Patent EA-004507-B1 (EA)
Title: Novel spiro compounds
Inventor: FUKAMI TAKEHIRO
IPC: C07D471/10
Filed: 2000-08-11
Abstract: 1. A compound represented by the general formula (I): wherein Ar<1> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, triazinyl, benzoxazolyl, benzothiazolyl, quinolyl or pyrido [3,2-b] pyridyl and said substituent is selected from the group consisting of: halogen, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, C2-6alkenyl, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl, C2-6alkylene optionally substituted with an oxo group, and a group represented by formula of -Q-Ar<2>; Ar<2> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, quinolyl, pyridyl, imidazolyl and benzofuranyl, the substituent is selected from the group consisting of halogen, cyano, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, hydroxy, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl; n represents 0 or 1; Q represents a single bond or carbonyl; T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, C1-6alkyl and hydroxy, where at least three of them represent the said methine group; X represents methine or nitrogen; Y represents imino which may be substituted with C1-6alkyl or oxygen; a salt or ester thereof. 2. The compound of Claim 1, wherein the aryl in Ar<1> is phenyl. 3. The compound of Claim 1, wherein the heteroaryl in Ar<1> is pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, 1,2,3-triazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, 1,2,4-triazinyl, benzoxazolyl, benzothiazolyl, quinolyl or pyrido [3,2-b] pyridyl. 4. The compound of Claim 1, wherein T, U, V and W are independently methine which may have a substituent selected from the group consisting of halogen, C1-6alkyl, hydroxy and C1-6alkoxy. 5. The compound of Claim 4, wherein T, U, V and W are independently methine which may be substituted with halogen. 6. The compound of Claim 1, wherein one of T, U, V and W is nitrogen. 7. The compound of Claim 1, wherein Y is unsubstituted imino or oxygen. 8. The compound of Claim 1, wherein Y is oxygen. 9. The compound of Claim 1 which is represented by the general formula (I-a): wherein Ar<1> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, triazinyl, benzoxazolyl, benzothiazolyl, quinolyl or pyrido [3,2-b] pyridyl and said substituent is selected from the group consisting of: halogen, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, C2-6alkenyl, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl, C2-6alkylene optionally substituted with an oxo group, and a group represented by formula of -Q-Ar<2>; Ar<2> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, quinolyl, pyridyl, imidazolyl and benzofuranyl, the substituent is selected from the group consisting of halogen, cyano, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, hydroxy, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl; Q represents a single bond or carbonyl; R<1> represents hydrogen or halogen, 10. The compound of Claim 9, wherein the aryl in Ar<1> is phenyl. 11. The compound of Claim 9, wherein the heteroaryl in Ar<1> is imidazolyl, pyrazolyl, isoxazolyl, 1,2,4-thiadiazolyl, pyrazinyl, pyrimidinyl, quinolyl or pyrido[3,2-b] pyridyl. 12. The compound of Claim 1 which is represented by the general formula (I-b): wherein Ar<1> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, triazinyl, benzoxazolyl, benzothiazolyl, quinolyl or pyrido [3,2-b] pyridyl and said substituent is selected from the group consisting of: halogen, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, C2-6alkenyl, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl, C2-6alkylene optionally substituted with an oxo group, and a group represented by formula of -Q-Ar<2>; Ar<2> represents aryl or heteroaryl which may be substituted, the substituent being selected from the group consisting of phenyl, quinolyl, pyridyl, imidazolyl and benzofuranyl, the substituent is selected from the group consisting of halogen, cyano, C1-6alkyl, halo-C1-6alkyl, hydroxy-C1-6alkyl, hydroxy, C1-6alkoxy, halo-C1-6alkoxy, C2-7alkanoyl; Q represents a single bond or carbonyl; T, U, V and W represent independently nitrogen atom or methine group which may have a substituent selected from the group consisting of halogen, C1-6alkyl, hydroxy and C1-6alkoxy, where at least three of them represent the said methine group. 13. The compound of Claim 12, wherein the aryl in Ar<1> is phenyl. 14. The compound of Claim 12, wherein the heteroaryl in Ar<1> is pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, 1,2,3-triazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl or 1,2,4-triazinyl. 