Abstract: 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 Alzheimer'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 ?,?-alkanediacyl dihalides or alkylation with ?,?-dihaloalkanes. Results from in vitro cholinesterase inhibiting test and AChE-induced A? aggregation test demonstrated that the bivalent (?)-meptazinol compounds and/or their salts were novel bivalent inhibitors of both AChE and A? 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.

Abstract: 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 Alzheimer'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 ?,?-alkanediacyl dihalides or alkylation with ?,?-dihaloalkanes. Results from in vitro cholinesterase inhibiting test and AChE-induced A? aggregation test demonstrated that the bivalent (?)-meptazinol compounds and/or their salts were novel bivalent inhibitors of both ACHE and A? 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.