1. A compound of formula (I):
wherein
R1 is (CRcRd)m\u2014X \u2014Ra or (CRcRd)n\u2014X \u2014Rb, in which m is 3-5; n is 2-5; X is N(Re),O, or S, or X and Ra or X and Rb, taken together, is heteroaryl; Ra is H, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, heteroaryl, or aryl optionally substituted with OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, C1-C6 alkoxy, aryloxy, heteroaryloxy, heteroaryl, aryl, NO2, CN, COORf, or C(O)Rf, or Ra and X, taken together, is heteroaryl; Rb is H, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, heteroaryl, or aryl optionally substituted with OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryloxy, heteroaryloxy, heteroaryl, aryl, NO2, CN, COORf, or C(O)Rf, or Rb and X, taken together, is heteroaryl; each Rc, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; and each Rd, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; each of Re and Rf, independently, being H, C1-C6 alkyl, aryl, or heteroaryl; each of R2 and R3 is H; and
one of R4, R5,R6, and R7 is OH, C1-C6 alkyl, C3-C15 cycloalkyl, C3\u2014C15 heterocycloalkyl, aryl, heteroaryl, C1-C6 alkoxy, aryloxy, heteroaryloxy, C1-C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg, or C(O)Rg; and each of the others, independently, is H, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, C1-C6 alkoxy, aryloxy, heteroaryloxy, C1-C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1- C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg, or C(O)Rg; each Rg, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; and each Rh, independently, is H or C1-C6 alkyl.
2. The compound of claim 1, wherein Ra is heteroaryl or aryl substituted with C3-C6 alkyl, C1-C6 alkoxy, heteroaryl, C(O)Rf, or NO2, or Ra and X, taken together, is heteroaryl; Rb is heteroaryl; n is 2; each of R2 and R3 is H; and one of R4, R5, R6, and R7 is OH, C1-C6 alkyl, C1-C6 alkoxy, or COORe; and each of the others, independently, is H, C1-C6 alkyl, C1-C6 alkoxy, or C(O)Re.
3. The compound of claim 2, wherein Ra is heteroaryl or aryl substituted with C3-C6 alkyl or C(O)Rf.
4. The compound of claim 3, wherein each Ra, independently, is
5. The compound of claim 3, wherein each of R2 and R3 is H; and one of R4, R5,R6, and R7 is OH, OCH2COOR, OC(CH3)2COOR,
OCH(CH3)COOR, O(CH2)2COOR, O(CH2)3COOR, CH2COOR,COOR,
in which R is H, C1-C6 alkyl, aryl, or heteroaryl
6. The compound of claim 4, wherein each of R2 and R3 are H; and
one of R4, R5,R6, and R7 is OH, OCH2COOR, OC(CH3)2COOR,
OCH(CH3)COOR, O(CH2)2COOR, O(CH2)3COOR, CH2COOR,COOR,
in which R is H, C1-C6 alkyl, aryl, or heteroaryl.
7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising a compound of claim 1 and tetraethylthiuram disulfide.
9. A compound of formula (I):
wherein
R1 is H, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, C(O)Ra, or SO2Ra, in which Ra is C1-C6 alkyl, heteroaryl, or aryl optionally substituted with CF3, OH, halogen, C1-C6 alkoxy, aryloxy, heteroaryloxy, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, NO2, CN, COORb, or C(O)Rb; Rb being H, C1-C6 alkyl, aryl, or heteroaryl;
each of R2 and R3 is H; and
one of R4, R5,R6, R7 is O\u2014(CReRf)m\u2014X\u2014Rc, or O \u2014C(ReRf)Rd; and
each of the others, independently, is H, OH, halogen, C1-C6 alkyl, C3-C15 cycloalkyl, C3\u2014C15 heterocycloalkyl, aryl, heteroaryl, C1-C6 alkoxy, aryloxy, heteroaryloxy, C1-C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg,or C(O)Rg; or one R4, R5, R6, and R7 is, O \u2014(CReRf)n\u2014X \u2014Rc, or O \u2014C(ReRf)Rd; and each of the others, independently, is H, OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3\u2014C15 heterocycloalkyl, aryl, heteroaryl, C3-C6 alkoxy, aryloxy, heteroaryloxy, C1-C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg, or C(O)Rg; in which m is 3-5; n is 2-5; X is O; each Rc, independently, is C1-C6 alkyl, COORj, heteroaryl containing at least two aromatic rings fused together, or aryl optionally substituted with OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3\u2014C15 heterocycloalkyl, C1-C6 alkoxy, aryloxy, heteroaryloxy, heteroaryl, aryl, NO2, CN, COORj, or C(O)Rj; each Rd, independently, is H, OH, halogen, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, C1-C6 alkyl COORj ; each Re, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; each Rf, independently, is H, or C1-C6 alkyl; and each of Rg and Rh, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; each of Ri and Rj, independently, is H, C1-C6 alkyl, aryl, or heteroaryl.
