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。