxy)-6,11-dihydro- 5H-benzo[b]carbazole-3- carbonyl]- benzenesulfonamide 
                 D 
                 1.23 
                 565.0 
                 A9-10 
               
               
                   
               
            
           
         
       
     
     To the compounds described in the following Table 25, a hydroxyl group was introduced from Compound T17-3 according to the method described in JACS 2006, Vol. 128, page 10964. Subsequently, deprotection was carried out according to the method used for Compound A7-14-2 and Compound T22-2 to obtain the compounds shown below. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                   
                 Reten- 
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 HPLC 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1009 
                 GT7-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxyl-3- hydroxy-6,6-dimethyl-5,6-dihydro- benzo[b]carbazol-11-one 
                 B 
                 2.59 
                 368.4 
               
               
                   
               
               
                 1010 
                 GT7-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy-3- hydroxy-5,6,6-trimethyl-5,6-dihydro- benzo[b]carbazol-11-one 
                 C 
                 1.90 
                 382.4 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 26 were prepared by alkylation according to the method used for the preparation of Compound A7-1 from Compound GT7-1 or Compound GT7-2, or by carbamation according to the method used for the preparation of A9-1. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 26 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                 HPLC 
                 Reten- 
                   
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 Condi- 
                 tion 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 tion 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 1011 
                 GT8-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)- 3-ethoxy-5,6,6-trimethyl-5,6- dihydro-benzo[b]carbazol-11- one 
                 C 
                 2.43 
                 410.5 
                 A7-1 
               
               
                   
               
               
                 1012 
                 GT8-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)- 3-ethoxy-6,6-dimethyl-5,6- dihydro-benzo[b]carbazol-11- one 
                 C 
                 2.30 
                 396.5 
                 A7-1 
               
               
                   
               
               
                 1013 
                 GT8-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)- 5,6,6-trimethyl-3-(oxetan-3- yloxy)-5,6-dihydro-benzo[b] carbazol-11-one 
                 B 
                 1.72 
                 438.5 
                 A7-1 
               
               
                   
               
               
                 1014 
                 GT8-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Phenyl-carbamic acid 8-((R)- 2,3-dihydroxy-propoxy)- 6,6-dimethyl- 11-oxo-6,11-dihydro-5H- benzo[b]carbazol-3-yl ester 
                 B 
                 4.23 
                 487.0 
                 A9-1 
               
               
                   
               
            
           
         
       
     
     Example 1015 
     Compound GT9-1 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-(2H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (20.0 mg, 0.048 mmol), ammonium chloride (1.28 mg, 0.024 mmol) and NaN 3  (6.24 mg, 0.096 mmol) were dissolved in DMF, and the mixture was stirred at 120° C. for 14 hrs. NaN 3  (6.24 mg, 0.096 mmol) was further added to the mixture, which was then stirred at 120° C. for 30 hrs. The reaction solution was added with 1 N aqueous solution of hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resultant solid obtained after concentration was washed with hexane:ethyl acetate=1:1 to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-(2H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one as a white solid. 
     The product was suspended in MeOH (1.0 ml), added with 1 N aqueous solution of hydrochloric acid, and then stirred at 60° C. for 1 hr and 30 min. After cooling to room temperature, the reaction solution was concentrated under reduced pressure, and the resulting solid was washed with DCM to obtain the title compound as a pale yellow solid (13.4 mg, 66.3%). 
     LCMS: m/z 420 [M+H] +   
     Example 1016 
     Compound GT9-2 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-thiophen-3-yl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (20.0 mg, 0.043 mmol), thiophene-3-boronic acid (10.9 mg, 0.085 mmol), K 3 PO 4  (40 mg) and Pd (PPh 3 ) 4  (9.9 mg, 0.0086 mmol) were dissolved in DMA(0.8 ml) and water (0.2 ml), and stirred at 140° C. for 10 min under microwave irradiation. The reaction solution was diluted with ethyl acetate and washed with saturated brine. The organic layer was concentrated under reduced pressure, and the resulting residues were purified by column chromatography (hexane/ethyl acetate) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-thiophen-3-yl-5,6-dihydro-benzo[b]carbazol-11-one. 
     This product was suspended in MeOH (1.0 ml), added with 1 N hydrochloric acid, and then stirred at 60° C. for 1 hr and 30 min. The reaction solution was concentrated under reduced pressure, and the resulting solid was washed with DCM to obtain the title compound as a yellow solid (12.6 mg, 67.1%). 
     LCMS: m/z 434 [M+H] +   
     Using the combination of Compound T18-1 and corresponding boronic acid or the combination of (S)-8-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-6,6-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[b]carbazol-11 (6H)-one and corresponding bromide, the reaction was carried out in the same manner as Compound GT9-2 to obtain the compounds of the following Table 27. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 27 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                   
                 Reten- 
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 HPLC 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1017 
                 GT9-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-3-thiophen-2-yl-5,6-dihydro- benzo[b]carbazol-11-one 
                 B 
                 4.59 
                 494.0 
               
               
                   
               
               
                 1018 
                 GT9-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-3-(1H-pyrazol-4-yl)-5,6 dihydro-benzo[b]carbazol-11-one 
                 B 
                 4.04 
                 418.0 
               
               
                   
               
               
                 1019 
                 GT9-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-3-(2H-pyrazol-3-yl)-5,6- dihydro-benzo[b]carbazol-11-one 
                 A 
                 1.51 
                 418.0 
               
               
                   
               
               
                 1020 
                 GT9-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-3-thiazol-5-yl-5,6-dihydro- benzo[b]carbazol-11-one 
                 F 
                 1.97 
                 435.0 
               
               
                   
               
               
                 1021 
                 GT9-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-3-(3H- imidazol-4-yl)-6,6-dimethyl-5,6- dihydro-benzo[b]carbazol-11-one 
                 H 
                 2.91 
                 418.0 
               
               
                   
               
            
           
         
       
     
     Example 1022 
     Compound GT10-1 
     8-((2R,3R)-2,3,4-Trihydroxybutoxy)-2′,3′,5′,6′-tetrahydrospiro[benzo[b]carbazole-6,4′-pyran]-11(5H)-one 
     
       
         
         
             
             
         
       
     
     Preparation was carried out in the same manner as Compound N6-1-2. 
     LCMS: m/z 434 [M+H] +   
     HPLC retention time: 1.56 min (analysis condition A) 
     The compounds described in the following Table 28—were synthesized according to the method shown below. Specifically, by using the method for the preparation of Compound Z10, Z11, Z12 and Z13, 8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared from Compound A2 and bromophenol. To the resulting compound, a side chain or a synthetic equivalent thereof was introduced according to Mitsunobu reaction that is used for the preparation of Compound A7-1 or the method that is used for A7-17, etc. After that, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 28 
               
               
                   
               
               
                 Exam- 
                   
                   
                   
                   
                 Reten- 
                   
               
               
                 ple 
                 Comp. 
                   
                   
                 HPLC 
                 tion 
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1023 
                 GT11-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-5-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d]furan- 8-yloxy)-4-hydroxy-pentanoic acid 
                 H 
                 5.37 
                 395.0 
               
               
                   
               
               
                 1024 
                 GT11-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (R)-5-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d]furan- 8-yloxymethyl)-pyrrolidin-2-one 
                 H 
                 5.50 
                 376.0 
               
               
                   
               
               
                 1025 
                 GT11-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(3-Hydroxy-propoxy)-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d]furan-11- one 
                 H 
                 5.97 
                 337.0 
               
               
                   
               
               
                 1026 
                 GT11-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(3-Ethyl-3-hydroxy-pentyloxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 9.29 
                 393.0 
               
               
                   
               
               
                 1027 
                 GT11-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (6,6-Dimethyl-11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d]furan-8- yloxy)-acetic acid 
                 H 
                 5.65 
                 336.0 
               
               
                   
               
               
                 1028 
                 GT11-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d] furan-8-yloxy)-butyric acid 
                 H 
                 6.15 
                 365.0 
               
               
                   
               
               
                 1029 
                 GT11-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 5-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d] furan-8-yloxy)-pentanoic acid 
                 H 
                 6.44 
                 379.0 
               
               
                   
               
               
                 1030 
                 GT11-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d] furan-8-yloxy)-hexanoic acid 
                 H 
                 6.77 
                 393.0 
               
               
                   
               
               
                 1031 
                 GT11-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo-6,11-di- hydro-benzo[b]naphtho[2,3-d]furan- 8-yloxy)-N,N-diethyl-acetamide 
                 H 
                 6.39 
                 392.0 
               
               
                   
               
               
                 1032 
                 GT11-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(2-morpholin-4-yl- ethoxy)-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 4.45 
                 392.0 
               
               
                   
               
               
                 1033 
                 GT11-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Dimethylamino-ethoxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 4.59 
                 350.0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 29 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1034  
                 GT11-12  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((S)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 F 
                 2.40 
                 353.0 
               
               
                   
               
               
                 1035  
                 GT11-13  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 5.07 
                 353.0 
               
               
                   
               
               
                 1036  
                 GT11-14  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(2-pyrrolidin-1-yl- ethoxy)-6H-benzo[b]naphtho[2,3- d]furan-11-one 
                 C 
                 3.03 
                 375.9 
               
               
                   
               
               
                 1037  
                 GT11-15  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(2-piperidin-1-yl- ethoxy)-6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 C 
                 3.15 
                 389.9 
               
               
                   
               
               
                 1038  
                 GT11-16  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(3-Dimethylamino-propoxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 C 
                 3.30 
                 364.2 
               
               
                   
               
               
                 1039  
                 GT11-17  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Azepan-1-yl-ethoxy)-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d]furan-11- one  
                 F 
                 2.35 
                 404.3 
               
               
                   
               
               
                 1040  
                 GT11-18  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (6,6-Dimethyl-11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d]furan-8-yloxy)- acetic acid methyl ester  
                 D 
                 2.38 
                 351.0 
               
               
                   
               
               
                 1041  
                 GT11-19  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d]furan-8-yloxy)- N-(2-morpholin-4-yl-ethyl)-acetamide  
                 D 
                 2.03 
                 450.0 
               
               
                   
               
               
                 1042  
                 GT11-20  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(2-piperazin-1-yl- ethoxy)-6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 C 
                 2.81 
                 391.2 
               
               
                   
               
               
                 1043  
                 GT11-21  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(4-Methanesulfonyl-piperazin-1- yl)-ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 F 
                 2.21 
                 469.1 
               
               
                   
               
               
                 1044  
                 GT11-22  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d]furan-8-yloxy)- acetamide  
                 D 
                 1.95 
                 336.0 
               
               
                   
               
               
                 1045  
                 GT11-23  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-[2-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d]furan- 8-yloxy)-ethyl]-piperazine-1-carboxylic acidamide 
                 F 
                 2.04 
                 434.0 
               
               
                   
               
               
                 1046  
                 GT11-24  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-(2,3-Dihydroxy-propyl)-2-(6,6- dimethyl-11-oxo-6,11-dihydro- benzo[b]naptho[2,3-d]furan-8-yloxy)- acetamide 
                 D 
                 1.82 
                 410.0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 30 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1047  
                 GT11-25  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(4-Acetyl-piperazin-1-yl)- ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 2.10 
                 433.1 
               
               
                   
               
               
                 1048  
                 GT11-26  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-[2-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho[2,3-d] furan-8-yloxy)-acetyl]- piperazine-1-carboxylic acid tert-butyl ester  
                 D 
                 2.53 
                 505.0 
               
               
                   
               
               
                 1049  
                 GT11-27  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(2-Hydroxy-ethoxy)- ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho[2,3- d]furan-11-one  
                 H 
                 5.62 
                 367.0 
               
               
                   
               
               
                 1050  
                 GT11-28  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[2-(2-Hydroxy-ethoxy)- ethoxy]-ethoxy}-6,6- dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 H 
                 5.64 
                 411.0 
               
               
                   
               
               
                 1051  
                 GT11-29  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Imidazol-1-yl-ethoxy)-6,6- dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one  
                 F 
                 2.05 
                 373.1 
               
               
                   
               
               
                 1052  
                 GT11-30  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-(2-pyridin-4-yl-ethyl)- acetamide 
                 D 
                 2.10 
                 441.0 
               
               
                   
               
               
                 1053  
                 GT11-31  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-(2-Dimethylamino-ethyl)- 2-(6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- acetamide  
                 D 
                 2.01 
                 407.0 
               
               
                   
               
               
                 1054  
                 GT11-32  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-[2-(2-hydroxy-ethoxy)- ethyl]-acetamide  
                 D 
                 1.88 
                 424.0 
               
               
                   
               
               
                 1055  
                 GT11-33  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-[2-(4-methyl- piperazin-1-yl)-ethoxy]- 6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 
                   
                 
                 405.2 
               
               
                   
               
               
                 1056  
                 GT11-34  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-((2R,3R)-2,3,4- trihydroxy-butoxy)-6H- benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 2.21 
                 383.0 
               
               
                   
               
               
                 1057  
                 GT11-35  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2-Hydroxy-3- piperidin-1-yl-propoxy)-6,6- dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 2.25 
                 420.0 
               
               
                   
               
               
                 1058  
                 GT11-36  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(2-oxo-2- piperazin-1-yl-ethoxy)- 6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 D 
                 1.92 
                 405.0 
               
               
                   
               
               
                 1059  
                 GT11-37  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[4-(2-Hydroxy-acetyl)- piperazin-1- yl]-ethoxy}-6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 2.06 
                 449.1 
               
               
                   
               
               
