Tricyclic compound and use thereof

Abstract

The present invention relates to the compound represented by formula (I): (wherein, all the symbols have the same meaning as that of the specification), a salt thereof, a solvate thereof or a prodrug thereof. Since the compound of the present invention has an anti stress action, it is useful for preventive and/or therapeutic agent for a disease caused by stress, especially a digestive system disease caused by stress and is superior to oral absorption.

1 . A compound represented by formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is a hydrogen atom(s) or a substituent(s), 
         t is 0 or an integer of 1 to 8, when t is 2 or more, R 1 s are same or different, two R 1 s may together form a cyclic group which may have a substituent(s); 
         R 2 , R 3 , R 4 , R 5 , R 6  and R 7  are each independently a hydrogen atom(s) or a substituent(s), R 4  and R 5  and/or R 6  and R 7  may form a cyclic group which may have a substituent(s) together with their binding carbon atom; 
         ring A 1  is a monocyclic carbocyclic ring or a monocyclic heterocyclic ring; 
         ring A 2  is a cyclic group which may have a substituent(s); 
         B is a hydrogen atom, a hydrocarbon group which may have a substituent(s) or a cyclic group which may have a substituent(s); 
         X and Z are each independently a bond, C1-3 alkylene which may have a substituent(s), C2-3 alkenylene which may have a substituent(s) or C2-3 alkynylene which may have a substituent(s); 
         Y is a bond, —C(═O)—, —C(═S)—, —C(═O)NR 8 —, —C(═S)NR 8 —, —SO 2 —, —C(═O)O— or —SO 2 NR— group wherein X binds to a left side of each group, 
         R 8  is a hydrogen atom or a substituent; 
         m is 0 or 1; 
            is a single bond or a double bond wherein 1) a and b are not a double bond at the same time, 2) when m is 0, b is a double bond, 3) when m is 1, b is a single bond, 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         2 . The compound according to  claim 1 , wherein R 4  and R 5  form a cyclic group which may have a substituent(s) together with their binding carbon atom, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         3 . The compound according to  claim 1 , wherein ring A 1  is a monocyclic heterocyclic ring, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         4 . The compound according to  claim 1 , wherein ring A 1  is a monocyclic carbocyclic ring, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         5 . The compound according to  claim 1 , wherein X is a bond, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         6 . The compound according to  claim 1 , wherein Y is —C(═O)— or —C(═O)NR 8 — wherein X binds to a left side of each group, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         7 . The compound according to  claim 1 , wherein Z is a bond or C1-3 alkylene which may have a substituent(s), a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         8 . The compound according to  claim 1 , wherein B is C1-8 alkyl which may have a substituent(s), C3-10 monocyclic or bicyclic aromatic carbocyclic which may have a substituent(s), a carbocyclic ring which is partially or fully saturated, or 3-10 membered monocyclic or bicyclic aromatic heterocyclic ring which may be partially or fully saturated, and which contains 1 to 4 hetero atom(s) selected from an oxygen atom, a nitrogen atom and/or a sulfur atom, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         9 . The compound according to  claim 1 , which is a compound represented by formula (I-A): 
       
         
           
           
               
               
           
         
       
       wherein all the symbols have the same meanings as described in  claim 1 , a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         10 . The compound according to  claim 9 , which is a compound represented by formula (I-A-1): 
       
         
           
           
               
               
           
         
         wherein R IA  has the same meaning as R 1 ; 
         tB is 0 or an integer of 1 to 3, when tB is 2 or more, R 1 s are same or different; 
         other symbols have the same meanings as described in  claim 1 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         11 . The compound according to  claim 1 , which is a compound represented by formula (I-B-1): 
       
         
           
           
               
               
           
         
         wherein tA is 0 or an integer of 1 to 4, when tA is 2 or more, R 1 s are same or different; 
         R 4  and R 5  form cyclic group which may have a substituent(s) together with their binding carbon atom; 
         other symbols have the same meanings as described in  claim 1 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         12 . The compound according to  claim 1 , which is a compound represented by formula (I-B-2): 
       
         
           
           
               
               
           
         
         wherein all symbols have the same meaning as described in  claim 1  or  10 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         13 . The compound according to  claim 11 , which is a compound represented by formula (I-B-1-1): 
       
         
           
           
               
               
           
         
         wherein B is C1-8 alkyl which may have a substituent(s); 
         D is an atom which constitutes ring A 2  and is a carbon atom or a nitrogen atom, 
       
       
         
           
           
               
               
           
         
       
       is a cyclic group which has at least two same or different substituents;
 other symbols have the same meanings as described in  claim 1  or  11 , a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
 
     
     
         14 . The compound according to  claim 13 , wherein 
       
         
           
           
               
               
           
         
       
       is a cyclic group which has two same or different substituents, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         15 . The compound according to  claim 14 ,
 wherein one substituent on ring A 2  is (1) C1-8 alkoxy which may have a substituent(s), or (2) C3-7 cycloalkyloxy which may have a substituent(s);   the other substituent is selected from (1) a halogen atom, (2) cyano, (3) C1-8 alkyl which may have a substituent(s) and (4) C1-8 alkoxy which may have a substituent(s),   a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.   
     