15. The compound of Claim 12, wherein one of T, U, V and W is nitrogen. 16. The compound of Claim 12, wherein V is nitrogen and each of T, U and W is unsubstituted methine group. 17. The compound of claim 1, which is N-(4-benzoylphenyl)-3-oxospiro [isoindoline-1,4'-piperidine]-1'-carboxamide, 3-oxo-N-(5-phenyl-2-pyrazinyl) spiro [isoindoline-1,4'-piperidine]-1'-carboxamide, N-(7-methyl-2-quinolyl)-3-oxospiro [isoindoline-1,4'-piperidine]-1'-carboxamide, N-(4-benzoylphenyl)-2-methyl-3-oxospiro [isoindolin-1,4'-piperidine]-1'-carboxamide, N-(4-benzoylphenyl)-3,4-dihydro-3-oxospiro [isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, 3,4-dihydro-3-oxo-N-(5-phenyl-2-pyrazinyl) spiro[isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, 3,4-dihydro-N-(7-methyl-2-quinolyl)-3oxospiro [isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, N-(4-acetylphenyl)-3,4-dihydro-3-oxospiro[isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, 3,4-dihydro-3-oxo-N-[1-(2-quinolyl)-4-imidazolyl]spiro[isoquinoline-1(2H),4'-piperidine]-1'-carboxamide, 3,4-dihydro-N-[5-(2-methyl-1-propenyl)-2-pyrazinyl]-3oxospiro[isoquinoline-1 (2H), 4'-piperidine]1'-carboxamide, 3,4-dihydro-3-oxo-N-(3-phenyl-5-isoxazolyl) spiro [isoquinoline-1 (2H), 4'-piperidine]-1'-carboxamide, N-[1-(7-benzo[b]furanyl)-4-imidazolyl]-3,4-dihydro-3oxospiro[isoquinoline-1 (2H), 4'-piperidine]-1'-carboxamide, N-[1-(3-difluoromethoxyphenyl)-4-imidazolyl]-3,4-dihydro-3-oxospiro [isoquinoline-1 (2H), 4'-piperidine]-1'-carboxamide, 3,4-dihydro-3-oxo-N-[4-(2-pyridylcarbonyl) phenyl] spiro [isoquinoline-1 (2H), 4 piperidine]-1'-carboxamide, N-(3,4-dichlorophenyl)-3,4-dihydro-3-oxospiro [isoquinoline-1 (2H), 4'-piperidine]-1'-carboxamide, N-[1-(3-chlorophenyl)-4-imidazolyl]-3,4-dihydro-3-oxospiro [isoquinoline-1 (2H), 4'-piperidine]1'-carboxamide, 3,4-dihydro-3-oxo-N-(5-phenyl-2-thiazolyl) spiro [isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, 3,4-dihydro-3-oxo-N-[5-(2-pyridyl)-2-pyrazinyl]spiro[isoquinoline-1(2H),4'piperidine]-1'-carboxamide, 3,4-dihydro-N-(4-methyl-2-benzothiazolyl)-3-oxospiro [isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, N-(5-chloro-2-benzoxazolyl)-3,4-dihydro-3-oxospiro [isoquinoline-1 (2H),4'-piperidine]-1'-carboxamide, N-(4-benzoylphenyl)-3-oxospiro [isobenzofuran-1 (3H), 4'piperidine]-1'-carboxamide, 3-oxo-N-(5-phenyl-2-pyrazinyl)-spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, N-(7-methyl-2-quinolyl)-3-oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-(3-phenyl-5-isoxazolyl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-(7-trifluoromethylpyrido [3,2-b] pyridin-2-yl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-(5-phenyl-2-pyrimidinyl)spiro[isobenzofuran1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-[1-(3-quinolyl)-4-imidazolyl]spiro[isobenzofuran-1(3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-(5-phenyl-3-pyrazolyl) spiro [isobenzofuran1 (3H),4'-piperidine]-1'-carboxamide, N-[5-(4-chlorophenyl)-3-pyrazolyl]-3-oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-[5-(3-quinolyl)-3-pyrazolyl] spiro [isobenzofuran1 (3H),4'-piperidine]-1'-carboxamide, N-[5-(3-fluorophenyl)-2-pyrimidinyl]-3-oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-[5-(3-trifluoromethylphenyl)-2-pyrimidinyl]spiro[isobenzofuran-1(3H),4'-piperidine]-1'carboxamide, N-[5-(3-chlorophenyl)-2-pyrimidinyl]-3-oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, N-(7-difluoromethoxypyrido [3,2-b] pyridin-2-yl)-3oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 3-oxo-N-(5-phenyl-1,2,4-thiadiazol-3-yl) spiro [isobenzofuran-1 (3H), 4'-piperidine]-1'-carboxamide, N-{1-[3-(2-hydroxyethyl)phenyl]-4-imidazoly]-3oxospiro [isobenzofuran-1 (3H), 4'-piperidine]-1'carboxamide, N-[4-(1-ethyl-2-imidazolyl)phenyl]-3 oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, N-[1-(3-methoxyphenyl)-4-imidazolyl]-3 oxospiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 6-fluoro-3-oxo-N-(5-phenyl-2-pyrazinyl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 6-fluoro-3-oxo-N-(5-phenyl-2-pyrimidinyl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 5-fluoro-3-oxo-N-(5-phenyl-2-pyrazinyl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, 5-fluoro-3-oxo-N-(5-phenyl-2-pyrimidinyl) spiro [isobenzofuran-1 (3H),4'-piperidine]-1'-carboxamide, N-(4-benzoylphenyl)-3, 4-dihydro-3-oxospiro [1H-2benzopyran-1,4'-piperidine]-1'-carboxamide, 3,4-dihydro-3-oxo-N-(5-phenyl-2-pyrazinyl)spiro[1H-2benzopyran-1,4'-piperidine]-1'-carboxamie, N-(5-benzoyl-2-pyrazinyl)-3,4-dihydro-3-oxospiro [1H-2-benzopyran-1,4'-piperidine]-1'-carboxamide, trans-N-(4-benzoylphenyl)-3'-oxospiro [cyclohexane-1,1' (3'H)-isobenzofuran]-4-ca