Synthesis of conjugates of ipidacrine with oxa/azaheterocycles and their potential as agents for the treatment of Alzheimer’s disease

Abstract

Ipidacrine conjugates were synthesized by alkylation of 4-hydroxycoumarin, dihydrofuro[3,4-c]pyridine, bipyridine, and azolo[1,5-a]pyrimidines with 2-chloro-N-(hexahydrocyclopenta[b]quinolin-9-yl)acetamide. Their isomeric structure was determined by NMR spectroscopy. Heterocycles containing ambident N,O-nucleophilic centers underwent alkylation at the oxygen atom, while in the presence of alternative carboxy and hydroxy functions, the alkylation occurred with the formation of an ester derivative. The study of the esterase profile, inhibitory effect on β-amyloid self-aggregation, as well as antioxidant activity of the conjugates, showed that coumarin derivatives are promising for the development of butyrylcholinesterase inhibitors, whereas conjugates of azolo[1,5-a]-pyrimidines are promising in the search for β-amyloid self-aggregation inhibitors.