     
         16 . The compound according to  claim 15 ,
 wherein one substituent on ring A 2  is selected from (1) methoxy which may have a fluorine atom(s), (2) isopropoxy which may have a fluorine atom(s), (3) cyclopentyloxy which may have a fluorine atom(s);   the other substituent is selected from (1) a fluorine atom, (2) a chlorine atom, (3) cyano, (4) methyl, and (5) methoxy which may have a fluorine atom(s),   a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.   
     
     
         17 . The compound according to  claim 14 , wherein the cyclic group represented by 
       
         
           
           
               
               
           
         
       
       is a benzene ring, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         18 . The compound according to  claim 13 , wherein one substituent is substituted to an atom neighboring D, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         19 . The compound according to  claim 13 , which is a compound represented by formula (I-B-1-1-a): 
       
         
           
           
               
               
           
         
         wherein   is β-configuration and other symbols have the same meanings as described in  claim 13 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         20 . The compound according to  claim 14 , which is a compound represented by formula (I-B-1-2): 
       
         
           
           
               
               
           
         
         wherein R 201  is C1-8 alkoxy which may have a substituent(s) or C3-7 cycloalkyl which may have a substituent(s); 
         R 202  is a halogen atom, cyano, C1-8 alkyl which may have a substituent(s) or C1-8 alkoxy which may have a substituent(s); 
         other symbols have the same meanings as described in  claim 11 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         21 . The compound according to  claim 20 , which is a compound represented by formula (I-B-1-2-a): 
       
         
           
           
               
               
           
         
         wherein all symbols have the same meanings as described in  claim 11 ,  19  or  20 , 
         a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
       
     
     
         22 . The compound according to  claim 20  or  21 ,
 wherein R 201  is selected from (1) methoxy which may have a fluorine atom(s), (2) isopropoxy which may have a fluorine atom(s), and (3) cyclopentyloxy which may have a fluorine atom(s); 
 R 202  is selected from (1) a fluorine atom, (2) a chlorine atom, (3) cyano, (4) methyl, and (5) methoxy which may have a fluorine atom(s), 
 a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
 
     
     
         23 . The compound according to  claim 1 , which is
 (1) 1-(1,3-benzodioxol-5-yl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (2) 2-acetyl-1-(2,4-difluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (3) 2-acetyl-1-(3,4-difluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (4) 2-acetyl-1-(3-fluorophenyl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (5) 2-acetyl-6-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (6) 2-acetyl-1-(2,4-difluorophenyl)-6-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (7) 2-acetyl-1-(3,4-difluorophenyl)-6-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (8) 2-acetyl-1-(3-fluorophenyl)-7-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (9) 2-acetyl-7-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (10) 2-acetyl-1-(3-fluorophenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (11) 1-(2,6-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (12) 1-(3,5-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (13) 1-(2,4-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (14) 1-(2,3-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (15) 1-(2,5-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (16) 1-(3,4-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (17) 6-chloro-N-(3,5-dimethylphenyl)-1-(3-fluorophenyl)-1,9-dihydrospiro[β-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (18) N-(3,5-dimethylphenyl)-1-(3-fluorophenyl)-6-methoxy-1,9-dihydrospiro[3-carboline-4,1′-cyclopropane]-2(3H)-carboxamide,   (19) 2-acetyl-1-(3-fluorophenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (20) 2-acetyl-1-(2,4-difluorophenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (21) 2-acetyl-1-(2,4-difluorophenyl)-7-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (22) 2-acetyl-1-(3,4-difluorophenyl)-7-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (23) 2-acetyl-5-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (24) 2-acetyl-1-(2,4-difluorophenyl)-5-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (25) 2-acetyl-1-(3,4-difluorophenyl)-5-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (26) 2-acetyl-1-(3-fluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (27) 2-acetyl-1-(2,4-difluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (28) 2-acetyl-1-(3,4-difluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (29) 2-acetyl-1-(3-fluorophenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (30) 2-acetyl-1-(3,4-difluorophenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (31) 8-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(3,5-dimethylphenyl)-5,6,8,9-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine-7-carboxamide,   (32) N-(3,5-dimethylphenyl)-8′-(3-fluorophenyl)-1′,8′-dihydrospiro[cyclopropane-1,5′-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine]-7′(6′H)-carboxamide,   (33) N-(3,5-dimethylphenyl)-8-(3-fluorophenyl)-9-methyl-5,6,8,9-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine-7-carboxamide,   (34) N-(3,5-dimethylphenyl)-8-(3-fluorophenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine-7-carboxamide,   (35) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido[3′,4′:4,5]pyrrolo[2,3-c]pyridine-7-carboxamide,   (36) 7-acetyl-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido[3′,4′:4,5]pyrrolo[2,3-c]pyridine,   (37) N-(3,5-dimethylphenyl)-8′-(3-fluorophenyl)-1′-methyl-1′,8′-dihydrospiro[cyclopropane-1,5′-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine]-7′(6′H)-carboxamide,   (38) 7′-acetyl-8′-(3-fluorophenyl)-1′-methyl-1′,6′,7′,8′-tetrahydrospiro[cyclopropane-1,5′-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine,   (39) N-(3,5-dimethylphenyl)-8-(3-methoxyphenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine-7-carboxamide,   (40) 8-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(3,5-dimethylphenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine-7-carboxamide,   (41) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-2-methoxy-5,6,8,9-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[3,2-b]pyridine-7-carboxamide,   (42) 2-chloro-N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[3,2-b]pyridine-7-carboxamide,   (43) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido[4′,3′:4,5]pyrrolo[3,2-b]pyridine-7-carboxamide,   (44) 7-acetyl-2-chloro-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido[4′,3′:4,5]pyrrolo[3,2-b]pyridine,   (45) 7-acetyl-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido[4′,3′:4,5]pyrrolo[3,2-b]pyridine,   (46) 2-ethyl-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (47) 2-acetyl-5-fluoro-1-(2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (48) 2-acetyl-5-methoxy-1-(2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane], or   (49) 4-(2-acetyl-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane]-1-yl)benzonitrile,   a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.   
     
