Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives
申请人:Lochead Alistair
公开号:US20050222172A1
公开(公告)日:2005-10-06
The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (1) 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 or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring optionally substituted; R2 represents a heterocyclic bicyclic rings, having 1-4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5-9 carbon atoms, of formula (II) R3 represents a hydrogen atom, a C
1-6
alkyl group, a hydroxy group, a C
1-4
alkoxy group or a halogen atom; R4 represents a hydrogen atom, a C
1-6
alkyl group, a C
1-4
alkoxy 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 GSK3β or GSK3β and cdk5/p25, such as Alzheimer disease.
本发明涉及一种由式(I)表示的嘧啶酮衍生物或其盐,其中:(1)X代表两个氢原子、一个硫原子、一个氧原子或一个C1-2烷基和一个氢原子;Y代表一种键合、一个乙烯基、一个乙炔基或一个甲基烷基,可选地取代;R1代表一个2、3或4-吡啶环或一个2、4或5-嘧啶环,可选地取代;R2代表一种杂环双环环,具有1-4个从氧原子、硫原子和氮原子中选择的杂原子,并具有5-9个碳原子,其式为(II)R3代表氢原子、C1-6烷基、羟基、C1-4烷氧基或卤素原子;R4代表氢原子、C1-6烷基、C1-4烷氧基或卤素原子。本发明还涉及一种药物,其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GSK3β或GSK3β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。