                 1060  
                 GT11-38  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((S)-2-Hydroxy-3-piperidin-1-yl- propoxy)-6,6-dimethyl-6H- benzo[b]naptho[2,3-d]furan-11-one 
                 F 
                 2.24 
                 420.0 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 31 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1061  
                 GT11-39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-((R)-2,3-Dihydroxy- propylamino)- ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one  
                 H 
                 4.18 
                 
                   
                 
               
               
                   
               
               
                 1062  
                 GT11-40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((S)-4,5-Dihydroxy- pentyloxy)-6,6- dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one  
                 F 
                 2.56 
                 381.0 
               
               
                   
               
               
                 1063  
                 GT11-41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-[2-(6,6-Dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho [2,3-d]furan- 8-yloxy)-ethyl]- piperazin-2-one  
                 F 
                 2.06 
                 405.0 
               
               
                   
               
               
                 1064  
                 GT11-42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- N-piperidin-4-yl-acetamide  
                 D 
                 
                   
                 
                 419.0 
               
               
                   
               
               
                 1065  
                 GT11-43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-{2-[Bis-(2-hydroxy- ethyl)-amino]- ethyl}-2-(6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)-acetamide  
                 D 
                 1.83 
                 467.0 
               
               
                   
               
               
                 1066  
                 GT11-44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-(3-Dimethylamino-propyl)- 2-(6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- acetamide  
                 D 
                 2.08 
                 422.0 
               
               
                   
               
               
                 1067  
                 GT11-45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 N-(2-Diethylamino-ethyl)- 2-(6,6-dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- acetamide  
                 D 
                 2.10 
                 
                   
                 
               
               
                   
               
               
                 1068  
                 GT11-46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(pyrimidin- 2-yloxy)-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 H 
                 6.35 
                 357.0 
               
               
                   
               
               
                 1069  
                 GT11-47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Ethylamino-ethoxy)- 6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 2.15 
                 350.0 
               
               
                   
               
               
                 1070  
                 GT11-48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)-ethyl]- piperazin-2-one  
                 H 
                 4.42 
                 405.0 
               
               
                   
               
               
                 1071  
                 GT11-49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b] naphtho[2,3-d]furan- 8-yloxy)-ethyl]-1- methyl-piperazin-2-one  
                 H 
                 4.33 
                 419.0 
               
               
                   
               
               
                 1072  
                 GT11-50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-(2-piperazin-1-yl-ethyl)- acetamide  
                 A 
                 3.99 
                 448.0 
               
               
                   
               
               
                 1073  
                 GT11-51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Dimethylamino- N-[2-(6,6-dimethyl- 11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- ethyl]-acetamide 
                 D 
                 2.13 
                 408.0 
               
               
                   
               
               
                 1074  
                 GT11-52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naptho [2,3-d]furan-8-yloxy)-ethyl]- 1,1-dimethyl-3-oxo- piperazin-1-ium; chloride 
                 H 
                 4.47 
                 
                   
                 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 32 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1075 
                 GT11-53  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[4-(2-Hydroxy-ethyl)- piperazin-1-yl]-ethoxy}-6,6- dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one  
                 A 
                 1.75 
                 435.0 
               
               
                   
               
               
                 1076 
                 GT11-54  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)-ethyl]- 4-methyl-piperazin-2-one  
                 B 
                 4.09 
                 419.0 
               
               
                   
               
               
                 1077 
                 GT11-55  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(3-piperazin-1-yl- propoxy)-6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 A 
                 1.75 
                 405.0 
               
               
                   
               
               
                 1078 
                 GT11-56  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[4-((S)-2,3-Dihydroxy- propyl)-piperazin-1-yl]-ethoxy}- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 A 
                 1.72 
                 465.0 
               
               
                   
               
               
                 1079 
                 GT11-57  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(2-Hydroxy-1,1- dimethyl-ethylamino)-ethoxy]- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one  
                 
                   
                 
                 2.57 
                 394.0 
               
               
                   
               
               
                 1080 
                 GT11-58  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[Bis-(2-hydroxy-ethyl)- amino]-ethoxy}-6,6- dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 
                   
                 
                 2.77 
                 410.0 
               
               
                   
               
               
                 1081 
                 GT11-59  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(3-Hydroxy-piperidin-1-yl)- ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho[2,3- d]furan-11-one  
                 
                   
                 
                 2.88 
                 406.0 
               
               
                   
               
               
                 1082 
                 GT11-60  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(2-Hydroxymethyl- pyrrolidin-1-yl)- ethoxy]-6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one  
                 
                   
                 
                 2.82 
                 406.0 
               
               
                   
               
               
                 1083 
                 GT11-61  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-{2-[Ethyl-(2-hydroxy- ethyl)-amino]- ethoxy}-6,6-dimethyl-6H- benzol[b]naphtho [2,3-d]furan-11-one  
                 
                   
                 
                 2.85 
                 394.0 
               
               
                   
               
               
                 1084 
                 GT11-62  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(3-methyl- oxetan-3- ylmethoxy)-6H- benzo[b]naphtho[2,3- d]furan-11-one  
                 
                   
                 
                 3.03 
                 363.0 
               
               
                   
               
               
                 1085 
                 GT11-63  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-[2-(1-Hydroxymethyl- cyclopentylamino)-ethoxy]- 6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 
                   
                 
                 2.72 
                 420.0 
               
               
                   
               
               
                 1086 
                 GT11-64  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(4-Hydroxy-pyrrolidin- 2-ylmethoxy)-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one  
                 Y 
                 2.96 
                 378.0 
               
               
                   
               
               
                 1087 
                 GT11-65  
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(piperidin- 3-yloxy)-6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 Y 
                 3.03 
                 362.0 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     The compounds described in the following Table 33 were synthesized according to the method shown below. From Compound A2 and 2-bromophenol having a fluorine atom at corresponding position, 8-methoxy-6H-benzo[b]naphtho[2,3-d]furan-11-one having a fluorine atom at corresponding position (Compound GT12-1, GT12-2, GT12-5 and GT12-7) was prepared according to the method used for the preparation of Compound Z10, Z11 and Z12. Further, demethylation was carried out according to the method used for the preparation of Compound A6 to obtain 8-hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one which has a fluorine atom at corresponding position. Thereafter, according to Mitsunobu reaction used for the preparation of Compound A7-1 or the alkylation method used for the preparation of Compound A7-17, a corresponding side chain was introduced and, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 33 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1088 
                 GT12-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Fluoro-8-methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 A 
                 3.02 
                 311.0 
               
               
                   
               
               
                 1089 
                 GT12-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 4-Fluoro-8-methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 A 
                 3.00 
                 311.0 
               
               
                   
               
               
                 1090 
                 GT12-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino-ethoxy)-3-fluoro- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 B 
                 4.48 
                 396.0 
               
               
                   
               
               
                 1091 
                 GT12-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Fluoro-6,6-dimethyl-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 H 
                 4.91 
                 401.4 
               
               
                   
               
               
                 1092 
                 GT12-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-Fluoro-8-methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 
                   
                 
                 3.01 
                 311.0 
               
               
                   
               
               
                 1093 
                 GT12-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino-ethoxy)-2-fluoro- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 
                   
                 
                 2.09 
                 395.0 
               
               
                   
               
               
                 1094 
                 GT12-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1-Fluoro-8-methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 B 
                 6.26 
                 311.0 
               
               
                   
               
               
                 1095 
                 GT12-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-2- fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 C 
                 2.22 
                 371.0 
               
               
                   
               
               
                 1096 
                 GT12-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino-ethoxy)-1-fluoro- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 B 
                 4.20 
                 396.0 
               
               
                   
               
               
                 1097 
                 GT12-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-3- fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 B 
                 
                   
                 
                 371.0 
               
               
                   
               
               
                 1098 
                 GT12-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-4- fluoro-6,6-dimethyl-6H- benzo[d]naphtho[2,3-d]furan-11-one  
                 D 
                 1.80 
                 371.0 
               
               
                   
               
               
                 1099 
                 GT12-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-propoxy)-1- fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one 
                 D 
                 1.85 
                 371.0 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     The compounds described in the following Table 34 were synthesized according to the method shown below. 8-Hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was transformed into trifluoromethanesulfonic acid ester according to the method used for the preparation of Compound B1. Subsequently, by carrying out the method used for the preparation of Compound B2-1 or Compound B2-18, Compound GT13-1, Compound GT13-2 and Compound GT13-3 were prepared. Compound GT13-3 was oxidized according to the method used for the preparation of Compound B3-8 to prepare Compound 13-4. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 34 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 1100 
                 GT13-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-morpholin-4-yl-6H- benzo[b]naphtho[2,3-d]furan-11-one  
                 F 
                 3.04 
                 348.2 
                 B1, B2-1 
               
               
                   
               
               
                 1101 
                 GT13-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-8-(4-methyl-piperazin- 1-yl)-6H-benzo[b]naphtho[2,3-d] furan-11-one  
                 F 
                 2.13 
                 361.3 
                 B1, B2-1 
               
               
                   
               
               
                 1102 
                 GT13-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diisopropylamino-ethyl- sulfanyl)-6,6-dimethyl-6H-benzo [b]naphtho[2,3-d]furan-11-one  
                 C 
                 3.45 
                 422.0 
                 
                   
                 
               
               
                   
               
               
                 1103 
                 GT13-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diisopropylamino- ethanesulfonyl)-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one 
                 C 
                 3.23 
                 454.0 
                 
                   
                 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     The compounds described in the following Table 35 were synthesized according to the method shown below. Specifically, a side chain was introduced to Compound Z13 to prepare Compound GT13-5 according to the method that is used for the preparation of Compound A7-17. Further Compound GT13-5 or trifluoromethanesulfonic acid ester of Compound Z14 was hydrolyzed to prepare Compound GT13-6 and Compound GT13-7 according to the method used for the preparation of Compound T20. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 35 
               
               
                   
               
               
                 Example 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
                   
               
               
                 No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
             
            
               
                 1104 
                 GT13-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Trifluoro-methanesulfonic acid 8-(2-diethylamino-ethoxy)- 6,6-dimethyl-11-oxo-6,11- dihydro-benzo[b]naphtho [2,3-d]furan-3-yl ester  
                 H 
                 5.37 
                 526.0 
                 A7-17 
               
               
                   
               
               
                 1105 
                 GT13-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino-ethoxy)- 3-hydroxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3- d]furan-11-one 
                 B 
                 3.40 
                 384.0 
                 T20 
               
               
                   
               
               
                 1106 
                 GT13-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Hydroxy-6,6-dimethyl- 8-((2R,3R)-2,3,4-trihydroxy- butoxy)-6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 1.87 
                 399.0 
                 T20 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 36 were prepared by subjecting Compound GT13-6 or GT13-7 to Mitsunobu reaction that is used for the preparation of Compound A7-1 to introduce a corresponding side chain or a synthetic equivalent. After that, by carrying out deprotection, if necessary, the compounds listed below were prepared. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 36 
               
               
                   
               
               
                   
                   
                   
                   
                 HPLC 
                 Re- 
                   
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 Con- 
                 tention 
                   
                 Me- 
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 dition 
                 Time 
                 m/z 
                 thod 
               
               
                   
               
             
            
               
                 1107 
                 GT13-8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-3-methoxy- 6,6-dimethyl-6H- benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 4.72 
                 408.0 
                 A7-1 
               
               
                   
               
               
                 1108 
                 GT13-9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Methoxy-6,6- dimethyl-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6H -benzo[b] naphtho[2,3-d] furan-11-one 
                 B 
                 4.23 
                 413.2 
                 A7-1 
               
               
                   
               
               
                 1109 
                 GT13-10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-3-ethoxy- 6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan- 11-one 
                 H 
                 5.10 
                 422.0 
                 A7-1 
               
               
                   
               
               
                 1110 
                 GT13-11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-Diethylamino- ethoxy)-6,6-dimethyl- 3-propoxy-6H-benzo [b]naphtho[2,3-d] furan-11-one  
                 H 
                 5.63 
                 436.0 
                 A7-1 
               
               
                   
               
               
                 1111 
                 GT13-12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-Hydroxy- ethoxy)-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one  
                 F 
                 1.83 
                 443.0 
                 A7-1 
               
               
                   
               
               
                 1112 
                 GT13-13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(3-Hydroxy- propoxy)-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 1.94 
                 457.0 
                 A7-1 
               
               
                   
               
               
                 1113 
                 GT13-14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Hydroxy- butoxy)-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 2.01 
                 471.0 
                 A7-1 
               
               
                   
               
               
                 1114 
                 GT13-15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Isopropoxy-6,6- dimethyl-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6H-benzo [b]naphtho[2,3-d] furan-11-one 
                 H 
                 5.40 
                 441.0 
                 A7-1 
               
               
                   
               
               
                 1115 
                 GT13-16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-Methoxy- ethoxy)-6,6- dimethyl-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6H-benzo [b]naphtho[2,3-d] furan-11-one 
                 F 
                    .17 
                 457.0 
                 A7-1 
               
               
                   
               
               
                 1116 
                 GT13-17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(3-Methoxy-pro- poxy)-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 2.34 
                 471.0 
                 A7-1 
               
               
                   
               
               
                 1117 
                 GT13-18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(4-Methoxy- butoxy)-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 2.45 
                 485.0 
                 A7-1 
               
               
                   
               
               
                 1118 
                 GT13-19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-((S)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b] naphtho[2,3-d] furan-11-one 
                 F 
                 1.69 
                 473.0 
                 A7-1 A7- 14-1 
               
