SUBSTITUTED BICYCLIC PYRIMIDONE DERIVATIVES
A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: Wherein Y, Z, R1, R2, R3, R4, R5, R6, R7, n, m, and o are as described herein. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.
1 . A compound of formula (III):
or a pharmaceutically acceptable salt thereof
wherein:
m represents 0 or 1; o represents 0 to 2.
R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom;
R3 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
R4 represents a hydrogen atom or a C 1-6 alkyl group;
R5 represents a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C 1-6 alkoxy group;
R6 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom; and
R7 represents a hydrogen atom or a C 1-6 alkyl group.
2 . A pharmaceutical composition comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, according to claim 1 in combination with at least one pharmaceutically acceptable excipient.
3 . A method for the treatment of a disease selected from the group consisting of Alzheimer's disease, Parkinson's disease, taupathies, non-insulin dependent diabetes, obesity, manic depressive illness and schizophrenia, which comprises administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (I):
or a pharmaceutically acceptable salt thereof
wherein:
Y represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a sulfur atom, a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group;
R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, C 3-7 cycloalkyl group, a C 3-7 cycloalkyl-C 1-6 alkyl group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, a C 1-6 alkoxy group optionally substituted by a C 3-5 cycloalkyl group, a C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-6 monoalkylamino group, a C 2-12 dialkylamino group, an acetoxy group or an aminosulfonyl group;
R3 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
R4 represents a hydrogen atom or a C 1-6 alkyl group;
R5 represents a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C 1-6 alkoxy group;
R6 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
R7 represents a hydrogen atom or a C 1-6 alkyl group; and
n represents 0 to 3; m represents 0 to 1; o represents 0 to 2.
4 . The method according to claim 3 where in the compound or salt thereof,
R1 represents an unsubstituted 4-pyridine ring or unsubstituted 4-pyrimidine ring.
5 . The method according to claim 3 where in the compound or salt thereof R1 represents a 3- or 4-pyridine ring or alternatively a 4- or 5-pyrimidine ring;
the rings being optionally substituted by a C 1-2 alkyl group, a C 1-2 alkoxy group or a halogen atom;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-3 alkyl group, C 3-5 cycloalkyl group, a C 3-5 cycloalkyl-C 1-4 alkyl group, a halogen atom, a C 1-3 halogenated alkyl group, a hydroxyl group, a
C 1-3 alkoxy group optionally substituted by a C 3-5 cycloalkyl group, a
C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-3 monoalkylamino group or a C 2-6 dialkylamino group;
R3 represents a hydrogen atom, a C 1-3 alkyl group or a halogen atom;
R4 represents a hydrogen atom or a C 1-3 alkyl group;
R5 represents a hydrogen atom, a C 1-3 alkoxy carbonyl group or a C 1-3 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C 1-3 alkoxy group;
R6 represents a hydrogen atom, a C 1-3 alkyl group or a halogen atom;
R7 represents a hydrogen atom or a C 1-3 alkyl group;
Y represents two hydrogen atoms, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a methylene group optionally substituted by one or two groups chosen from a C 1-3 alkyl group, a hydroxyl group, a C 1-3 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group;
n represents 0 to 3; m represents 0 or 1 and o represents 1 to 2.
6 . The method according to claim 3 where in the compound or salt thereof,
R1 represents an unsubstituted 4-pyridine ring or 4-pyrimidine ring;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-3 alkyl group, a C 1-2 perhalogenated alkyl group, a C 3-4 cycloalkyl group, a C 3-4 cycloalkyl-C 1-3 alkyl group, a halogen atom, a hydroxyl group, a nitro, a cyano, an amino, a C 1-3 alkoxy group optionally substituted by a C 3-4 cycloalkyl group, a C 1-2 perhalogenated alkoxy group or a C 1-3 alkylsulfonyl group;
R3 represents a hydrogen atom or a halogen atom;
R4 represents a hydrogen atom;
R5 represents a hydrogen atom;
R6 represents a hydrogen atom or a C 1-6 alkyl group;
R7 represents a hydrogen atom;
Y represents two hydrogen atoms, or an oxygen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom;
n represents 0 to 1;
m represents 0 to 1 and o represents 1 to 2.
