Patent EA-004933-B1 (EA)
Title: 1-[ALKYL], 1-[(HETEROARYL)ALKYL] AND 1-[(ARYL)ALKYL]-7-PYPIDINYL-IMIDAZO[1,2-alpha]PYRIMIDIN-5(1H)-ONE DERIVATIVES
Inventor: LOCHEAD ALISTAIR
IPC: A61P25/28
Filed: 2001-08-31
Abstract: 1. An imidazo [1,2-alpha] pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof: wherein: X represents a bond, an ethenylene group, an ethynylene group, a methylene group optionally substituted by one or two groups selected from a C1-6 alkyl group, a hydroxy group and a C1-4 alkoxy group; a carbonyl group, an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group or a nitrogen atom being optionally substituted by a C1-6 alkyl group; R1 represents a 2,3 or 4-pyridyl group optionally substituted by a C1-4 alkyl group, C1-4 alkoxy group or a halogen atom; R2 represents a C1-6 alkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a benzyl group, a phenyl ring, a naphthyl ring, 5,6,7,8-tetrahydronaphthyl ring, a pyridyl ring, an indole ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring, the benzyl group and the rings being optionally substituted by 1 to 4 substituents selected from a C1-6 alkyl group, a phenyl ring, a halogen atom, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group, a hydroxyl group, a C1-4 alkoxy group, a nitro, a cyano, an amino, a C1-6 monoalkylamino group or a C2-10 dialkylamino group; and n represents 0 to 3. 2. An imidazo [1,2-a] pyrimidone derivative or a salt thereof, or a solvate thereof or a hydrate thereof according to claim 1, wherein R1 represents an unsubstituted 4-pyridyl group or 3-pyridyl group. 3. An imidazo [1,2-a] pyrimidone derivative or a salt thereof, or a solvate thereof or a hydrate thereof according to claim 1 or 2, a trifluoromethyl group, a 2,2,2-trifluoroethyl, a phenyl ring, a naphthyl ring, a 5,6,7,8-tetrahydronaphthyl ring or an indole ring, the rings being optionally substituted. 4. An imidazo[1,2-a]pyrimidone derivative which is selected from the group consisting of: 1): 1-[2-(phenyl) ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 2): 1-[2-(1H-indol-3-yl)ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 3): 1-[3-(phenyl) propyl]-7-pyridin-4-ylimidazo [1,2-a] pyrimidin-5(1H)-one, 4): 1-[3-(1H-indol-3-yl) propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 5): 1-[3-(4-methoxyphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 6): 1-[2-(phenoxy)ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 7): 1-[3-(2-methoxyphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 8): 1-[3-(2-chlorophenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 9): 1-[3-(2-methylphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 10): 1-[2-(phenylthio)ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 11): 1-[3-(2,5-dimethoxyphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)one, 12): 1-[3-(4-methylphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 13): 1-[3-(4-trifluoromethylphenyl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 14): 1-[4-(phenyl)butyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 15): 1-[3-(phenyl) propyl]-7-pyridin-3-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 16): 1-(2-phenyl-2-oxo-ethyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 17): (S)-1-(4,4,4-trifluoro-3-hydroxybutyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 18) :1-(4,4,4-trifluorobut-2-enyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 19): (R)-1-(4,4,4-tifluoro-3-hydroxybutyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 20): 1-(4,4,4-trifluorobut-1-enyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 21): 1-[2-(2,5-dimethoxyphenyl)ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 22): 1-[3-(2-fluorophenyl) propyl]-7-pyridin-4-ylimidazo [1,2-a] pyrimidin-5(1H)-one, 23): 1-(3-phenyl-3-oxo-propyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 24): 1-[3-(pyridin-3-yl)propyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 25): (S)-1-(4,4,4-trifluoro-butyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 26): 1-[2-(2-methoxyphenyl)ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 27): 1-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 28): 1-[2-(4-phenyl-phenyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 29): 1-[2-(3-methoxyphenyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 30): 1-[2-(2-naphthyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 31): 1-[2-(4-methylphenyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 32): 1-[2-(4-fluorophenyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 33): 1-[2-(4-chlorophenyl)-2-oxo-ethyl]-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 34): 1-(2-(4-fluorophenyl)-2-hydroxyethyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 35): 1-(2-naphthyl-2-hydroxyethyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, 36): 1-(2-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-6-yl)-2-hydroxyethyl)-7-pyridin-4-ylimidazo[1,2-a]pyrimidin-5(1H)-one, or a salt thereof, or a solvate thereof or a hydrate thereof. 5. A medicament comprising as an active ingredient a substance selected from the group consisting of an imidazo [1,2-a] pyrimidone derivative represented by formula (I) or salts thereof, or a solvate thereof or a hydrate thereof according to claim 1. 6. A GSK3beta inhibitor selected from the group of a imidazo [1,2-a] pyrimidone derivative represented by formula (I) or salts thereof, or a solvate thereof or a hydrate thereof according to claim 1. 7. Use of a compound according to claims 1 to 4 for the preparation of a medicament for preventive and/or therapeutic treatment of a disease caused by abnormal GSK3beta activity. 8. Use of a compound according to claims 1 to 4 for the preparation of a medicament for preventive and/or therapeutic treatment of a neurodegenerative disease. 9. Use of a compound according to claim 8, wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, Parkinson's disease, tauopathies, vascular dementia; acute stroke, traumatic injuries; cerebrovascular accidents, brain cord trauma, spinal cord trauma; peripheral neuropathies; retinopathies or glaucoma. 10. Use of a compound according to claims 1 to 4 for the preparation of a medicament for preventive and/or therapeutic treatment of non-insulin dependent diabetes; obesity; manic depressive illness; schizophrenia; alopecia; or cancers. 11. Use according to claim 10 wherein cancer is breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia or virus-induced tumors.