               
                   
               
               
                 1119 
                 GT13-20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 F 
                 1.69 
                 473.0 
                 A7-1 A7- 14-1 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     The compounds described in the following Table 37 were prepared from Compound GT13-7 according to carbamation that is used for the preparation of Compound A9-1. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 37 
               
               
                   
               
               
                   
                   
                   
                   
                 HPLC 
                 Re- 
                   
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 Con- 
                 tention 
                   
                 Me- 
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 dition 
                 Time 
                 m/z 
                 thod 
               
               
                   
               
             
            
               
                 1120 
                 GT13-21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (4-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester 
                 B 
                 4.34 
                 548.2 
                 
                   
                 
               
               
                   
               
               
                 1121 
                 GT13-22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (3-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro-benzo [b]naphtho[2,3-d] furan-3-yl ester 
                 B 
                 4.69 
                 548.2 
                 
                   
                 
               
               
                   
               
               
                 1122 
                 GT13-23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (2-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro-benzo [b]naphtho[2,3-d] furan-3-yl ester 
                 B 
                 
                   
                 
                 548.3 
                 
                   
                 
               
               
                   
               
               
                 1123 
                 GT13-24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Phenyl-carbamic acid  6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy- butoxy)-6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester  
                 B 
                 4.67 
                 518.2 
                 
                   
                 
               
               
                   
               
               
                 1124 
                 GT13-25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Cyclohexyl-carbamic  acid 6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro-benzo [b]naphtho[2,3-d] furan-3-yl ester 
                 B 
                 4.94 
                 524.2 
                 
                   
                 
               
               
                   
               
               
                 1125 
                 GT13-26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Benzyl-carbamic  acid 6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro-benzo [b]naphtho[2,3-d] furan-3-yl ester 
                 A 
                 2.08 
                 532.3 
                 
                   
                 
               
               
                   
               
               
                 1126 
                 GT13-27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 Methyl-phenyl-carbamic  acid 6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-benzo[b]naphtho [2,3-d]furan-3-ylester 
                 B 
                 4.88 
                 532.3 
                 
                   
                 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     The compounds described in the following Table 38 were prepared from corresponding intermediates by alkylation and carbamation based on the method described in the Table. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 38 
               
               
                   
               
               
                   
                   
                   
                   
                 HPLC 
                 Re- 
                   
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 Con- 
                 tention 
                   
                 Me- 
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 dition 
                 Time 
                 m/z 
                 thod 
               
               
                   
               
             
            
               
                 1127 
                 GT13-28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-(2-Diethylamino- ethoxy)-8-methoxy- 6,6-dimethyl-6H- benzo[b]naphtho[2,3- d]furan-11-one 
                 H 
                 4.65 
                 408.0 
                 A7-17 
               
               
                   
               
               
                 1128 
                 GT13-29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2-[8-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-11-oxo- 6,11-dihydro-benzo [b]naphtho[2,3-d] furan-3-yloxy]- N-phenyl-acetamide  
                 B 
                 4.70 
                 502.0 
                 A7-17 A8-1 T13- 3 
               
               
                   
               
               
                 1129 
                 GT13-30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (4-tert-Butyl-phenyl)- carbamic acid 8- ((R)-2,3-dihydroxy- propoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-3-yl ester 
                 B 
                 6.19 
                 544.3 
                 
                   
                 
               
               
                   
               
               
                 1130 
                 GT13-31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (2-tert-Butyl-phenyl)- carbamic acid 8-((R)- 2,3-dihydroxy-propoxy)- 6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b] naphtho[2,3-d]furan- 3-yl ester 
                 B 
                 5.74 
                 544.3 
                 
                   
                 
               
               
                   
               
               
                 1131 
                 GT13-32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 (5-tert-Butyl-2- methoxy-phenyl)- carbamic acid 8-((R)- 2,3-dihydroxy- propoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- benzo[b]naphtho [2,3-d]furan- 3-yl ester 
                 B 
                 6.52 
                 574.3 
                 
                   
                 
               
               
                   
               
               
                 1132 
                 GT13-33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 6,6-Dimethyl-3- (pyrimidin-2-yloxy)- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 H 
                 4.14 
                 477.0 
                 A7-17 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     Example 1133 
     Compound GT14-1 
     3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[f]pyrido[4,3-b]indol-11-one 
     
       
         
         
             
             
         
       
     
     Compound BZ2-2 was demethylated according to the method used for the preparation of Compound A6, and subsequently introduced with a substituent group and deprotected according to the method used for the preparation of Compound A7-14-1 and A7-14-2. 
     LCMS: m/z 386 [M+H] +   
     HPLC retention time: 3.02 min (analysis condition B) 
     Example 1134 
     Compound GT15-1 
     2-Iodo-3-(4-methoxy-benzyloxy)-pyridine 
     
       
         
         
             
             
         
       
     
     2-Iodo-pyridin-3-ol (50 mg, 0.226 mmol), K 2 CO 3  (62 mg, 0.452 mmol) and DMF (2 ml) were added with para-methoxybenzyl chloride (46 μL, 0.339 mmol), and the mixture was stirred overnight at 45° C. The resultant was added with water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and the resulting residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (21 mg, 27%). 
     LCMS: m/z 342 [M+H] +   
     HPLC retention time: 3.44 min (analysis condition Y) 
     Example 1135 
     Compound GT15-2 
     7-Methoxy-3-[3-(4-methoxy-benzyloxy)-pyridin-2-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     Toluene (0.5 ml) was added to 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 36 mg), 2-iodo-3-(4-methoxy-benzyloxy)-pyridine (Compound GT15-1, 50 mg), sodium t-butoxide (35.3 mg), Pd 2 dba3 (13.5 mg) and Xantphos (17 mg), and the mixture was stirred and heated at 80° C. for 2.5 hrs under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and subjected to Celite filtration. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (27 mg, 44%). 
     LCMS: m/z 419 [M+H] +   
     HPLC retention time: 3.31 min (analysis condition Y) 
     Example 1136 
     Compound GT15-3 
     8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-4-aza-benzo[b]fluorene 
     
       
         
         
             
             
         
       
     
     To the mixture of 7-methoxy-3-[3-(4-methoxy-benzyloxy)-pyridin-2-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-2, 21 mg) and ethyl acetate (0.8 ml), sulfuric acid (0.2 ml) was added. The mixture was stirred and heated at 70° C. for 5 hrs. After cooling, the reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (7 mg, 50%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 2.71 min (analysis condition Y) 
     Example 1137 
     Compound GT15-4 
     8-Methoxy-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-4-aza-benzo[b]fluorene (Compound GT15-3, 22 mg) was dissolved in MeCN (0.26 ml) and water (0.13 ml), added with sodium chlorite (14 mg) and N-hydroxyphthalimide (2.6 mg), and the mixture was stirred at 40° C. for 1 hr. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (16 mg, 70%). 
     LCMS: m/z 294 [M+H] +   
     HPLC retention time: 2.85 min (analysis condition Y) 
     Example 1138 
     Compound GT15-5 
     8-Hydroxy-10,10-dimethyl-10H-1I-oxa-4-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Mixture of 8-methoxy-10,10-dimethyl-10H-1I-oxa-4-aza-benzo[b]fluoren-5-one (Compound GT15-4, 25 mg) and pyridine hydrochloric acid salt (492 mg) was stirred and heated at 178° C. overnight. The reaction mixture was cooled, and added with water. The mixture was neutralized with saturated aqueous solution of sodium bicarbonate and extracted with DCM. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (DCM/MeOH) to obtain the title compound (13 mg, 54%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition Y) 
     Example 1139 
     Compound GT15-6 
     8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound A7-1, the title compound was synthesized from Compound GT15-5 and Compound T22-0 (29 mg, 50%). 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 3.64 min (analysis condition Y) 
     Example 1140 
     Compound GT15-7 
     10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-4-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     To the mixture of 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one (Compound GT15-6, 27 mg), MeOH (0.1 ml) and THF (0.3 ml), 0.5 N sulfuric acid (0.1 ml) was added, and the mixture was stirred and heated at 55 to 60° C. for 4 hrs. The reaction mixture was neutralized with saturated aqueous solution of sodium bicarbonate. The resulting solid was filtered and washed with diethyl ether. The filtrate was extracted with the mixture solution of DCM and MeOH (DCM:MeOH=10:1). The organic layer was washed with saturated brine, and dried over magnesium sulfate. The filtered solid and the residues obtained after concentration under reduced pressure were combined and purified by silica gel column (DCM/MeOH) to obtain the title compound (5.4 mg, 28%). 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 2.02 min (analysis condition Y) 
     Example 1141 
     Compound GT15-8 
     7-Methoxy-3-(3-methoxymethoxy-pyridin-4-yl)-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 924 mg), 4-iodo-3-methoxymethoxy-pyridine (1 g), sodium t-butoxide (906 mg), Pd 2 dba3 (173 mg) and S-Phos (185 mg), toluene (19 ml) was added, and the mixture was stirred and heated at 70° C. for 2 hrs under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and filtered through Celite. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (610 mg, 47%). 
     LCMS: m/z 342 [M+H] +   
     HPLC retention time: 2.60 min (analysis condition Y) 
     Example 1142 
     Compound GT15-9 
     3-(3-Hydroxy-pyridin-4-yl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     Mixture of 7-methoxy-3-(3-methoxymethoxy-pyridin-4-yl)-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-8, 430 mg) and 4 N hydrochloric acid dioxane solution (5 ml) was heated and stirred at room temperature for 1.5 hrs. The reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The resulting mixture was extracted with the mixture of DCM and MeOH (DCM:MeOH=9:1). The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/MeOH) to obtain the title compound (280 mg, 75%). 
     LCMS: m/z 298 [M+H] +   
     HPLC retention time: 2.41 min (analysis condition Y) 
     Example 1143 
     Compound GT15-10 
     8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-2-aza-benzo[b]fluorene 
     
       
         
         
             
             
         
       
     
     Mixture of 3-(3-hydroxy-pyridin-4-yl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-9, 270 mg) and methanesulfonic acid (1 ml) was stirred and heated at 110° C. for 0.5 hrs. After cooling, the reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The resulting mixture was extracted with the mixture of DCM and MeOH (DCM:MeOH=9: 1). The organic layer was concentrated under reduced pressure, and the resulting residues were purified by silica gel column (DCM/MeOH) to obtain the title compound (110 mg, 43%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 2.53 min (analysis condition Y) 
     Example 1144 
     Compound GT15-11 
     8-Methoxy-10,10-dimethyl-10H-1l-oxa-2-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-2-aza-benzo[b]fluorene (Compound GT15-10, 20 mg) was dissolved in acetonitrile (0.2 ml) and water (0.15 ml), added with sodium chlorite (16 mg) and N-hydroxyphthalimide (2.3 mg), and the mixture was stirred at 40° C. for 40 min. To the reaction mixture, ethyl acetate was added. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (12 mg, 57%). 
     LCMS: m/z 294 [M+H] +   
     HPLC retention time: 2.51 min (analysis condition Y) 
     Example 1145 
     Compound GT15-12 
     8-Hydroxy-10,10-dimethyl-10H-11-oxa-2-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     DCM (0.34 ml) solution of 8-methoxy-10,10-dimethyl-10H-11-oxa-2-aza-benzo[b]fluoren-5-one (Compound GT15-11, 10 mg) was cooled to −78° C., added with the DCM solution (0.17 ml) of 1.0 M BBr 3 , and the mixture was stirred at room temperature overnight. To the reaction mixture, water and saturated aqueous solution of sodium bicarbonate were added, and the solid produced therefrom was filtered off. The filtrate was extracted with the mixture solution of DCM and MeOH (DCM:MeOH=9:1). The organic layer was washed with saturated brine. The filtered solid and the residues obtained after concentration under reduced pressure were combined to obtain the title compound (9.5 mg, 99%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 2.50 min (analysis condition Y) 
     Example 1146 
     Compound GT15-13 
     8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-1l-oxa-2-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-12 and Compound T22-0 (38 mg, 66%). 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 3.55 min (analysis condition Y) 
     Example 1147 
     Compound GT15-14 
     10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-2-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-13 (2.1 mg, 84%). 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 1.70 min (analysis condition Y) 
     Example 1148 
     Compound GT15-15 
     3-Bromo-2-(4-methoxy-benzyloxy)-pyridine 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound G15-1, the title compound was prepared from 3-bromo-pyridin-2-ol (740 mg, 88%). 
     LCMS: m/z 295 [M+H] +   
     HPLC retention time: 2.86 min (analysis condition Y) 
     Example 1149 
     Compound GT15-16 
     7-Methoxy-3-[2-(4-methoxy-benzyloxy)-pyridin-3-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one 
     
       
         
         
             
             
         
       
     
