Zhuibai Qiu,Qiong Xie,Hongzhuan Chen,Hao Wang,Zheng Xia,Meiyan Lu,Xinghai Wang
申请号：
US12309580
公开号：
US08232270B2
申请日:
2007.07.24
申请国别(地区):
US
年份:
2012
代理人:
摘要：
The present invention belongs to pharmaceutical field. It relates to a novel family of bivalent (−)-meptazinol compounds and/or their salts, as well as the preparation and utilization of the compounds in the treatment of neurodegenerative disorders and dementias such as Alzheimers Disease (AD). In the present invention, bivalent (−)-meptazinol compounds were synthesized, from the starting material (−)-meptazinol, successively by N-demethylation forming (−)-nor-meptazinol and then by acylation with α,ω-alkanediacyl dihalides or alkylation with α,ω-dihaloalkanes. Results from in vitro cholinesterase inhibiting test and AChE-induced Aβ aggregation test demonstrated that the bivalent (−)-meptazinol compounds and/or their salts were novel bivalent inhibitors of both AChE and Aβ aggregation. The most potent compound inhibited both AChE and BChE at nM level, which was 10000 and 1500 times more potent than (−)-MEP hydrochloride, respectively. It inhibited AChE-induced Aβ aggregation by a factor of 2 compared with propidium.
