Substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo [1,2-a]pyrimidin-5(1H)one derivatives for neurodegenerative disorders
View Patent ↗The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a C 1-6 alkyl group optionally substituted by a C 6,10 aryloxy or a C 6,10 arylamino group; a C 3-6 cycloalkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represents each independently a hydrogen atom, C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom. 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 GSK3β3 or GSK3β3 and cdk5/p25, such as Alzheimer disease.
1. A pyrimidone represented by formula (I) or a salt thereof:
wherein:
X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom;
Y represents a covalent single bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally substituted by a C 1-6 alkyl group, a phenyl or a benzyl group; or a methylene group optionally substituted by one or two groups chosen from a C 1-6 alkyl group, a benzyl group, a hydroxy group, a C 1-4 alkoxy group, a C3-6 cycloalkylmethyloxy, a C 1-2 perhalogenated alkyl group, an amino group, an acetylamino group or a phenyl group;
R1 represents a pyrimidine ring optionally substituted by a C 3-6 cycloalkyl groups a C 1-4 alkyl group, a C 1-4 alkoxy group, a benzyl group or a halogen atom;
when Y represents a covalent single bond, a methylene group optionally substituted or a carbonyl group then R2 represents a C 1-6 alkyl group optionally substituted by a C 6,10 aryloxy or a C 6,10 arylarruno group; a C 3-6 cycloalkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a methylendioxy group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxy group, a C 1-4 alkoxy group, a nitro, a cyano, an amino, a C 1-5 monoalkylamino group, a C 2-10 dialkylamino group, a C 1-6 alkylcarbonylamino group, a C 6,10 arylcarbonylamino group, a C 1-4 alkylsulfonyl group, C 1-4 alkylsulfonyloxy group or a phenyl group;
when Y represents an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted then R2 represents a C 1-6 alkyl group (optionally substituted by a C 6,10 aryloxy or a C 6,10 arylamino group), a C 3-6 cycloalkyl group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; the benzyl group or the rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a methylendioxy group, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxy group, a C 1-4 alkoxy group, a nitro, a cyano, an amino, a C 1-5 monoalkylamino group, a C 2-10 dialkylamino group, a C 1-6 alkylcarbonylamino group, a C 6,10 arylcarbonylamino group, a C 1-4 alkylsulfonyl group, C 1-4 alkylsulfonyloxy group or a phenyl group;
R3 and R4 represent each independently a hydrogen atom, C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom;
R5 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom;
when m equals 0, p equals 1, 2 or 3,
when m equals 1, p equals 0, 1 or 2,
when m equals 2, p equals 0 or 1;
and n represents 0 to 3.
2. A pyrimidone of formula (I) or a salt thereof, according to claim 1 , wherein R1 represents an unsubstituted 4-pyrimidine ring.
3. A pyriniidone of formula (I) which is selected from the group consisting of:
9-(3-Phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Phenylsulfanyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(3-Hydroxy-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(3-Oxo-3-phenyl-propyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(R)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(S)-Hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(1-Methyl-2-oxo-2-phenyl-ethyl)2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Hydroxy-1-methyl-2-phenyl-ethyl)2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2(R)-hydroxy-ethyl]2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Difluoro-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(S)-Hydroxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
3-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
3-Chloro-9-(2(S)-hydroxy-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2(S)-Hydroxy-2-phenyl-ethyl)-3-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Oxo-2-(5,5,8,8-tetramethyl-5,6,7,8 ,tetrahydro-naphthalen-2-yl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahycLro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Naphthalen-2-yl-2-oxo-ethy)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Biphenyl-4-yl-2-oxo-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a]pyrimidin-4-one
9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(7-Methoxy-benzo-[1 ,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8,-tetrahydro-naphthalen-2-yl)-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-7,7,-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Biphenyl-4-yl-2-oxo-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-(2-naphthalen-2-yl-2-oxo-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Hydroxy-2-(7-methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Hydroxy-2-phenyl-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Methoxy- phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Methoxy- phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Hydroxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(S)-Cyclopropylmethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyriinidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-2-ethoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a]pyrimidin-4-one
9-[2-(3-Phenyl-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(S)-Ethoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Ethoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Hydroxy-2-(2-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Chloro-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-(Benzo-[1,3]dioxol-5-yl)-2-hydroxy-propyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Hydroxy-2-(3-methoxy-phenyl)-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-phenyl)-2-hydroxy-propyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyriirnidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
4-[2-(3,3-Dimethyl-6-oxo-8-pyrimidin-4-yl-3 ,4,dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)ethyl]benzonitrile
9-[2-(4-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3,4-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-o-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-2-(pyrimidin-4-yl)-9-(2-p-tolyl-ethyl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-2-hydroxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-2-oxo-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1 ,2-a]pyrimidin-4-one
9-[2-(2-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,4-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Bromo-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Ethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Cyclohexyl-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Nitro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Trifluoromethyl-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-Methoxy-2-(2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(R)-Methoxy-2-phenyl-ethyl)-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-(2-phenyl-ethyl)-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Chloro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2-methoxy-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,6-Dichloro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-9-(2-naphthalen-1-yl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,6-Dimethoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2-trifluoromethoxy-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,4-Dichloro-5-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
7,7-Dimethyl-2-(pyrimidin-4-yl)-9-[2-(2,4,5-trifluoro-phenyl)-ethyl]-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,4-Difluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-Indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
3-Chloro-9-indan-2-ylmethyl-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2-Ethoxy-4-fluoro-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-isopropoxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-hydroxy-phenyl)-ethyl]-7,7-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one or a salt thereof.