     To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 845 mg), 3-bromo-2-(4-methoxy-benzyloxy)-pyridine (Compound GT15-15, 1.46 g), sodium t-butoxide (597 mg), palladium acetate (18.6 mg) and tri-tert-butylphosphine tetrafluoroboric acid (21 mg), toluene (10 ml) and THF (2 ml) were added and the mixture was stirred and heated at 90° C. for 2.5 hrs under nitrogen atmosphere. After cooling, the reaction mixture was added with saturated aqueous solution of ammonium chloride, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (140 mg, 8%). 
     LCMS: m/z 419 [M+H] +   
     HPLC retention time: 3.50 min (analysis condition Y) 
     Example 1150 
     Compound GT15-17 
     8-Methoxy-10,10-dimethyl-10H-11-oxa-1-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-3, the title compound was prepared from Compound GT15-16 (49 mg, 52%). 
     LCMS: m/z 294 [M+H] +   
     HPLC retention time: 3.39 min (analysis condition Y) 
     Example 1151 
     Compound GT15-18 
     8-Hydroxy-10,10-dimethyl-10H-11-oxa-1-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-5, the title compound was prepared from Compound GT15-17 (6.5 mg, 51%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 3.10 min (analysis condition Y) 
     Example 1152 
     Compound GT15-19 
     8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-1l-oxa-1-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-18 and Compound T22-0 (4.5 mg, 11%). 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 3.88 min (analysis condition Y) 
     Example 1153 
     Compound GT15-20 
     10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-1-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-19 (7.9 mg, 51%). 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 2.57 min (analysis condition Y) 
     Example 1154 
     Compound GT15-21 
     8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-3-aza-benzo[b]fluorene 
     
       
         
         
             
             
         
       
     
     To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.5 g), 3-bromo-4-chloro-pyridine (2 g), sodium t-butoxide (3 g), Pd 2 dba 3  (476 mg), and S-Phos (512 mg), toluene (20 ml) was added, and the mixture was stirred and heated at 100° C. overnight under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and filtered through Celite. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine. Thereafter, the organic layer was dried over sodium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (112 mg, 4%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 2.46 min (analysis condition Y) 
     Example 1155 
     Compound GT15-22 
     8-Methoxy-10,10-dimethyl-10H-11-oxa-3-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-3, the title compound was prepared from Compound GT15-21 (49 mg, 52%). 
     LCMS: m/z 294 [M+H] +   
     HPLC retention time: 2.30 min (analysis condition Y) 
     Example 1156 
     Compound GT15-23 
     8-Hydroxy-10,10-dimethyl-10H-11-oxa-3-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-12, the title compound was prepared from Compound GT15-22 (110 mg, 77%). 
     LCMS: m/z 280 [M+H] +   
     HPLC retention time: 1.95 min (analysis condition Y) 
     Example 1157 
     Compound GT15-24 
     8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-1l-oxa-3-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-23 and Compound T22-0 (38 mg, 49%). 
     LCMS: m/z 538 [M+H] +   
     HPLC retention time: 3.40 min (analysis condition Y) 
     Example 1158 
     Compound GT15-25 
     10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-3-aza-benzo[b]fluoren-5-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-24 (17 mg, 72%). 
     LCMS: m/z 384 [M+H] +   
     HPLC retention time: 1.48 min (analysis condition Y) 
     Example 1159 
     Compound GT16-1 
     2-(2-Bromo-4-methoxy-phenyl)-propan-2-ol 
     
       
         
         
             
             
         
       
     
     To the mixture of 1-(2-bromo-4-methoxyphenyl)-ethanone (300 mg) dissolved in THF solution (3 ml), MeMgBr (3 M THF solution, 0.52 ml) was added at 0° C. under nitrogen atmosphere. Then, the mixture was stirred at room temperature for 6 hrs. The reaction mixture was added with saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (220 mg, 69%). 
       1 H-NMR (CDCL 3 ) δ: 7.55 (1H, d), 7.14 (1H, d), 6.83 (1H, dd), 3.79 (3H, s), 2.72 (1H, s), 1.73 (6H, s) 
     Example 1160 
     Compound GT16-2 
     2-[1-(2-Bromo-4-methoxyphenyl)-1-methylethyl]benzofuran 
     
       
         
         
             
             
         
       
     
     Mixture comprising 2-(2-bromo-4-methoxyphenyl)-propan-2-ol (100 mg), 2,3-benzofuran (0.19 ml) and polyphosphoric acid (1 g) was stirred and heated at 90° C. for 30 min. The reaction mixture was added with water and extracted with DCM. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/hexane) to obtain the title compound (143 mg, 51%). 
       1 H-NMR (CDCL 3 ) δ: 7.4-7.5 (1H, m), 7.3-7.4 (2H, m), 7.1-7.25 (3H, m), 6.87 (1H, dd), 6.42 (1H, s) 3.79 (3H, s), 1.84 (6H, s) 
     Example 1161 
     Compound GT16-3 
     2-(1-Benzofuran-2-yl-1-methyl-ethyl)-5-methoxy-benzoic acid 
     
       
         
         
             
             
         
       
     
     To the mixture comprising 2-[1-(2-bromo-4-methoxyphenyl)-1-methylethyl]benzofuran (140 mg) and THF (2 ml), n-butyl lithium (2.5 M solution, 0.17 ml) was added at −78° C. under nitrogen atmosphere. The mixture was stirred for 20 min. The resulting reaction mixture was flushed with carbon dioxide gas for 15 min. Then, the reaction mixture was added with saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/MeOH) to obtain the title compound (68 mg, 54%). 
     LCMS: m/z 311 [M+H] +   
     HPLC retention time: 2.92 min (analysis condition Y) 
     Example 1162 
     Compound GT16-4 
     9-Methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To the DCM solution (1 ml) of 2-(1-benzofuran-2-yl-1-methylethyl)-5-methoxy benzoic acid (63 mg), trifluoroacetic anhydride (0.03 ml) was added at room temperature under nitrogen atmosphere. The mixture was stirred for 30 min. The reaction mixture was then added with water and extracted with DCM. The organic layer was dried over sodium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM) to obtain the title compound (50 mg, 84%). 
     LCMS: m/z 293 [M+H] +   
     HPLC retention time: 3.49 min (analysis condition Y) 
     Example 1163 
     Compound GT16-5 
     9-Hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound GT16-4. 
     LCMS: m/z 279 [M+H] +   
     HPLC retention time: 3.05 min (analysis condition Y) 
     Example 1164 
     Compound GT16-6 
     9-(2-Diethylamino-ethoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound GT16-5. 
     LCMS: m/z 378 [M+H] +   
     HPLC retention time: 2.41 min (analysis condition Y) 
     Example 1165 
     Compound GT16-7 
     9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound GT16-5 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester. 
     LCMS: m/z 393 [M+H] +   
     HPLC retention time: 3.22 min (analysis condition Y) 
     Example 1166 
     Compound GT16-8 
     9-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound GT16-7. 
     LCMS: m/z 353 [M+H] +   
     HPLC retention time: 2.83 min (analysis condition Y) 
     Example 1167 
     Compound GT16-9 
     3-(6,6-Dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-9-yl)-benzoic acid 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound GT9-2, the title compound was synthesized from Compound GT16-5. 
     LCMS: m/z 383 [M+H] +   
     HPLC retention time: 7.11 min (analysis condition H) 
     Example 1168 
     Compound GT16-10 
     9-(4-Hydroxymethyl-phenyl)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound GT9-2, the title compound was synthesized from Compound GT16-5. 
     LCMS: m/z 369 [M+H] +   
     HPLC retention time: 6.97 min (analysis condition H) 
     The compounds described in the following Table 39 were synthesized according to the method shown below. Specifically, Compound GT17-1 was prepared from 8-methoxy-1,1-dimethyl-3,4-dihydro-1H naphthalen-2-one and bromophenol by following the method that is used for the preparation of Compound Z10, Z11 and Z12. Compound GT17-1 was demethylated according to the method used for the preparation of Compound A6, and as a result 7-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared. The resulting hydroxy compound was subjected to the alkylation according to the method used for the preparation of A7-1, or Mitsunobu reaction used for the preparation of Compound A7-17 for introducing a corresponding side chain or a synthetic equivalent thereof. Thereafter, if necessary, functional group modification was carried out to prepare Compound GT17-2 and Compound GT17-3. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 39 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1169 
                 GT17-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-Methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11- one 
                 Y 
                 13.42 
                 293.0 
               
               
                   
               
               
                 1170 
                 GT17-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-(2-Diethylamino-ethoxy)-6,6- dimethyl-6H-benzo[b]naphtho[2,3- d]furan-11-one  
                 Y 
                 9.92 
                 378.0 
               
               
                   
               
               
                 1171 
                 GT17-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 7-((R)-2,3-Dihydroxy-propoxy)- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 Y 
                 11.68 
                 353.0 
               
               
                   
               
            
           
         
       
     
     The compounds described in the following Table 40 were synthesized according to the method shown below. 
     By using the method used for the preparation of Compound Z10, Z11 and Z12, Compound GT18-1 was prepared from Compound M1 and bromophenol. Further, according to the method used for the preparation of Compound A6, Compound GT18-1 was demethylated to prepare 8-hydroxy-11H-spiro[benzo[b]naphtho[2,3-d]furan-6,1′-cyclopentan]-11-one, which was then introduced with a side chain based on the alkylation that is used for the preparation of Compound A7-1. As a result, Compound GT18-2 was prepared. 
     The following spiro compounds were prepared from 7-methoxy-3,4-dihydro-TH-naphthalen-2-one and corresponding dibromide in the same manner as above. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 40 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1172 
                 GT18-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-methoxy-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,1′-cyclopentane]-11-one  
                 Y 
                 10.00 
                 319.0 
               
               
                   
               
               
                 1173 
                 GT18-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-diethylamino-ethoxy)-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,1′-cyclopentane]-11-one  
                 C 
                 2.19 
                 404.0 
               
               
                   
               
               
                 1174 
                 GT18-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-diethylamino-ethoxy)-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,1′-cyclohexane]-11-one  
                 C 
                 3.28 
                 418.2 
               
               
                   
               
               
                 1175 
                 GT18-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((2R,3R)-2,3,4- trihydroxybutoxy-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,1′-cyclohexane]-11-one  
                 A 
                 2.26 
                 423.2 
               
               
                   
               
               
                 1176 
                 GT18-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-methoxy-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,1′-cyclobutane]-11-one  
                 Y 
                 9.00 
                 305.0 
               
               
                   
               
               
                 1177 
                 GT18-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-(2-diethylamino-ethoxy)- 2′,3′,5′,6′-tetrahydro-11H- spiro[benzo[b]naphtho[2,3-d] furan-6,4′-pyran]-11-one  
                 B 
                 4.05 
                 420.3 
               
               
                   
               
            
           
         
       
     
