Divalent (-)-meptazinol compound and / or salt thereof, production method and use

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 Alzhermer's 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 ±,É-alkanediacyl dihalides or alkylation with ±,É-dihaloalkanes. Results from in vitro cholinesterase inhibiting test and AChE-induced A² aggregation test demonstrated that the bivalent (-)-meptazinol compounds and/or their salts were novel bivalent inhibitors of both AChE and A² 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 A² aggregation by a factor of 2 compared with propidium.