4. A pyrimidone of formula (I) which is selected from the group consisting of:
1-(3-Phenyl-propyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2a]pyrimidin-5-one
1-[3-(2-Fluoro-phenyl)-propyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-(2-Oxo-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-(2-Hydroxy-2-phenyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-[2-(7-Methoxy-benzo-[1,3]dioxol-5-yl)-1-methyl-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-(2-Biphenyl-4-yl-2-oxo-ethyl)-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
2,2-Dimethyl-1-(2-oxo-2-p-tolyl-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
2,2-Dimethyl-1-(2-naphthalen-2-yl-2-oxo-ethyl)-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one
1-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-2,2-dimethyl-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1 ,2-a]pyrimidin-5-one; and
2,2-Dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)ethyl]-7-pyrimidin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one;
or a salt thereof.
5. A pyrimidone of formula (I) which is selected from the group consisting of:
9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-2-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Fluoro-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
8-Methyl-9-(2-oxo-2-phenyl-ethyl)-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(2-Methoxy-phenyl)-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2(S)-Hydroxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2(R)-Methoxy-2-phenyl-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(2,5-Dimethoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8-Methyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2(S)-Hydroxy-2-phenyl-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8-Methyl-9-[naphthalene-2-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2(R)-Hydroxy-2-phenyl-ethyll-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(4-Fluoro-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8,8-Dimethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3-Chloro-phenyl)-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8,8-Dimethyl-9-[naphthalen-1-ylmethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8-Ethyl-9-[2-oxo-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(4-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8-Ethyl-9-[2(S)-hydroxy-2-phenyl-ethyl]-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2(S)-Hydroxy-2-(4-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2a]pyrimidin-4-one;
9-[2-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(2,4-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3-Bromo-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-Benzo[1,3]dioxol-5-yl-2-oxo-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-2-(3,5-Dichloro-phenyl)-2-hydroxy-ethyl]-8-methyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Fluoro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2(S)-Hydroxy-2-naphthalen-2-ybethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-(2-Biphenyl-4-yl-2(S)-hydroxy-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,5-Dimethoxy-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9(2(S)-Hydroxy-2-p-tolyl-ethyl)-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2(S)-Hydroxy-2-(3-methoxy-phenyl)-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(4-Chloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(2,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
3-Bromo-8-methyl-9-(2-oxo-2-phenyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8,8-Dimethyl-9-(2-oxo-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3,4-Dichloro-phenyl)-2(S)-hydroxy-ethyl]-8,8-dimethyl-2-(pyrimidin-4-yl)-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one
9-[2-(3-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
4-[2-(2,2-Dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydro-2H,6H-pyrimido[1,2-a]pyrimidin-1-yl)-1(S)-hydroxy-ethyl]-benzonitrile;
9-[2-(4-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(4-Methoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
8,8-Dimethyl 9-(2-naphtalen-2-yl-2-oxo-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3,4-Dichloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(2,5-Dimethoxy-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-(2-Biphenyl-4-yl-2-oxo-ethyl)-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1 ,2-a]pyrimidin-4-one;
9-[2-(3-Bromo-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(3-Fluoro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyriniidin-4-one;
8-Ethyl-9-(2-hydroxy-2-p-tolyl-ethyl)-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
9-[2-(4-Chloro-phenyl)-2-oxo-ethyl]-8,8-dimethyl-2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one; and
9-[2-(4-Chloro-phenyl)-2-hydroxy-ethyl]8-ethyl -2-pyrimidin-4-yl-6,7,8,9-tetrahydro-pyrimido[1,2-a]pyrimidin-4-one;
or a salt thereof.
6. A method for preventive and/or therapeutic treatment of non-insulin dependent diabetes which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 1 .
7. A method for preventive and/or therapeutic treatment of non-insulin dependent diabetes which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 2 .
8. A method for preventive and/or therapeutic treatment of non-insulin dependent diabetes which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 3 .
9. A method for preventive and/or therapeutic treatment of non-insulin dependent diabetes which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 4 .
10. A method for preventive and/or therapeutic treatment of non-insulin dependent diabetes which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 5 .
11. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.
12. A pharmaceutical composition comprising a compound of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising a compound of formula (I) according to claim 3 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising a compound of formula (I) according to claim 4 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.
15. A pharmaceutical composition comprising a compound of formula (I) according to claim 5 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.