     Example 1178 
     Compound GT19-1 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-trifluoromethyl-6H-benzo[B]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     According to the method described before, the preparation was carried out by using 7-methoxy-1,1-dimethyl-3,4-dihydro-1H naphthalen-2-one and 2-bromo-5-trifluorophenol. 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 3.25 min (analysis condition C) 
     Example 1179 
     Compound GT19-2 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-phenyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     By carrying out Suzuki coupling of Compound GT23-5 and a corresponding boronic acid reagent based on the method that is used for the preparation of Compound GT9-2, the title compound was prepared. 
     LCMS: m/z 454 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition F) 
     Example 1180 
     Compound GT20-1 
     8-Hydroxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (72.2 mg, 0.203 mmol), 2-phenylethanethiol (0.0297 ml, 0.221 mmol), Pd 2 dba 3  (9.3 mg, 0.0102 mmol), Xantphos (11.6 mg, 0.020 mmol) and ethyl diisopropylamine (0.068 ml, 0.40 mmol) were dissolved in dioxane (0.6 ml), and the mixture was stirred at 110° C. for 16 hrs under nitrogen atmosphere. Water and ethyl acetate were added to the mixture to give a suspension, which was then filtered. The organic layer was washed with water and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). The resulting residues were dissolved in THF (4 ml), and the supernatant liquid (2 ml) was taken and added with water (1 ml) and OXONE (99 mg). The resulting mixture was stirred at room temperature overnight. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (37.1 mg). 
     LCMS: m/z 446 [M+H] +   
     HPLC retention time: 2.51 min (analysis condition F) 
     Example 1181 
     Compound GT20-2 
     6,6-Dimethyl-3-(2-phenyl-ethanesulfonyl)-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one and 
     Compound GT20-3 
     8-Isopropoxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     8-Hydroxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one (30 mg, 0.0673 mmol), [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]methanol (22.3 mg, 0.0808 mmol), and PPh 3  (23 mg, 0.0875 mmol) were dissolved in THF (0.5 ml), added with DIAD (0.0169 ml, 0.0808 mmol), and the mixture was stirred at 50° C. overnight. After cooling, the reaction solution was filtered and concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). The resulting residues were dissolved in THF (0.4 ml) and water (0.13 ml), added with camphor sulfonic acid (28.1 mg, 0.121 mmol), and then subjected to microwave irradiation at 80° C. for 15 min under nitrogen atmosphere. Ethyl acetate was added to the resultant. The organic layer was washed with saturated aqueous solution of sodium hydrocarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (MeOH/DCM) to obtain Compound GT20-2 (10.5 mg) and Compound GT20-3 (2.4 mg). 
     Compound GT20-2 
     LCMS: m/z 550 [M+H] +   
     HPLC retention time: 2.20 min (analysis condition F) 
     Compound GT20-3 
     LCMS: m/z 488 [M+H] +   
     HPLC retention time: 3.13 min (analysis condition F) 
     Example 1182 
     Compound GT20-4 
     3-Methanesulfonyl-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     The DMA solution (0.6 ml) comprising Compound GT23-2 (59.6 mg, 0.167 mmol), sodium methanethiolate (77 mg, 1.10 mmol), Pd 2 dba 3  (23.7 mg, 0.0259 mmol) and Xantphos (29.7 mg, 0.0513 mmol) was subjected to microwave irradiation at 180° C. for 30 min under nitrogen atmosphere. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane and MeOH/DCM). The resulting solids were dissolved in THF (1 ml) and water (0.5 ml), and then added with OXONE (101.4 mg). The resulting mixture was stirred at room temperature for 2 hrs. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were suspended and washed with MTBE. The resulting solid was dissolved in THF (0.4 ml), and added with PPh 3  (37 mg, 0.141 mmol), [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (39.0 mg, 0.141 mmol) and DEAD (2.2 M toluene solution, 0.064 ml, 0.141 mmol), and the mixture was stirred at 40° C. for 4 hrs under nitrogen atmosphere. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (MeOH/DCM). Thus-obtained product was dissolved in THF (0.25 ml) and MeOH (0.05 ml), added with 0.5 M sulfuric acid (0.1 ml), and the mixture was stirred at 60° C. for 5 hrs. After cooling, the mixture was added with diethyl ether and sodium hydrocarbonate (13 mg, 0.15 mmol). The separated aqueous layer was filtered, concentrated under reduced pressure, and suspended and purified with MeOH to obtain the title compound as a white solid (10.4 mg, 14%). 
     LCMS: m/z 460 [M+H] +   
     HPLC retention time: 1.71 min (analysis condition F) 
     Example 1183 
     Compound GT20-5 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-methylsulfanyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (47.3 mg, 0.101 mmol), sodium methanethiolate (34.6 mg, 0.493 mmol), Pd 2 (dba) 3  (13.1 mg, 0.0413 mmol), and Xantphos (17.9 mg, 0.0309 mmol) were dissolved in DMA (0.5 ml) and subjected to microwave irradiation at 200° C. for 30 min under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (ethyl acetate/DCM). The resulting solid was dissolved in THF (0.23 ml) and MeOH (0.06 ml), and then added with 0.5 M sulfuric acid (0.12 ml). The resulting mixture was stirred at 60° C. for 2 hrs. The reaction solution was diluted with diethyl ether and neutralized with sodium hydrocarbonate (15.5 mg, 0.185 mmol). Thereafter, the solution was partitioned between brine and ethyl acetate. The organic layer was concentrated under reduced pressure. The resulting residues were added with diethyl ether. The precipitated solid was filtered to obtain the title compound as a white solid (15.8 mg, 39%). 
     LCMS: m/z 398 [M+H] +   
     HPLC retention time: 4.46 min (analysis condition H) 
     Example 1184 
     Compound GT20-5 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-thiazol-2-yl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (47 mg, 0.10 mmol), bis (pinacolate)diborone (33 mg, 0.13 mmol), Pd (dppf) 2 Cl 2 .DCM (8.2 mg, 0.010 mmol) and potassium acetate (294 mg, 0.3 mmol) were dissolved in dioxane (0.6 ml), and the mixture was stirred at 100° C. overnight under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/DCM) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5,6-dihydro-benzo[b]carbazol-11-one (30.2 mg). The product (11 mg) was dissolved in DMA (0.4 ml), added with 2-bromothiazole (0.0038 ml, 0.0428 mmol), Pd (PPh 3 ) 4  (5.3 mg, 0.00459 mmol), potassium phosphate (27.4 mg, 0.129 mmol) and water (0.1 ml), and the mixture was subjected to microwave irradiation at 140° C. for 7 min under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (MeOH/DCM). The resulting solid was dissolved in MeOH (1 ml), and then added with 1 N HCl (3 drops). The resulting mixture was stirred at 60° C. for 2 hrs. The reaction solution was concentrated under reduced pressure, and the residues obtained therefrom were suspended and washed with DCM/hexane (2/1) followed by drying to obtain the title compound as a yellow solid (8.7 mg). 
     LCMS: m/z 435 [M+H] +   
     HPLC retention time: 1.76 min (analysis condition A) 
     The compounds described in the following Table 41 were also synthesized in the same manner. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 41 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1185 
                 GT20-6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy-pro- poxy)-3-(1-methoxymethyl- 1H-midazol-2-yl)-6,6- dimethyl-5,6-dihydro- benzo[b]carbazol-11-one 
                 B 
                 2.63 
                 462.0 
               
               
                   
               
               
                 1186 
                 GT20-7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8-((R)-2,3-Dihydroxy- propoxy)-3-(1H- imidazol-2-yl)-6,6- dimethyl-5,6-dihydro- benzo[b]carbazol-11-one 
                 B 
                 2.45 
                 418.5 
               
               
                   
               
            
           
         
       
     
     Example 1187 
     Compound GT20-8 
     8-((R)-2,3-Dihydroxy-propoxy)-3-methoxymethyl-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one and 
     Compound GT20-9 
     8-((R)-2,3-Dihydroxy-propoxy)-3-hydroxymethyl-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one 
     
       
         
         
             
             
         
       
     
     3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (200.2 mg, 0.426 mmol), palladium acetate (II) (19 mg, 0.0848 mmol), hexacarbonyl molybdenum (115.5 mg, 0.438 mmol) and tris(o-tolyl)phosphine (52.5 mg, 0.172 mmol) were dissolved in THF (1.3 ml) and ethanol (0.075 ml), added with DBU (0.195 ml), and subjected to microwave irradiation at 160° C. for 15 min under nitrogen atmosphere. The resulting reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were dissolved in ethanol (10 ml) and THF (3 ml), added with 2 N KOH (2 ml), and stirred at room temperature for 2 hrs, at 50° C. overnight and at 70° C. for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were suspended and purified with MTBE/hexane (1/1) (155.4 mg). The THF solution (1.5 ml) of the product (109 mg) was added with TEA (0.052 ml, 0.373 mmol) and ethyl chloroformate (0.029 ml, 0.303 mmol) under ice cooling, and the mixture was stirred at 0° C. for 2 hrs. Subsequently, ethanol (1 ml) and sodium borohydride (75.7 mg, 2.0 mmol) were added to the mixture, which was then stirred at room temperature for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (MeOH/DCM) (35.2 mg). Thus-obtained solid (9.6 mg) was dissolved in MeOH (1 ml), added with 1 N HCl (3 drops), and the mixture was stirred at 60° C. for 90 min. After cooling and concentration under reduced pressure, the resultant was purified by TLC (MeOH/DCM) to obtain Compound GT20-8 (6.2 mg, white solid) and Compound GT20-9 (4.3 mg, white solid). 
     Compound GT20-8 
     LCMS: m/z 396 [M+H] +   
     HPLC retention time: 1.66 min (analysis condition A) 
     Compound GT20-9 
     LCMS: m/z 382 [M+H] +   
     HPLC retention time: 1.37 min (analysis condition A) 
     Example 1188 
     Compound GT21-1 
     8-[(E)-2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-vinyl]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To the DMF solution (4 ml) of trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester (300 mg), 2,2-dimethyl-4-vinyl-[1,3]dioxolane (469 mg) and PdCl 2 (PPh 3 ) 2  (103 mg), sodium hydrocarbonate (184 mg) was added, and the mixture was stirred at 100° C. overnight under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (130 mg, 46%). 
     LCMS: m/z 389 [M+H] +   
     HPLC retention time: 3.28 min (analysis condition Y) 
     Example 1189 
     Compound GT21-2 
     8-(3,4-Dihydroxy-butyl)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To the MeOH solution (5 ml) of 8-[(E)-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-vinyl]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (125 mg), 10% Pd—C(25 mg) was added and the mixture was stirred overnight at room temperature under hydrogen atmosphere. The catalyst was removed by filtration. The residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (35 mg, 31%). 
     LCMS: m/z 351 [M+H] +   
     HPLC retention time: 1.79 min (analysis condition Y) 
     Example 1190 
     Compound GT21-3 
     8-Amino-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester (100 mg), benzhydrylideneamine (0.05 ml), cesium carbonate (110 mg), palladium acetate (2 mg) and BINAP (7 mg), THF (2 ml) was added. The mixture was stirred and heated at 65° C. overnight under nitrogen atmosphere, and the reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (16 mg, 23%). 
     LCMS: m/z 278 [M+H] +   
     HPLC retention time: 2.52 min (analysis condition Y) 
     Example 1191 
     Compound GT21-4 
     8-[((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methyl)-amino]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     The mixture comprising 8-amino-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (50 mg), (R)-4-iodomethyl-2,2-dimethyl-[1,3]dioxolane (104 mg), potassium carbonate (150 mg) and DMF (2 ml) was stirred and heated at 160° C. for 2 days under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). To the compound (71 mg) obtained therefrom, THF (1 ml) and conc. hydrochloric acid (8 drops) were added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was added with saturated aqueous solution of sodium bicarbonate and then diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (34 mg, 51%). 
     LCMS: m/z 392 [M+H] +   
     HPLC retention time: 3.11 min (analysis condition Y) 
     Example 1192 
     Compound GT21-5 
     8-((S)-2,3-Dihydroxy-propylamino)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound A7-14-2, Compound GT21-4 was deprotected to obtain the title compound. 
     LCMS: m/z 352 [M+H] +   
     HPLC retention time: 2.26 min (analysis condition Y) 
     Example 1193 
     Compound GT22-1 
     8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-propyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To the mixture of trifluoro-methanesulfonic acid 8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-3-yl ester (15 mg), which had been obtained in the same manner as Compound A7-25, tris(1-methyl-3-oxo-1-butenyloxy) iron (III) (1 mg), NMP (0.3 ml) and THF (0.3 ml), n-PrMgBr (0.88 M, THF solution, 0.291 ml) and zinc chloride (0.5 M THF solution, 0.114 ml) were added at 0° C. under nitrogen atmosphere, and the mixture was stirred at 0° C. for 10 min. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (4.5 mg, 38%). 
     LCMS: m/z 420 [M+H] +   
     HPLC retention time: 5.77 min (analysis condition H) 
     Example 1194 
     Compound GT22-2 
     8-(2-Diethylamino-ethoxy)-3-ethyl-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound GT22-2, the title compound was synthesized. 
     LCMS: m/z 406 [M+H] +   
     HPLC retention time: 5.12 min (analysis condition B) 
     Example 1195 
     Compound GT23-1 
     3-Bromo-8-methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     8-Methoxy-6,6-dimethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-6H-benzo[b]naphtho[2,3-d]furan-11-one (10.3 mg), which had been synthesized from Compound Z12 under the same conditions as the method for synthesizing Compound GT20-5, was mixed with copper (II) bromide (16.5 mg), MeOH (0.5 ml) and water (0.25 ml), and the mixture was stirred and heated at 70° C. for 2 hrs. DCM was added to the reaction solution for extraction. The organic layer was concentrated and purified by silica gel column to obtain the title compound (9.4 mg). 
     LCMS: m/z 371 [M+H] +   
     HPLC retention time: 7.55 min (analysis condition B) 
     Example 1196 
     Compound GT23-2 
     3-Bromo-8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound GT15-5, 3-bromo-8-methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was deprotected to obtain the title compound. 
     LCMS: m/z 357 [M+H] +   
     HPLC retention time: 2.82 min (analysis condition A) 
     The compounds described in the following Table 42 were synthesized from Compound GT23-2 according to the method given in the Table. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 42 
               
             
            
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
                 Method 
               
               
                   
               
               
                 1197 
                 GT23-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Bromo-6,6-dimethyl- 8-((2R,3R)- 2,3,4-trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one 
                 D 
                 2.30 
                 461.0 
                 T22- 1-1 T22-2 
               
               
                   
               
               
                 1198 
                 GT23-4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Bromo-8- ((R)-2,3-dihydroxy- propoxy)- 6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one 
                 A 
                 5.42 
                 431.0 
                 A7- 14-1 A7- 14-2 
               
               
                   
               
               
                 1199 
                 GT23-5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Bromo-8-(2-diethyl- amino-ethoxy)-6,6-di- methyl-6H-benzo[b] naphtho[2,3-d]furan- 11-one 
                 H 
                 5.37 
                 456.0 
                 A7-17 
               
               
                   
               
            
           
         
       
     
     Example 1200 
     Compound GT24-1 
     8-((R)-2,3-Dihydroxy-propoxy)-3-iodo-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     To 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (15 mg, 0.032 mmol), CuI (6.2 mg, 0.032 mmol), NaI (9.6 mg, 0.064 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.01 ml) were added and the mixture was stirred for 48 hrs under nitrogen atmosphere. The reaction solution was diluted with ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-3-iodo-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (16 mg, 97%), which was then deprotected according to the method of A-14-2 to give the title compound. 
     LCMS: m/z 479 [M+H] +   
     HPLC retention time: 4.26 min (analysis condition A) 
     Example 1201 
     Compound GT24-2 
     3-Iodo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound GT24-1, 3-iodo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was synthesized from 3-bromo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one. Subsequently, according to the same method as Compound T22-2, deprotection was carried out to obtain the title compound. 
     Example 1202 
     Compound GT25-1 
     6,6-Dimethyl-8-(4-methyl-piperazine-1-sulfonyl)-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     By using the method for preparing Compound B1, trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester was prepared from 8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one. This trifluoromethanesulfonic acid ester (205 mg), (2R)-1-[(1R)-1-[bis (1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (13 mg), palladium acetate (6 mg), 2-trimethylsilanyl-ethanethiol (90 μL) and potassium carbonate (85 mg) were reacted in DME to obtain a product (120 mg). To the benzyl alcohol solution (90 μL) of the product (50 mg), DCM solution of N-chlorosuccinimide (90 mg) was added, and the mixture was stirred at room temperature. The reaction solution was partitioned between water and ethyl acetate, and the organic layer was concentrated under reduced pressure. To the DCM solution of thus-obtained white solid, N-methylpiperazine (10 μL) was added and the mixture was stirred. The residues obtained after removing the solvent by distillation were purified by TLC to obtain the title compound as a white solid (6 mg). 
     Example 1203 
     Compound GT26-1 
     (2-Bromo-5-methoxy-phenyl)-acetonitrile 
     
