Substituted 8'-pyridinyl-dihydrospiro-(cycloalkyl)-pyrimido(1,2-a) pyrimidin-6-one and 8'-pyrimidinyl-dihydrospiro-(cycloalkyl)-pyrimido(1,2-a)pyrimidin-6-one derivatives and their use against neurodegenerative diseases
申请人:SANOFI-SYNTHELABO
公开号:EP1454909A1
公开(公告)日:2004-09-08
The invention relates to a dihydrospiro-[cycloalkyl]-pyrimidone derivative represented by formula (I) or a salt thereof:
wherein:
X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom;
Y represents a bond, a carbonyl group, a methylene group optionally substituted;
R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted;
R2 represents a benzene ring or a naphthalene ring; the rings being optionally substituted;
R3 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom;
m represents 1 to 4
n represent 0 to 3
p represents 0 to 2
q represents 0 to 2, p+ q being inferior to 4.
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, such as Alzheimer disease.
本发明涉及式 (I) 所代表的二氢螺-[环烷基]-嘧啶酮衍生物或其盐:
其中
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 代表键、羰基、任选取代的亚甲基;
R1 代表 2、3 或 4-吡啶环或 2、4 或 5-嘧啶环,环可任选被取代;
R2 代表苯环或萘环;这些环可任选被取代;
R3 代表氢原子、C1-6 烷基或卤素原子;
m 代表 1 至 4
n 代表 0 至 3
p 代表 0 至 2
q 代表 0 至 2,p+ q 不如 4。
本发明还涉及一种包含上述衍生物或其盐作为活性成分的药物,该药物用于预防和/或治疗由 GSK3β 活性异常引起的神经退行性疾病,如阿尔茨海默病。