7 . A method for the treatment of a disease selected from the group consisting of Alzheimer's disease, Parkinson's disease, taupathies, non-insulin dependent diabetes, obesity, manic depressive illness and schizophrenia, which comprises administering to a patient in need of said treatment a therapeutically effective amount of a compound of formula (III) or a pharmaceutically acceptable salt thereof according to claim 1 .
8 . The method according to claim 3 wherein the compound or salt thereof is
(+/−)N-(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-phenylacetamide;
(+/−)Phenyl(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)carbamate;
(+/−)N-(4-Fluorophenyl)-N′-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)urea;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-N′-phenylurea;
(+/−)9-[(2-Methoxybenzyl)amino]-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one;
(+/−)3-Fluoro-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Isopropoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Chloro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)3-Cyano-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Chloro-5-fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethyl)benzamide;
(+/−)4-Methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-3-(trifluoromethyl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethyl)benzamide;
(+/−)2-Chloro-4-fluoro-5-nitro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-naphthamide;
(+/−)3-Chloro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2,6-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)3-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Fluoro-6-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Ethoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(3-Bromo-4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-methoxybenzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethoxy)benzamide;
(+/−)2-Isopropoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-(Cyclopropylmethoxy)-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-(Cyclopropylmethoxy)-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-naphthamide;
(+/−)3-Chloro-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-4-trifluoromethyl-benzamide;
(+/−)5-(Ethylsulfonyl)-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2,3-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-{[(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)amino]carbonyl}phenyl acetate;
(+/−)2-Hydroxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-methyl-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)2-Methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-4-trifluoromethyl-benzamide;
(+/−)2-Fluoro-6-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)2-Methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)5-Bromo-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)-4-Dimethylamino-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)-2,4-Dimethoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-(Aminosulfonyl)-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Hydroxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2,4-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-{[(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)amino]carbonyl}phenyl acetate;
(+/−)2,3-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)-5-(trifluoromethoxy)benzamide;
(+/−)2,5-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-{[(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)amino]carbonyl}phenyl acetate;
(+/−)2,4-Dimethoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+)4-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide; and
(−)4-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
9 . A method of inhibiting the activity of glycogen synthase kinase 3-beta (GSK3-β), which comprises administering to a patient in need of said inhibition an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof,
wherein:
Y represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a sulfur atom, a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a hydroxyl group, a C 1-6 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group;
R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, C 3-7 cycloalkyl group, a C 3-7 cycloalkyl-C 1-6 alkyl group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, a C 1-6 alkoxy group optionally substituted by a C 3-5 cycloalkyl group, a C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-6 monoalkylamino group, a C 2-12 dialkylamino group, an acetoxy group or an aminosulfonyl group;
R3 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
R4 represents a hydrogen atom or a C 1-6 alkyl group;
R5 represents a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C 1-6 alkoxy group;
R6 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
R7 represents a hydrogen atom or a C 1-6 alkyl group; and
n represents 0 to 3; m represents 0 to 1; o represents 0 to 2.
10 . The method according to claim 9 where in the compound or salt thereof, R1 represents an unsubstituted 4-pyridine ring or unsubstituted 4-pyrimidine ring.
11 . The method according to claim 9 where in the compound or salt thereof, R1 represents a 3- or 4-pyridine ring or alternatively a 4- or 5-pyrimidine ring; the rings being optionally substituted by a C 1-2 alkyl group, a C 1-2 alkoxy group or a halogen atom;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-3 alkyl group, C 3-5 cycloalkyl group, a C 3-5 cycloalkyl-C 1-4 alkyl group, a halogen atom, a C 1-3 halogenated alkyl group, a hydroxyl group, a
C 1-3 alkoxy group optionally substituted by a C 3-5 cycloalkyl group, a
C 1-2 perhalogenated alkoxy group, a C 1-6 alkylsulfonyl group, a nitro, a cyano, an amino, a C 1-3 monoalkylamino group or a C 2-6 dialkylamino group;
R3 represents a hydrogen atom, a C 1-3 alkyl group or a halogen atom;
R4 represents a hydrogen atom or a C 1-3 alkyl group;
R5 represents a hydrogen atom, a C 1-3 alkoxy carbonyl group or a C 1-3 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C 1-3 alkoxy group;
R6 represents a hydrogen atom, a C 1-3 alkyl group or a halogen atom;
R7 represents a hydrogen atom or a C 1-3 alkyl group;
Y represents two hydrogen atoms, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom or a C 1-3 alkyl group, a methylene group optionally substituted by one or two groups chosen from a C 1-3 alkyl group, a hydroxyl group, a C 1-3 alkoxy group, a C 1-2 perhalogenated alkyl group or an amino group;
n represents 0 to 3; m represents 0 or 1 and o represents 1 to 2.