10. The compound of claim 9, wherein R1 is H, C1-C6 alkyl, or SO2Ra; each R2 and R3 is H; one of R4, R5,R6,and R7 is O \u2014(CReCRf)m\u2014X \u2014Rc, or O \u2014C(ReRf)Rd, and each of the others, independently, is H, C1-C6 alkyl, C1-C6 alkoxy, or COORg; or each of R2 and R3 is H and one of R4, R5, R6, and R7 is O \u2014(CReRf)n\u2014X \u2014Rc, and each of the others, independently, is H; n is 2; Rc is heteroaryl containing at least two aromatic rings fused together or aryl substituted with C3-C6 alkyl, heteroaryl, or C(O)Rj; and Rd is COORj.
11. The compound of claim 10, wherein Rc is heteroaryl containing at least two aromatic rings fused together or aryl substituted with C3-C6 alkyl or C(O)Rj.
12. The compound of claim 11, wherein Rc is
13. The compound of claim 11, wherein R1 is H, CH2COOR, CH(CH3)COOR, CH(CH2CH3)COOR, CH2CH2COOR, CH2(CH2)2COOR, or
,in which R is H, C1C6 alkyl, aryl, or heteroaryl.
14. The compound of claim 12,wherein R1 is H, CH2COOR, CH(CH3)COOR, CH(CH2CH3)COOR, CH2CH2COOR, CH2(CH2)2COOR, or
,in which R is H, C1-C6 alkyl, aryl, or heteroaryl.
15. The compound of claim 9, wherein the compound is one of compounds 2, 17, 26-29, 32, 35, 42, 53-55, 57, 58, 60, 69-73, 80-83, 88, 90, 93, 100, 112, 113, 115, 117, 119, 125-129, 131-133, 137-140, 144, 145, 152, 166, 167, and 170-174, or a salt thereof.
16. A pharmaceutical composition comprising a compound of claim 9 and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising a compound of claim 9 and tetraethylthiuram disulfide.
18. A compound of formula (I):
wherein
R1 is C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, heteroaryl, C(O)Ra, SO2Ra, or aryl optionally substituted with OH, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, C1-C6 alkoxy, aryloxy, heteroaryloxy, heteroaryl, aryl, NO2, CN, COORa, or C(O)Ra; in which Ra is C1-C6 alkyl, heteroaryl, or aryl optionally substituted with CF3, OH, halogen, C1-C6 alkoxy, aryloxy, heteroaryloxy, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, NO2, CN, COORb, or C(O)Rb; Rb being H, C1-C6 alkyl, aryl, or heteroaryl;
Each of R2 and R3 is H; and
one of R4, R5,R6, R7 is O \u2014(CReCRf)m\u2014X \u2014Rc, or O \u2014C(ReRf)Rd; and each of the others, independently, is H, OH, halogen, C1-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, C1-C6 alkoxy, aryloxy, heteroaryloxy, C1-C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg, or C(O)Rg; or one R4, R5, R6, and R7 is O \u2014(CReRf)n\u2014X \u2014Rc, or O \u2014C(ReRf)Rd; and each of the others, independently, is H, OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, aryl, heteroaryl, C3-C6 alkoxy, aryloxy, heteroaryloxy, C1, -C6 alkylthio, arylthio, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, NO2, CN, SO3H, SO2N(RgRh), SO2Rg, COORg, or C(O)Rg; in which m is 3-5; n is 2-5; X is O; Rc is C1-C6 alkyl, COORj, heteroaryl, or aryl optionally substituted with OH, halogen, C3-C6 alkyl, C3-C15 cycloalkyl, C3-C15 heterocycloalkyl, C1-C6 alkoxy, aryloxy, heteroaryloxy, heteroaryl, aryl, NO2, CN, COORj, or C(O)Rj; Rd is H, OH, halogen, NH2, C1-C6 alkylamino, C1-C12 dialkylamino, arylamino, diarylamino, C1-C6 alkyl, COORi; each Re, independently, is H, C1-C6 alkyl, aryl, or heteroaryl; each Rf, independently, is H, C1-C6 alkyl, and each Rg is H, C1-C6 alkyl, aryl, or heteroaryl; and each Rh is H, C1C6 alkyl, each Ri is C1-C6 alkyl, aryl, or heteroaryl; each Rj is H, C1-C6 alkyl, aryl, or heteroaryl.