       
         
         
             
             
         
       
     
     To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na 2 SO 4  and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO 3  and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ 3.82 (s, 3H), 6.77 (d, 1H), 7.07 (s, 1H), 7.47 (d, 1H) 
     Example 1204 
     1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carbonitrile 
     Compound GT26-2 
     
       
         
         
             
             
         
       
     
     2-Bromo-5-methoxy-phenyl)-acetonitrile (12.2 g, 53.97 mmol) was dissolved in toluene (50 ml), and added with tetrabutylammonium bromide (3.55 g, 10.79 mmol), dibromoethane (7.05 ml, 80.95 mmol) and 50% aqueous solution of NaOH (50 ml) at room temperature. The mixture was stirred at room temperature for 4 hrs. The reaction mixture was added with water and extracted with ethyl acetate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane: ethyl acetate) to obtain the title compound (11.18 g, 82%). 
       1 H-NMR (400 MHz, CDCl 3 ) δ 1.33 (t, 1H), 1.76 (t, 1H), 3.79 (s, 3H), 6.75-6.79 (m, 1H), 6.89 (d, 1H), 7.47 (d, 1H) 
     Example 1205 
     1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carboxylic acid 
     Compound GT26-3 
     
       
         
         
             
             
         
       
     
     1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carbonitrile (3.0 g, 11.9 mmol) was dissolved in ethylene glycol (30 ml). After adding KOH (2.1 g, 33.3 mmol) thereto, the mixture was stirred and heated at 180° C. for 7 hrs. After cooling, the reaction mixture was added with 1 N HCl (90 ml). The reaction mixture was extracted with ether, washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the title compound was obtained (12.3 g, 72%). 
     LCMS: m/z 272 [M+H] +   
     HPLC retention time: 2.03 min (analysis condition Y) 
     Example 1206 
     Compound GT26-4 
     2-[1-(2-Bromo-5-methoxy-phenyl)-cyclopropyl]-benzofuran 
     
       
         
         
             
             
         
       
     
     To the DCM solution (6 ml) of 1-(2-bromo-5-methoxy-phenyl)-cyclopropane carboxylic acid (0.3 g, 1.1 mmol), DMF (2 drops) and oxalyl chloride (0.23 ml, 2.5 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hrs. The residues obtained from the reaction solution after concentration under reduced pressure were dissolved in toluene (6 ml), added with (2-hydroxybenzyl)triphenylphosphonium bromide (0.605 g, 1.32 mmol) and TEA (0.46 ml, 3.3 mmol), and the resulting mixture was stirred and heated at 100° C. overnight. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:DCM) to obtain the title compound (0.309 g, 81%). 
     LCMS: m/z 343 [M+H] +   
     HPLC retention time: 3.55 min (analysis condition Y) 
     Example 1207 
     Compound GT26-5 
     2-(1-Benzofuran-2-yl-cyclopropyl)-4-methoxy-benzoic acid 
     
       
         
         
             
             
         
       
     
     To the THF solution (3 ml) of 2-[1-(2-bromo-5-methoxy-phenyl)-cyclopropyl]-benzofuran (0.259 g, 0.75 mmol), n-BuLi was added at −78° C., and the mixture was stirred at −78° C. for 20 min. Thereafter, the mixture was flushed with carbon dioxide gas. The reaction mixture was added with saturated solution of NH 4 Cl and extracted with ethyl acetate. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM:MeOH) to obtain the title compound (0.163 g, 70%). 
     LCMS: m/z 309 [M+H] +   
     HPLC retention time: 2.67 min (analysis condition Y) 
     Example 1208 
     Compound GT26-6 
     8-Methoxy-11H-spiro[benzo[d]naphtho[2,3-b]furan-6,1′-cyclopropan]-11-one 
     
       
         
         
             
             
         
       
     
     To the DCM solution (10 ml) of 2-(1-benzofuran-2-yl-cyclopropyl)-4-methoxy-benzoic acid (1.0 g, 3.24 mmol), trifuloroacetic acid anhydride (0.45 ml, 3.24 mmol) was added at −78° C., and the mixture was stirred at −78° C. for 10 min, at −50° C. for 10 min, and at −30° C. for 20 min. Thereafter, the mixture was added with water and extracted with DCM. The residues obtained after concentration under reduced pressure were washed with DCM and hexane to obtain the title compound (0.163 g, 70%). 
     LCMS: m/z 291 [M+H] +   
     HPLC retention time: 2.90 min (analysis condition Y) 
     Example 1209 
     Compound GT26-7 
     8-(2-(Diethylamino)ethoxy)-11H-spiro[benzo[d]naphtho[2,3-b]furan-6,1′-cyclopropan]-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound A6 and Compound A7-17, the title compound was obtained from 8-methoxy-11H-spiro[benzo[d]naphtho[2,3-b]furan-6,1′-cyclopropan]-11-one. 
     LCMS: m/z 376 [M+H] +   
     HPLC retention time: 1.65 min (analysis condition Y) 
     Example 1210 
     Compound GT27-1 
     2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric acid 
     
       
         
         
             
             
         
       
     
     (2-Bromo-5-methoxy-phenyl)-acetic acid methyl ester (3.51 g, 13.5 mmol) was dissolved in DMF (4.5 ml), and added with NaH (2.1 g, 67.7 mmol). Subsequently, 15-crown-5 (1.38 ml, 6.8 mmol) and EtI (5.5 ml, 67.7 mmol) cooled to 0° C. were added to the mixture. The mixture was diluted with ethyl acetate and washed with water and saturated brine. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane-ethyl acetate). Then, the resultant was dissolved in ethanol (80 ml) and water (80 ml), added with KOH (91 g), and stirred at 140° C. The reaction solution was extracted with ethyl acetate, and washed with water and saturated brine. After concentration under reduced pressure, the target compound was obtained (10.62 g, 78%). 
     LCMS: m/z 301 [M+H] +   
     HPLC retention time: 3.07 min (analysis condition Y) 
     Example 1211 
     Compound GT27-2 
     2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric acid o-tolyl ester 
     
       
         
         
             
             
         
       
     
     Compound GT27-1 (0.5 g, 1.66 mmol) was dissolved in DCM (10 ml), added with DMF (2 drops) and oxalyl chloride (0.28 ml, 3.32 mmol), and the mixture was stirred for 2 hrs. The reaction mixture obtained after concentration under reduced pressure was dissolved in toluene (5 ml), added with DMAP (406 mg, 3.32 mmol), and the mixture was heated under reflux. The reaction mixture was extracted with ethyl acetate, washed with 1 N HCl, and saturated brine. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane-ethyl acetate) to obtain the target compound (0.36 g, 86%). 
     LCMS: m/z 393 [M+H] +   
     HPLC retention time: 3.03 min (analysis condition Y) 
     Example 1212 
     Compound GT27-3 
     2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric acid 2-[(triphenyl-phosphanyl)-methyl]-phenyl ester bromate salt 
     
       
         
         
             
             
         
       
     
     Compound GT27-2 (0.118 g, 0.302 mmol) was dissolved in carbon tetrachloride (3 ml), added with N-bromosuccinimide (54 mg, 0.302 mmol), and the mixture was heated under reflux. The reaction mixture was concentrated under reduced pressure and the resulting residues were purified by silica gel column (ethyl acetate-hexane). The product was dissolved in toluene (3 ml), added with PPh 3  (77 mg, 0.302 mmol), and the mixture was heated under reflux. The reaction mixture was concentrated under reduced pressure to obtain the target compound (130 mg, 57%). 
     Example 1213 
     Compound GT27-4 
     2-[1-(2-Bromo-5-methoxy-phenyl)-1-ethyl-propyl]-benzofuran 
     
       
         
         
             
             
         
       
     
     To the toluene solution (3 ml) of Compound GT27-3 (0.14 g, 0.137 mmol), toluene solution (0.16 ml, 0.164 mmol) of 1 M LiHMDS was added. The mixture was heated and stirred for 4 hrs. The reaction mixture was concentrated under reduced pressure and the resulting residues were purified by silica gel column (ethyl acetate: hexane) to obtain the title compound (28 mg, 35%). 
     LCMS: m/z 373 [M+H] +   
     HPLC retention time: 2.73 min (analysis condition Y) 
     Example 1214 
     Compound GT27-5 
     8-(2-Diethylamino-ethoxy)-6,6-diethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound A7-17, the title compound was obtained from Compound GT27-4. 
     LCMS: m/z 407 [M+H] +   
     HPLC retention time: 1.92 min (analysis condition Y) 
     Example 1215 
     Compound GT27-6 
     8-((R)-2,3-Dihydroxy-propoxy)-6,6-diethyl-6H benzo[b]naphtho[2,3-d]furan-11-one 
     
       
         
         
             
             
         
       
     
     In the same manner as Compound A7-14-1 and Compound A7-14-2, the title compound was obtained from Compound GT27-4. 
     LCMS: m/z 381 [M+H] +   
     HPLC retention time: 2.38 min (analysis condition Y) 
     The compounds described in the following Table 43 were synthesized according to the method shown below. According to the method used for the preparation of Compound Z10, Z11 and Z12, 3-chloro-8-methoxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared from Compound A2 and 2-bromo-5-chlorophenol. Subsequently, demethylation was carried out according to the method that is used for the preparation of Compound A6, and thus 3-chloro-8-hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was obtained. Thereafter, according to Mitsunobu reaction that is used for the preparation of Compound A7-1 or the alkylation method that is used for the preparation of A7-17, a corresponding side chain was introduced and, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 43 
               
               
                   
               
               
                 Exam- 
                 Comp. 
                   
                   
                 HPLC 
                 Retention 
                   
               
               
                 ple No. 
                 No. 
                 Structure 
                 Compound Name 
                 Condition 
                 Time 
                 m/z 
               
               
                   
               
             
            
               
                 1216 
                 GT28-1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-8-(2-diethylamino- ethoxy)-6,6-dimethyl-6H-benzo [b]naphtho[2,3-d]furan-11-one 
                 F 
                 2.52 
                 412.0 
               
               
                   
               
               
                 1217 
                 GT28-2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-6,6-dimethyl-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6H- benzo[b]naphtho[2,3-d]furan-11-one 
                 H 
                 5.39 
                 417.0 
               
               
                   
               
               
                 1218 
                 GT28-3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3-Chloro-8-((R)-2,3-dihydroxy- propoxy)-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one 
                 H 
                 5.77 
                 387.0 
               
               
                   
               
            
           
         
       
     
     Pharmacological Testing Method 
     1. Activity of Inhibiting ALK Enzyme 
     ALK-inhibiting activity was measured by following an activity of inhibiting phosphorylation by biotinylated peptide (EGPWLEEEEEAYGWMDF). For the detection of phosphorylation of the biotinylated peptide, time-resolved fluorescence measurement was performed using an anti-phosphorylated tyrosine antibody labeled with europium cryptate and streptavidin conjugated to XL665, i.e., an allophycocyanin derivative. From the inhibition ratio compared to the control group that does not comprise a test compound, 50% inhibitory concentration (i.e., IC 50  value) was calculated. 
     2. Measurement of an Activity of Inhibiting Karpas-299 Cell Growth 
     The test compounds were serially diluted with dimethyl sulfoxide, further diluted with phosphate buffered saline which is free of any Ca 2+ , Mg 2+  (×50 dilution), and 10 μL of the resulting solution was aliquoted in a 96-well plate. Human lymphoma cell line KARPAS-299 was prepared in RPMI-1640 medium to which 10% bovine fetal serum was added to give a cell suspension with the cell density of 10,000 cells/190 μL. The resulting cell suspension was aliquoted to the plate (190 μL per well) to which the test compound had been already added, and the plate was kept in a 5% carbon dioxide gas incubator at 37° C. Ninety-six hours later, 10 μL of WST-8 (manufactured by Dojindo Laboratories) was added to each well, and subsequently the absorbance was measured at 450 nm. From the ratio of inhibition on cell growth which had been obtained from the addition of a test compound compared to the control group with no addition, 50% growth inhibitory concentration (i.e., IC 50  value) of the test compound was calculated. The results are summarized in Tables 44-49. 
     