     
         24 . The compound according to  claim 13 , which is
 (1) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (2) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (3) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (4) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (5) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (6) 2-acetyl-5-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (7) 2-acetyl-5-chloro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (8) 2-acetyl-5-fluoro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (9) 2-acetyl-6-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (10) 2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (11) 2-acetyl-1-(5-fluoro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (12) 2-acetyl-1-(4-fluoro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (13) 2-acetyl-1-(2,4-dimethoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane](14) 2-acetyl-1-(2-fluoro-6-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (15) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (16) 2-acetyl-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (17) 2-acetyl-5-fluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (18) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (19) 2-acetyl-1-(4-fluoro-2-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (20) 2-acetyl-6-methoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (21) 2-acetyl-1-(2-fluoro-6-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (22) 2-acetyl-6,7-dimethoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (23) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (24) 2-acetyl-1-(2-methoxy-4-methylphenyl)-5-methyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (25) 2-acetyl-1-(2,3-dihydro-1-benzofuran-7-yl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (26) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-5-methyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (27) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (28) (1S)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (29) (−)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (30) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (31) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (32) (+)-2-acetyl-1-(2-fluoro-6-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (33) (+)-2-acetyl-5-fluoro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (34) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro[f-carboline-4,1′-cyclopropane],   (35) 2-acetyl-5-chloro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (36) 2-acetyl-5,6-difluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (37) 2-acetyl-5,6-difluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (38) 2-acetyl-5-chloro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (39) 2-acetyl-1-(4-chloro-2-isopropoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (40) 2-acetyl-1-[4-chloro-2-(cyclopentyloxy)phenyl]-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (41) 4-(2-acetyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane]-1-yl)-3-methoxybenzonitrile,   (42) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,7-difluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (43) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-8-fluoro-1,2,3,9-tetrahydrospiro[f-carboline-4,1′-cyclopropane],   (44) 4-(2-acetyl-5-fluoro-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane]-1-yl)-3-methoxybenzonitrile,   (45) 2-acetyl-5,6-dimethoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (46) 2-acetyl-1-(2,3-dihydro-1-benzofuran-7-yl)-5-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (47) 2-acetyl-5-methoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (48) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (49) 2-acetyl-6-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (50) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-8-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (51) 2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-8-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (52) (+)-2-acetyl-1-(2-fluoro-6-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (53) (+)-2-acetyl-1-(2-methoxy-4-methylphenyl)-5-methyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (54) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-5-methyl-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (55) (+)-2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   (56) (+)-2-acetyl-5,6-difluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane], or   (57) (+)-2-acetyl-5-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro[β-carboline-4,1′-cyclopropane],   a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof.   
     
     
         25 . A pharmaceutical composition comprising the compound represented by formula (I) described in  claim 1 , a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. 
     
     
         26 . The pharmaceutical composition according to  claim 25 , which is an agent for preventing and/or treating a disease caused by stress. 
     
     
         27 . The pharmaceutical composition according to  claim 26 , wherein the disease caused by stress is a digestive system disease caused by stress. 
     
     
         28 . The pharmaceutical composition according to  claim 27 , wherein the digestive system disease caused by stress is irritable bowel syndrome, ulcerative colitis, or Crohn's disease. 
     
     
         29 . A pharmaceutical composition comprising the compound represented by formula (I) described in  claim 1 , a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof and one or more kind of agents selected from an antianxiety, an antidepressant, an anticholinergic, a gastrointestinal tract function regulator, a gastrointestinal tract prokinetic drug, an antidiarrheal, an evacuant, a calcium antagonist, a phosphodiesterase inhibitor and a serotonin antagonist in combination. 
     
     
         30 . A method for preventing and/or treating a disease caused by stress in a mammal comprising administering an effective amount of the compound represented by formula (I) described in  claim 1 , a salt thereof, an N-oxide, a solvate or a prodrug thereof to the mammal. 
     
     
         31 . Use of the compound represented by formula (I) according to  claim 1 , a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof for preparing an agent for preventing and/or treating a disease caused by stress.