Synthesis and anti-acetylcholinesterase activity of 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2-yl)methyl]piperidine hydrochloride (E2020) and related compounds

Bioorganic & Medicinal Chemistry Letters
1992.0

Abstract

In the previous paper, 1 -benzyl-4-{2-[N-(4'-benzylsulfonyl)benzoyl-N-methylamino]-e~hyl}pipe~dine hydrochloride (1) was shown to be a potent acetylcholinesterase (AChE) inhibitor. The structureactivity relationship (SAR) of the rigid compounds, 1-benzyl-4-[2-(N-phthalimid-l-yl)ethyl]piperidine hydrochlorides (2) has been reported. These results show that the amide and N-benzylpiperidine moieties are required for biological activity. Our findings also indicate that a variety of atoms (X=N, C) is tolerated at the amide nitrogen position. In order to explore further these structural requirements, indanone derivatives (3, X=C) were synthesized (Fig. 1). The results of our study on the synthesis, SAR and pharmacology of these are described herein.

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