       
         
           
               
               
               
             
               
                 TABLE 44 
               
               
                   
               
               
                   
                   
                 Inhibitory activity 
               
               
                   
                 ALK-inhibiting 
                 on Karpas-299 
               
               
                   
                 activity IC 50   
                 cell growth IC 50   
               
               
                 Examples 
                 (μM) 
                 (μM) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                  123 (Compound B2-27) 
                 0.00228 
                 0.0138 
               
               
                  177 (Compound B4-7) 
                 0.00084 
                 0.0105 
               
               
                  178 (Compound B4-8) 
                 0.00153 
                 0.0214 
               
               
                  304 (Compound F5-11) 
                 0.00081 
                 0.0061 
               
               
                  338 (Compound F5-43) 
                 0.00032 
                 0.0086 
               
               
                  341 (Compound F5-46) 
                 0.01056 
                 0.0289 
               
               
                  364 (Compound F6-18) 
                 0.00177 
                 0.0231 
               
               
                  366 (Compound F6-20) 
                 0.0053 
                 0.0093 
               
               
                  372 (Compound G6) 
                 0.03074 
                 0.1682 
               
               
                  380 (Compound H6-2) 
                 0.00053 
                 0.0062 
               
               
                  429 (Compound J7-10-2) 
                 0.00083 
                 0.0303 
               
               
                  543 (Compound O8-5) 
                 0.00032 
                 0.03 
               
               
                  550 (Compound O9-7) 
                 0.00090 
                 0.0044 
               
               
                  735 (Compound Z7) 
                 0.09385 
                 1.1924 
               
               
                  516 (Compound N6-2) 
                 0.003906748 
                 0.0248 
               
               
                  725 (Compound X5) 
                 0.687683357 
                 2.8765 
               
               
                  882 (Compound AZ7-10) 
                 0.000493765 
                 0.005769 
               
               
                  916 (Compound DZ7-1) 
                 0.001836659 
                 0.357381 
               
               
                  937 (Compound EZ9-3) 
                 0.006473484 
                 0.056914 
               
               
                  939 (Compound EZ9-5) 
                 0.399865279 
                 13.421227 
               
               
                 1175 (Compound GT18-4) 
                 0.093 
                 2.012 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 45 
               
               
                   
                   
               
               
                   
                   
                   
                 ALK-inhibiting 
               
               
                   
                 Example 
                   
                 activity IC 50   
               
               
                   
                 No. 
                 Compound 
                 (μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  13 
                 A7-1 
                 0.052707597 
               
               
                   
                  14 
                 A7-2 
                 0.006159417 
               
               
                   
                  38 
                 A7-20 
                 0.026183852 
               
               
                   
                  39 
                 A7-21 
                 0.017713716 
               
               
                   
                  40 
                 A7-22 
                 0.030434111 
               
               
                   
                  41 
                 A7-23 
                 0.029469872 
               
               
                   
                  45 
                 A8-2 
                 0.008009528 
               
               
                   
                  47 
                 A8-4 
                 0.010253392 
               
               
                   
                  51 
                 A8-6-3 
                 0.097920152 
               
               
                   
                  52 
                 A8-7 
                 0.045959643 
               
               
                   
                  55 
                 A8-10 
                 0.00673264 
               
               
                   
                  57 
                 A8-12 
                 0.003594618 
               
               
                   
                  63 
                 A8-18 
                 0.016005139 
               
               
                   
                  65 
                 A8-20 
                 0.0029 
               
               
                   
                  67 
                 A9-1 
                 0.004943 
               
               
                   
                  70 
                 A9-3-2 
                 0.007649647 
               
               
                   
                  73 
                 A9-6-2 
                 0.001398207 
               
               
                   
                  74 
                 A9-7 
                 0.0034607 
               
               
                   
                  76 
                 A9-9 
                 0.017148495 
               
               
                   
                  78 
                 A9-11 
                 0.051123952 
               
               
                   
                  79 
                 A9-12 
                 0.017501168 
               
               
                   
                  83 
                 A9-15-2 
                 0.0035 
               
               
                   
                  84 
                 A9-16 
                 0.08468 
               
               
                   
                  90 
                 B2-1 
                 0.033572 
               
               
                   
                 100 
                 B2-9 
                 0.016225317 
               
               
                   
                 101 
                 B2-10 
                 0.039433518 
               
               
                   
                 102 
                 B2-11 
                 0.072607257 
               
               
                   
                 104 
                 B2-13 
                 0.001681324 
               
               
                   
                 109 
                 B2-16-3 
                 0.000980809 
               
               
                   
                 117 
                 B2-23 
                 0.005436966 
               
               
                   
                 118 
                 B2-24 
                 0.014834642 
               
               
                   
                 122 
                 B2-26-2 
                 0.007278245 
               
               
                   
                 124 
                 B2-28 
                 0.059632226 
               
               
                   
                 128 
                 B3-2-2 
                 0.003183521 
               
               
                   
                 130 
                 B3-4 
                 0.063798146 
               
               
                   
                 135 
                 B3-9 
                 0.01492317 
               
               
                   
                 137 
                 B3-11 
                 0.071084446 
               
               
                   
                 141 
                 B3-14 
                 0.011893599 
               
               
                   
                 142 
                 B3-15 
                 0.030133825 
               
               
                   
                 143 
                 B3-16 
                 0.027324427 
               
               
                   
                 146 
                 B3-19 
                 0.010369469 
               
               
                   
                 147 
                 B3-20 
                 0.026851192 
               
               
                   
                 149 
                 B3-22 
                 0.272356381 
               
               
                   
                 150 
                 B3-23 
                 0.023088404 
               
               
                   
                 151 
                 B3-24 
                 0.003610645 
               
               
                   
                 157 
                 B3-27-2 
                 0.002114607 
               
               
                   
                 158 
                 B3-28 
                 0.042375341 
               
               
                   
                 159 
                 B3-29 
                 0.006002322 
               
               
                   
                 165 
                 B3-34 
                 0.006783031 
               
               
                   
                 166 
                 B3-35 
                 0.003473067 
               
               
                   
                 168 
                 B3-37 
                 0.011859342 
               
               
                   
                 179 
                 B4-9 
                 0.002000975 
               
               
                   
                 187 
                 CC4-2 
                 0.096115639 
               
               
                   
                 189 
                 C1-1 
                 0.051102036 
               
               
                   
                 206 
                 C4-9 
                 0.005101172 
               
               
                   
                 210 
                 C4-13 
                 0.008752733 
               
               
                   
                 212 
                 C4-15 
                 0.009616778 
               
               
                   
                 226 
                 D1 
                 0.000991134 
               
               
                   
                 227 
                 D2 
                 0.003611773 
               
               
                   
                 228 
                 D3-1 
                 0.006279559 
               
               
                   
                 245 
                 E4-5 
                 0.009450575 
               
               
                   
                 256 
                 E5-2 
                 0.00133756 
               
               
                   
                 264 
                 E6-2 
                 0.006668071 
               
               
                   
                 265 
                 E6-3 
                 0.008113087 
               
               
                   
                 268 
                 F1-3 
                 0.005054399 
               
               
                   
                 277 
                 F3-6-2 
                 0.000167996 
               
               
                   
                 283 
                 F4-1-1 
                 0.001625048 
               
               
                   
                 286 
                 F4-3 
                 0.000951804 
               
               
                   
                 290 
                 F4-7 
                 0.001133931 
               
               
                   
                 293 
                 F4-10 
                 0.002098847 
               
               
                   
                 298 
                 F5-5 
                 0.002385717 
               
               
                   
                 300 
                 F5-7 
                 0.002575475 
               
               
                   
                 306 
                 F5-13 
                 0.002051837 
               
               
                   
                 314 
                 F5-20 
                 0.000996109 
               
               
                   
                 319 
                 F5-25 
                 0.000881378 
               
               
                   
                 322 
                 F5-28 
                 0.01227125 
               
               
                   
                 331 
                 F5-36-2 
                 0.001778367 
               
               
                   
                 334 
                 F5-39 
                 0.014824288 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 46 
               
               
                   
                   
               
               
                   
                   
                   
                 ALK-inhibiting 
               
               
                   
                 Example 
                   
                 activity IC 50    
               
               
                   
                 No. 
                 Compound 
                 (μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 340 
                 F5-45 
                 0.000579745 
               
               
                   
                 346 
                 F5-51 
                 0.002610782 
               
               
                   
                 350 
                 F6-4 
                 0.00715425 
               
               
                   
                 353 
                 F6-7 
                 0.020276801 
               
               
                   
                 355 
                 F6-9 
                 0.001092627 
               
               
                   
                 358 
                 F6-12 
                 0.015047658 
               
               
                   
                 359 
                 F6-13 
                 0.000399685 
               
               
                   
                 389 
                 H9-3 
                 0.002622129 
               
               
                   
                 403 
                 I6-4 
                 0.000391036 
               
               
                   
                 407 
                 I7-1 
                 0.001863642 
               
               
                   
                 421 
                 J7-3 
                 0.015290853 
               
               
                   
                 422 
                 J7-4 
                 0.004631153 
               
               
                   
                 423 
                 J7-5 
                 0.012009506 
               
               
                   
                 424 
                 J7-6 
                 0.001570404 
               
               
                   
                 426 
                 J7-8 
                 0.001170682 
               
               
                   
                 431 
                 J7-11-2 
                 0.01172814 
               
               
                   
                 435 
                 J7-15 
                 0.02319 
               
               
                   
                 437 
                 J7-17 
                 0.007091939 
               
               
                   
                 438 
                 J8-1 
                 0.012517614 
               
               
                   
                 443 
                 J8-6 
                 0.00396 
               
               
                   
                 455 
                 JJ5 
                 0.862941682 
               
               
                   
                 458 
                 JJ7-2 
                 0.028993627 
               
               
                   
                 461 
                 JJ9-1 
                 0.004337558 
               
               
                   
                 465 
                 JJ10-1 
                 0.492725332 
               
               
                   
                 472 
                 K6 
                 0.029284532 
               
               
                   
                 486 
                 K10-5 
                 0.000589765 
               
               
                   
                 501 
                 L10-2 
                 0.00160 
               
               
                   
                 508 
                 M6-2 
                 0.006136762 
               
               
                   
                 517 
                 N6-3 
                 0.03272871 
               
               
                   
                 519 
                 N6-5 
                 0.026853329 
               
               
                   
                 531 
                 O5-4 
                 0.00431 
               
               
                   
                 546 
                 O9-3 
                 0.00086 
               
               
                   
                 571 
                 Q8 
                 0.005719259 
               
               
                   
                 579 
                 R8-2 
                 0.000769618 
               
               
                   
                 591 
                 S4 
                 1.664818863 
               
               
                   
                 599 
                 S8-2 
                 0.04064 
               
               
                   
                 601 
                 S9-2 
                 0.000456356 
               
               
                   
                 607 
                 T2-1 
                 0.432812267 
               
               
                   
                 618 
                 T6-1 
                 0.614075453 
               
               
                   
                 621 
                 T6-4 
                 0.341433432 
               
               
                   
                 628 
                 T11 
                 0.271479209 
               
               
                   
                 630 
                 T12-2 
                 0.15422 
               
               
                   
                 633 
                 T13-3 
                 0.16211 
               
               
                   
                 637 
                 T13-7 
                 0.16821 
               
               
                   
                 639 
                 T13-9 
                 0.16189 
               
               
                   
                 645 
                 T14-5 
                 0.41327 
               
               
                   
                 650 
                 T14-10 
                 0.18923 
               
               
                   
                 654 
                 T16-1 
                 0.01951 
               
               
                   
                 657 
                 T16-4 
                 0.07941 
               
               
                   
                 668 
                 T21 
                 0.8521 
               
               
                   
                 671 
                 T22-1-1 
                 0.151061541 
               
               
                   
                 678 
                 T22-7 
                 2.8135 
               
               
                   
                 679 
                 T22-8 
                 0.583 
               
               
                   
                 686 
                 T26-2 
                 0.08320 
               
               
                   
                 702 
                 U8-6-2 
                 0.00260 
               
               
                   
                 704 
                 U8-7-2 
                 0.00604 
               
               
                   
                 706 
                 U8-8-2 
                 0.35976 
               
               
                   
                 707 
                 U8-8-3 
                 0.84884 
               
               
                   
                 709 
                 U10-1 
                 0.55215 
               
               
                   
                 711 
                 U11 
                 0.00193 
               
               
                   
                 720 
                 W4-2 
                 0.13445 
               
               
                   
                 730 
                 Y5-2 
                 0.554738402 
               
               
                   
                 751 
                 K10-10 
                 0.0085 
               
               
                   
                 753 
                 K10-12 
                 0.0022 
               
               
                   
                 755 
                 K10-14 
                 0.0118 
               
               
                   
                 758 
                 K10-17 
                 0.1422 
               
               
                   
                 760 
                 K10-19 
                 0.0015 
               
               
                   
                 762 
                 L10-3 
                 0.0099 
               
               
                   
                 770 
                 L10-11 
                 0.0231 
               
               
                   
                 776 
                 B3-42 
                 0.0042 
               
               
                   
                 786 
                 E9-4 
                 0.0004 
               
               
                   
                 790 
                 E9-8 
                 0.0075 
               
               
                   
                 796 
                 F4-11 
                 0.0003 
               
               
                   
                 822 
                 PR11-6 
                 0.0003 
               
               
                   
                 823 
                 PRH-7 
                 0.0003 
               
               
                   
                 824 
                 PR9-9 
                 0.0142 
               
               
                   
                 829 
                 PR9-13 
                 0.0007 
               
               
                   
                 832 
                 PR11-11 
                 0.0006 
               
               
                   
                 846 
                 PR9-25 
                 0.021743738 
               
               
                   
                 847 
                 PR11-14 
                 0.001890642 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 47 
               
               
                   
                   
               
               
                   
                   
                   
                 ALK-inhibiting 
               
               
                   
                 Example 
                   
                 activity IC 50   
               
               
                   
                 No. 
                 Compound 
                 (μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  849 
                 PR11-16 
                 0.000813047 
               
               
                   
                  864 
                 LB5-1 
                 0.424843491 
               
               
                   
                  866 
                 LB5-3 
                 2.398295 
               
               
                   
                  875 
                 AZ7-3 
                 0.113911239 
               
               
                   
                  892 
                 AZ7-20 
                 0.009369855 
               
               
                   
                  893 
                 AZ7-21 
                 0.142933634 
               
               
                   
                  920 
                 DZ7-5 
                 0.326374265 
               
               
                   
                  938 
                 EZ9-4 
                 0.300760062 
               
               
                   
                  949 
                 GT2-6 
                 1.3255 
               
               
                   