19. The compound of claim 18, wherein R1 is C1-C6 alkyl or SO2Ra; each of R2, and R3 is H; and one of R4, R5, R6, R7 is (CReRf)n\u2014X \u2014Rc or O \u2014(CReRf)n\u2014X \u2014Rc, and each of the others, independently, is H, C1-C6 alkyl, C1-C6 alkoxy, or COORf; and Rc is heteroaryl or aryl substituted with heteroaryl or C(O)Ri.
20. The compound of claim 19, wherein Rc is heteroaryl.
21. The compound of claim 20, wherein Rc is pyridinyl.
22. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising a compound of claim 18 and tetraethylthiuram disulfide.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound represented by formula (I):
wherein R1 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, R1s are same or different, two R1s may together form a cyclic group which may have a substituent(s);
R2, R3, R4, R5, R6 and R7 are each independently a hydrogen atom(s) or a substituent(s), R4 and R5 andor R6 and R7 may form a cyclic group which may have a substituent(s) together with their binding carbon atom;
ring A1 is a monocyclic carbocyclic ring or a monocyclic heterocyclic ring;
ring A2 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, \u2014C(\u2550O)\u2014, \u2014C(\u2550S)\u2014, \u2014C(\u2550O)NR8\u2014, \u2014C(\u2550S)NR8\u2014, \u2014SO2\u2014, \u2014C(\u2550O)O\u2014 or \u2014SO2NR8\u2014 group wherein X binds to a left side of each group,
R8 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 R4 and R5 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 A1 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 A1 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 \u2014C(\u2550O)\u2014 or \u2014C(\u2550O)NR8\u2014 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 andor 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 R1A has the same meaning as R1;
tB is 0 or an integer of 1 to 3, when tB is 2 or more, R1s 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, R1s are same or different;
R4 and R5 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 B2 is C1-8 alkyl which may have a substituent(s);
D is an atom which constitutes ring A and is a carbon atom or a nitrogen atom,
\u2003is 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 A2 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 A2 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 \u03b2-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 R20 is C1-8 alkoxy which may have a substituent(s) or C3-7 cycloalkyl which may have a substituent(s);
R202 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 R201 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);
R202 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\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(2) 2-acetyl-1-(2,4-difluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(3) 2-acetyl-1-(3,4-difluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(4) 2-acetyl-1-(3-fluorophenyl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(5) 2-acetyl-6-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(6) 2-acetyl-1-(2,4-difluorophenyl)-6-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(7) 2-acetyl-1-(3,4-difluorophenyl)-6-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(8) 2-acetyl-1-(3-fluorophenyl)-7-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(9) 2-acetyl-7-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(10) 2-acetyl-1-(3-fluorophenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(11) 1-(2,6-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(12) 1-(3,5-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(13) 1-(2,4-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(14) 1-(2,3-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(15) 1-(2,5-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(16) 1-(3,4-difluorophenyl)-N-(3,5-dimethylphenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(17) 6-chloro-N-(3,5-dimethylphenyl)-1-(3-fluorophenyl)-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(18) N-(3,5-dimethylphenyl)-1-(3-fluorophenyl)-6-methoxy-1,9-dihydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-2(3H)-carboxamide,
(19) 2-acetyl-1-(3-fluorophenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(20) 2-acetyl-1-(2,4-difluorophenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(21) 2-acetyl-1-(2,4-difluorophenyl)-7-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(22) 2-acetyl-1-(3,4-difluorophenyl)-7-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(23) 2-acetyl-5-fluoro-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(24) 2-acetyl-1-(2,4-difluorophenyl)-5-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(25) 2-acetyl-1-(3,4-difluorophenyl)-5-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(26) 2-acetyl-1-(3-fluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(27) 2-acetyl-1-(2,4-difluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(28) 2-acetyl-1-(3,4-difluorophenyl)-8-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(29) 2-acetyl-1-(3-fluorophenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(30) 2-acetyl-1-(3,4-difluorophenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(31) 8-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(3,5-dimethylphenyl)-5,6,8,9-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7-carboxamide,
(32) N-(3,5-dimethylphenyl)-8\u2032-(3-fluorophenyl)-1\u2032,8\u2032-dihydrospirocyclopropane-1,5\u2032-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7\u2032(6\u2032H)-carboxamide,
(33) N-(3,5-dimethylphenyl)-8-(3-fluorophenyl)-9-methyl-5,6,8,9-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7-carboxamide,
(34) N-(3,5-dimethylphenyl)-8-(3-fluorophenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7-carboxamide,
(35) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido3\u2032,4\u2032:4,5pyrrolo2,3-cpyridine-7-carboxamide,
(36) 7-acetyl-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido3\u2032,4\u2032:4,5pyrrolo2,3-cpyridine,
(37) N-(3,5-dimethylphenyl)-8\u2032-(3-fluorophenyl)-1\u2032-methyl-1\u2032,8\u2032-dihydrospirocyclopropane-1,5\u2032-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7\u2032(6\u2032H)-carboxamide,
(38) 7\u2032-acetyl-8\u2032-(3-fluorophenyl)-1\u2032-methyl-1\u2032,6\u2032,7\u2032,8\u2032-tetrahydrospirocyclopropane-1,5\u2032-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine,