12 . The method according to claim 9 where in the compound or salt thereof,
R1 represents an unsubstituted 4-pyridine ring or 4-pyrimidine ring;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted by 1 to 4 substituents selected from a C 1-3 alkyl group, a C 1-2 perhalogenated alkyl group, a C 3-4 cycloalkyl group, a C 3-4 cycloalkyl-C 1-3 alkyl group, a halogen atom, a hydroxyl group, a nitro, a cyano, an amino, a C 1-3 alkoxy group optionally substituted by a C 3-4 cycloalkyl group, a C 1-2 perhalogenated alkoxy group or a C 1-3 alkylsulfonyl group;
R3 represents a hydrogen atom or a halogen atom;
R4 represents a hydrogen atom;
R5 represents a hydrogen atom;
R6 represents a hydrogen atom or a C 1-6 alkyl group;
R7 represents a hydrogen atom;
Y represents two hydrogen atoms, or an oxygen atom;
Z represents a bond, an oxygen atom, a nitrogen atom substituted by a hydrogen atom;
n represents 0 to 1;
m represents 0 to 1 and o represents 1 to 2.
13 . A method of inhibiting the activity of glycogen synthase kinase 3-beta (GSK3-β), which comprises administering to a patient in need of said inhibition an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, according to claim 1 .
14 . The method according to claim 9 wherein the compound or salt thereof is
(+/−)N-(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-phenylacetamide;
(+/−)Phenyl(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)carbamate;
(+/−)N-(4-Fluorophenyl)-N′-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)urea;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-N′-phenylurea;
(+/−)9-[(2-Methoxybenzyl)amino]-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one;
(+/−)3-Fluoro-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Isopropoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Chloro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)3-Cyano-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Chloro-5-fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethyl)benzamide;
(+/−)4-Methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-3-(trifluoromethyl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethyl)benzamide;
(+/−)2-Chloro-4-fluoro-5-nitro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-naphthamide;
(+/−)3-Chloro-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2,6-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)3-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Fluoro-6-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Ethoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(3-Bromo-4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-methoxybenzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-(trifluoromethoxy)benzamide;
(+/−)2-Isopropoxy-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-(Cyclopropylmethoxy)-N-(4-oxo-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-(Cyclopropylmethoxy)-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)N-(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-2-naphthamide;
(+/−)3-Chloro-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-4-trifluoromethyl-benzamide;
(+/−)5-(Ethylsulfonyl)-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2,3-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)2-{[(4-Oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)amino]carbonyl}phenyl acetate;
(+/−)2-Hydroxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-methyl-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)2-Methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-4-trifluoromethyl-benzamide;
(+/−)2-Fluoro-6-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)2-Methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)5-Bromo-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)-4-Dimethylamino-2-methoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)-2,4-Dimethoxy-N-(9-methyl-4-oxo-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-9-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidin-8-yl)-benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-5-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-(Aminosulfonyl)-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Hydroxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2,4-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-{[(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)amino]carbonyl}phenyl acetate;
(+/−)2,3-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)-5-(trifluoromethoxy)benzamide;
(+/−)2,5-Dimethoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Bromo-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Fluoro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-Methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)5-Chloro-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)4-Amino-2-methoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+/−)2-{[(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)amino]carbonyl}phenyl acetate;
(+/−)2,4-Dimethoxy-N-(4-oxo-2-pyridin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;
(+)4-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide; and
(−)4-chloro-2-methoxy-N-(4-oxo-2-pyrimidin-4-yl-4,6,7,8,9,10-hexahydropyrimido[1,2-a]azepin-10-yl)benzamide;