                  956 
                 GT2-13 
                 0.1617 
               
               
                   
                  960 
                 GT3-2 
                 5.9473 
               
               
                   
                  962 
                 GT3-4 
                 1.0829 
               
               
                   
                  963 
                 GT3-5 
                 4.224 
               
               
                   
                  967 
                 GT3-9 
                 0.8981 
               
               
                   
                  970 
                 GT3-12 
                 1.6214 
               
               
                   
                  972 
                 GT4-1 
                 0.29 
               
               
                   
                  973 
                 GT4-2 
                 0.104 
               
               
                   
                  981 
                 GT5-8 
                 2.9743 
               
               
                   
                  982 
                 GT5-9 
                 21.3078 
               
               
                   
                  983 
                 GT5-10 
                 3.2 
               
               
                   
                  994 
                 GT5-21 
                 1.2466 
               
               
                   
                  995 
                 GT6-1 
                 12.9519 
               
               
                   
                  996 
                 GT6-2 
                 12.9704 
               
               
                   
                  997 
                 GT6-3 
                 0.575 
               
               
                   
                  998 
                 GT6-4 
                 4.3855 
               
               
                   
                  999 
                 GT6-5 
                 3.9 
               
               
                   
                 1000 
                 GT6-6 
                 5.4 
               
               
                   
                 1001 
                 GT6-7 
                 3.7 
               
               
                   
                 1004 
                 GT6-10 
                 0.9 
               
               
                   
                 1005 
                 GT6-11 
                 1.4385 
               
               
                   
                 1007 
                 GT6-13 
                 0.7526 
               
               
                   
                 1008 
                 GT6-14 
                 4.8429 
               
               
                   
                 1013 
                 GT8-3 
                 0.93 
               
               
                   
                 1017 
                 GT9-3 
                 0.3785 
               
               
                   
                 1019 
                 GT9-5 
                 0.77 
               
               
                   
                 1030 
                 GT11-8 
                 5.9346 
               
               
                   
                 1031 
                 GT11-9 
                 7.7947 
               
               
                   
                 1034 
                 GT11-12 
                 2.076 
               
               
                   
                 1035 
                 GT11-13 
                 1.6274 
               
               
                   
                 1039 
                 GT11-17 
                 0.7938 
               
               
                   
                 1042 
                 GT11-20 
                 0.5083 
               
               
                   
                 1043 
                 GT11-21 
                 2.2822 
               
               
                   
                 1047 
                 GT11-25 
                 1.9038 
               
               
                   
                 1048 
                 GT11-26 
                 5.3708 
               
               
                   
                 1050 
                 GT11-28 
                 3.2813 
               
               
                   
                 1051 
                 GT11-29 
                 1.811 
               
               
                   
                 1052 
                 GT11-30 
                 4.0931 
               
               
                   
                 1054 
                 GT11-32 
                 7.0451 
               
               
                   
                 1059 
                 GT11-37 
                 2.7739 
               
               
                   
                 1060 
                 GT11-38 
                 1.1587 
               
               
                   
                 1061 
                 GT11-39 
                 1.0914 
               
               
                   
                 1065 
                 GT11-43 
                 3.7028 
               
               
                   
                 1066 
                 GT11-44 
                 3.1203 
               
               
                   
                 1072 
                 GT11-50 
                 3.3428 
               
               
                   
                 1073 
                 GT11-51 
                 2.547 
               
               
                   
                 1074 
                 GT11-52 
                 1.2588 
               
               
                   
                 1081 
                 GT11-59 
                 1.0586 
               
               
                   
                 1083 
                 GT11-61 
                 0.7928 
               
               
                   
                 1085 
                 GT11-63 
                 0.9013 
               
               
                   
                 1086 
                 GT11-64 
                 0.3127 
               
               
                   
                 1087 
                 GT11-65 
                 0.206 
               
               
                   
                 1090 
                 GT12-3 
                 0.8541 
               
               
                   
                 1096 
                 GT12-9 
                 5.7571 
               
               
                   
                 1102 
                 GT13-3 
                 0.4209 
               
               
                   
                 1105 
                 GT13-6 
                 0.3894 
               
               
                   
                 1113 
                 GT13-14 
                 0.1571 
               
               
                   
                 1114 
                 GT13-15 
                 0.7 
               
               
                   
                 1117 
                 GT13-18 
                 2.2 
               
               
                   
                 1118 
                 GT13-19 
                 0.5 
               
               
                   
                 1119 
                 GT13-20 
                 0.42 
               
               
                   
                 1125 
                 GT13-26 
                 0.028 
               
               
                   
                 1126 
                 GT13-27 
                 3.0645 
               
               
                   
                 1127 
                 GT13-28 
                 5.6311 
               
               
                   
                 1128 
                 GT13-29 
                 17.4641 
               
               
                   
                 1129 
                 GT13-30 
                 0.51 
               
               
                   
                 1130 
                 GT13-31 
                 0.54 
               
               
                   
                 1164 
                 GT16-5 
                 0.4149 
               
               
                   
                 1177 
                 GT18-6 
                 0.7527 
               
               
                   
                 1185 
                 GT20-6 
                 1.8 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 48 
               
               
                   
                   
               
               
                   
                   
                   
                 Inhibitory activity 
               
               
                   
                   
                   
                 on Karpas-299 
               
               
                   
                   
                   
                 cell growth 
               
               
                   
                 Example 
                   
                 IC 50   
               
               
                   
                 No. 
                 Compound 
                 (μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  15 
                 A7-3 
                 0.1138 
               
               
                   
                  17 
                 A7-5 
                 0.6268 
               
               
                   
                  19 
                 A7-7 
                 0.3293 
               
               
                   
                  21 
                 A7-9 
                 0.2037 
               
               
                   
                  22 
                 A7-10 
                 0.3031 
               
               
                   
                  25 
                 A7-12 
                 0.1119 
               
               
                   
                  46 
                 A8-3 
                 0.0866 
               
               
                   
                  56 
                 A8-11 
                 0.0677 
               
               
                   
                  58 
                 A8-13 
                 0.0226 
               
               
                   
                  60 
                 A8-15 
                 0.2322 
               
               
                   
                  61 
                 A8-16 
                 0.0345 
               
               
                   
                  62 
                 A8-17 
                 0.1269 
               
               
                   
                  64 
                 A8-19 
                 0.0726 
               
               
                   
                  66 
                 A8-21 
                 0.1050 
               
               
                   
                  68 
                 A9-2 
                 0.1372 
               
               
                   
                  72 
                 A9-5 
                 0.0523 
               
               
                   
                  93 
                 B2-4 
                 0.0365 
               
               
                   
                 138 
                 B3-12 
                 1.4358 
               
               
                   
                 154 
                 B3-25-3 
                 0.7298 
               
               
                   
                 155 
                 B3-26 
                 1.3613 
               
               
                   
                 160 
                 B3-30 
                 0.2282 
               
               
                   
                 163 
                 B3-32 
                 0.0652 
               
               
                   
                 167 
                 B3-36 
                 0.0390 
               
               
                   
                 174 
                 B4-4 
                 0.0812 
               
               
                   
                 229 
                 D3-2 
                 0.9700 
               
               
                   
                 230 
                 D3-3 
                 0.1320 
               
               
                   
                 244 
                 E4-4 
                 0.1090 
               
               
                   
                 257 
                 E5-3 
                 0.1895 
               
               
                   
                 260 
                 E5-6 
                 0.0527 
               
               
                   
                 273 
                 F3-3 
                 0.0162 
               
               
                   
                 287 
                 F4-4 
                 0.0071 
               
               
                   
                 289 
                 F4-6 
                 0.0291 
               
               
                   
                 291 
                 F4-8 
                 0.0221 
               
               
                   
                 292 
                 F4-9 
                 0.0650 
               
               
                   
                 294 
                 F5-1 
                 0.0091 
               
               
                   
                 297 
                 F5-4 
                 0.0018 
               
               
                   
                 301 
                 F5-8 
                 0.0297 
               
               
                   
                 302 
                 F5-9 
                 0.0043 
               
               
                   
                 303 
                 F5-10 
                 0.0135 
               
               
                   
                 309 
                 F5-15-2 
                 0.0098 
               
               
                   
                 310 
                 F5-16 
                 0.0042 
               
               
                   
                 315 
                 F5-21 
                 0.0663 
               
               
                   
                 316 
                 F5-22 
                 0.0066 
               
               
                   
                 323 
                 F5-29 
                 0.0076 
               
               
                   
                 325 
                 F5-31 
                 0.0727 
               
               
                   
                 326 
                 F5-32 
                 0.0240 
               
               
                   
                 335 
                 F5-40 
                 0.0256 
               
               
                   
                 336 
                 F5-41 
                 0.1491 
               
               
                   
                 339 
                 F5-44 
                 0.0060 
               
               
                   
                 348 
                 F6-2 
                 0.0295 
               
               
                   
                 351 
                 F6-5 
                 0.0274 
               
               
                   
                 352 
                 F6-6 
                 0.0364 
               
               
                   
                 357 
                 F6-11 
                 0.0776 
               
               
                   
                 359 
                 F6-13 
                 0.0079 
               
               
                   
                 420 
                 J7-2-3 
                 0.0295 
               
               
                   
                 434 
                 J7-14 
                 0.5567 
               
               
                   
                 446 
                 J9-3 
                 0.0532 
               
               
                   
                 467 
                 JJ10-3 
                 6.0632 
               
               
                   
                 488 
                 K10-7 
                 0.0518 
               
               
                   
                 518 
                 N6-4 
                 0.1224 
               
               
                   
                 562 
                 P5 
                 27.7670 
               
               
                   
                 605 
                 T1-1 
                 1.8669 
               
               
                   
                 636 
                 T13-6 
                 1.2901 
               
               
                   
                 640 
                 T13-10 
                 1.3775 
               
               
                   
                 642 
                 T14-2 
                 0.6324 
               
               
                   
                 646 
                 T14-6 
                 1.9418 
               
               
                   
                 649 
                 T14-9 
                 1.08 
               
               
                   
                 656 
                 T16-3 
                 2.25 
               
               
                   
                 672 
                 T22-1-2 
                 1.7820 
               
               
                   
                 680 
                 T23-1 
                 4.2526 
               
               
                   
                 681 
                 T23-2 
                 7.0799 
               
               
                   
                 688 
                 T27-2 
                 0.9970 
               
               
                   
                 689 
                 U5 
                 0.1217 
               
               
                   
                 695 
                 U8-3-2 
                 0.6773 
               
               
                   
                 698 
                 U8-4-3 
                 1.10 
               
               
                   
                 700 
                 U8-5-2 
                 0.3573 
               
               
                   
                 708 
                 U9 
                 0.4070 
               
               
                   
                 710 
                 U10-2 
                 0.94 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 49 
               
               
                   
                   
               
               
                   
                   
                   
                 Inhibitory activity 
               
               
                   
                   
                   
                 on Karpas-299  
               
               
                   
                   
                   
                 cell growth 
               
               
                   
                 Example 
                   
                 IC 50   
               
               
                   
                 No. 
                 Compound 
                 (μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                  764 
                 L10-5 
                 0.019 
               
               
                   
                  766 
                 L10-7 
                 0.037 
               
               
                   
                  767 
                 L10-8 
                 0.024 
               
               
                   
                  769 
                 L10-10 
                 0.159 
               
               
                   
                  773 
                 B3-40 
                 0.022 
               
               
                   
                  787 
                 E9-5 
                 0.041 
               
               
                   
                  792 
                 E9-9 
                 0.004 
               
               
                   
                  793 
                 PR11-20 
                 0.020313 
               
               
                   
                  794 
                 PR11-21 
                 0.06439 
               
               
                   
                  827 
                 PR9-11 
                 0.036 
               
               
                   
                  839 
                 PR9-20 
                 0.018772 
               
               
                   
                  844 
                 PR9-23 
                 0.020492 
               
               
                   
                  845 
                 PR9-24 
                 0.067888 
               
               
                   
                  850 
                 PR11-17 
                 0.005766 
               
               
                   
                  852 
                 PR11-19 
                 0.034632 
               
               
                   
                  865 
                 LB5-2 
                 1.287666 
               
               
                   
                  878 
                 AZ7-6 
                 1.126471 
               
               
                   
                  896 
                 AZ7-24 
                 0.054 
               
               
                   
                  935 
                 EZ9-1 
                 16.635 
               
               
                   
                  941 
                 W4-4 
                 0.116 
               
               
                   
                  976 
                 GT5-3 
                 1.868 
               
               
                   
                  979 
                 GT5-6 
                 8.231 
               
               
                   
                  980 
                 GT5-7 
                 17.135 
               
               
                   
                  984 
                 GT5-11 
                 1.957 
               
               
                   
                  985 
                 GT5-12 
                 19.989 
               
               
                   
                  986 
                 GT5-13 
                 1.332 
               
               
                   
                  987 
                 GT5-14 
                 3.787 
               
               
                   
                  990 
                 GT5-17 
                 2.359 
               
               
                   
                  991 
                 GT5-18 
                 4.255 
               
               
                   
                  993 
                 GT5-20 
                 6.081 
               
               
                   
                 1020 
                 GT9-6 
                 2.655 
               
               
                   
                 1115 
                 GT13-16 
                 7.875 
               
               
                   
                 1123 
                 GT13-24 
                 3.951 
               
               
                   
                 1124 
                 GT13-25 
                 5.511 
               
               
                   
                 1131 
                 GT13-32 
                 2.501 
               
               
                   
                 1132 
                 GT13-33 
                 10.887