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
申请人:——
公开号:US20040266793A1
公开(公告)日:2004-12-30
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 GSK3&bgr;3 or GSK3&bgr;3 and cdk5/p25, such as Alzheimer disease.
1
本发明涉及一种由式(I)表示的
嘧啶酮衍
生物或其盐,其中:X代表两个
氢原子,
硫原子,
氧原子或C1-2烷基和
氢原子;y代表键,
乙烯基,
乙炔基,
氧原子,
硫原子,磺酰基,亚
磺酸基,羰基,
氮原子(可选)或取代的亚
甲基基团;R1表示可选取代的
嘧啶基团;R2可以代表C1-6烷基,可选地被C6,10芳
氧基或C6,10芳基
氨基基团取代;C3-6
环烷基,C1-4烷基
硫基,C1-4烷
氧基,C1-2
全氟烷基,C1-3卤代烷基,
苯硫基,
苄基,
苯环,
茚环,5,6,7,8-四
氢萘环,
萘环,
吡啶环,
吡咯环,
噻吩环,
呋喃环或
咪唑环;R3和R4各自独立地表示
氢原子,C1-6烷基,羟基,C1-4烷
氧基或卤素原子;R5表示
氢原子,C1-6烷基或卤素原子。本发明还涉及一种药物,其中包括所述衍
生物或其盐作为活性成分,用于预防和/或治疗由GSK3β3或GSK3β3和cdk5/p25的异常活性引起的神经退行性疾病,例如阿尔茨海默病。