申请人:ASTRAZENECA AB
公开号:WO2010053438A1
公开(公告)日:2010-05-14
The present invention relates to novel compounds of formula I and therapeutically acceptable salts thereof, their pharmaceutical compositions, processes for making them and their use as therapeutic methods for treatment and/or prevention of various diseases. In particular the invention relates to compounds, which inhibit the Aβ40 and Aβ42 production, increase the Aβ37 and Aβ38 production and maintain the Notch signaling and will be used for treatment and/or prevention of Aβ-related pathologies such as Alzheimer's disease, Downs syndrome and β-amyloid angiopathy, such as but not limited to cerebral amyloid angiopathy, hereditary cerebral hemorrhage, disorders associated with cognitive impairment, such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
本发明涉及式I的新化合物及其治疗上可接受的盐,它们的药物组合物,制造它们的方法以及它们作为治疗和/或预防各种疾病的治疗方法的使用。特别是,本发明涉及抑制Aβ40和Aβ42产生,增加Aβ37和Aβ38产生并维持Notch信号传导的化合物,并将用于治疗和/或预防与Aβ相关的病理,如阿尔茨海默病、唐氏综合症和β-淀粉样蛋白血管病,例如但不限于脑淀粉样血管病、遗传性脑出血、与认知障碍相关的疾病,例如但不限于MCI(“轻度认知障碍”)、阿尔茨海默病、记忆丧失、与阿尔茨海默病相关的注意力缺陷症状、与阿尔茨海默病或包括混合血管和退行性来源的痴呆在内的疾病相关的神经退行性变、早老性痴呆、老年性痴呆和与帕金森病、进行性核上瘫或皮层基底退行性变相关的痴呆。