(39) N-(3,5-dimethylphenyl)-8-(3-methoxyphenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7-carboxamide,
(40) 8-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(3,5-dimethylphenyl)-1-methyl-1,5,6,8-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo2,3-bpyridine-7-carboxamide,
(41) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-2-methoxy-5,6,8,9-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo3,2-bpyridine-7-carboxamide,
(42) 2-chloro-N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo3,2-bpyridine-7-carboxamide,
(43) N-(3,5-dimethylphenyl)-6-(3-fluorophenyl)-5,6,8,9-tetrahydro-7H-pyrido4\u2032,3\u2032:4,5pyrrolo3,2-bpyridine-7-carboxamide,
(44) 7-acetyl-2-chloro-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido4\u2032,3\u2032:4,5pyrrolo3,2-bpyridine,
(45) 7-acetyl-6-(3-fluorophenyl)-6,7,8,9-tetrahydro-5H-pyrido4\u2032,3\u2032:4,5pyrrolo3,2-bpyridine,
(46) 2-ethyl-1-(3-fluorophenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(47) 2-acetyl-5-fluoro-1-(2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(48) 2-acetyl-5-methoxy-1-(2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane, or
(49) 4-(2-acetyl-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-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\u03b2-carboline-4,1\u2032-cyclopropane,
(2) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(3) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(4) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(5) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(6) 2-acetyl-5-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(7) 2-acetyl-5-chloro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(8) 2-acetyl-5-fluoro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(9) 2-acetyl-6-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(10) 2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(11) 2-acetyl-1-(5-fluoro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(12) 2-acetyl-1-(4-fluoro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(13) 2-acetyl-1-(2,4-dimethoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane
(14) 2-acetyl-1-(2-fluoro-6-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(15) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(16) 2-acetyl-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(17) 2-acetyl-5-fluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(18) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(19) 2-acetyl-1-(4-fluoro-2-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(20) 2-acetyl-6-methoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(21) 2-acetyl-1-(2-fluoro-6-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(22) 2-acetyl-6,7-dimethoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(23) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(24) 2-acetyl-1-(2-methoxy-4-methylphenyl)-5-methyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(25) 2-acetyl-1-(2,3-dihydro-1-benzofuran-7-yl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(26) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-5-methyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(27) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(28) (1S)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(29) (\u2212)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(30) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,6-difluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(31) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(32) (+)-2-acetyl-1-(2-fluoro-6-methoxyphenyl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(33) (+)-2-acetyl-5-fluoro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(34) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,7-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(35) 2-acetyl-5-chloro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(36) 2-acetyl-5,6-difluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(37) 2-acetyl-5,6-difluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(38) 2-acetyl-5-chloro-1-(2-fluoro-6-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(39) 2-acetyl-1-(4-chloro-2-isopropoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(40) 2-acetyl-1-4-chloro-2-(cyclopentyloxy)phenyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(41) 4-(2-acetyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-1-yl)-3-methoxybenzonitrile,
(42) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5,7-difluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(43) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-8-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(44) 4-(2-acetyl-5-fluoro-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane-1-yl)-3-methoxybenzonitrile,
(45) 2-acetyl-5,6-dimethoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(46) 2-acetyl-1-(2,3-dihydro-1-benzofuran-7-yl)-5-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(47) 2-acetyl-5-methoxy-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(48) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-6,8-dimethoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(49) 2-acetyl-6-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(50) 2-acetyl-1-(4-chloro-2-methoxyphenyl)-5-fluoro-8-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(51) 2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-8-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(52) (+)-2-acetyl-1-(2-fluoro-6-methoxyphenyl)-6-methoxy-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(53) (+)-2-acetyl-1-(2-methoxy-4-methylphenyl)-5-methyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(54) (+)-2-acetyl-1-(4-chloro-2-methoxyphenyl)-6-methoxy-5-methyl-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(55) (+)-2-acetyl-5-fluoro-1-(4-fluoro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane,
(56) (+)-2-acetyl-5,6-difluoro-1-(2-methoxy-4-methylphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-cyclopropane, or
(57) (+)-2-acetyl-5-chloro-1-(4-chloro-2-methoxyphenyl)-1,2,3,9-tetrahydrospiro\u03b2-carboline-4,1\u2032-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 andor 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 andor 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.