Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor

R Obata; T Sunazuka; K Otoguro; H Tomoda; Y Harigaya; S Omura

doi:10.1016/s0960-894x(00)00218-3

Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor

Bioorg Med Chem Lett. 2000 Jun 19;10(12):1315-6. doi: 10.1016/s0960-894x(00)00218-3.

Authors

R Obata¹, T Sunazuka, K Otoguro, H Tomoda, Y Harigaya, S Omura

Affiliation

¹ Research Center for Biological Function, The Kitasato Institute and Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

PMID: 10890154
DOI: 10.1016/s0960-894x(00)00218-3

Abstract

Natural product acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor pyripyropene A was synthetically converted to acetylcholinesterase (AChE) inhibitor via heterolitic cleavage of the 2-pyrone ring, followed by gamma-acylation/cyclization with several aroyl chlorides. The 4-pyridyl analogue selectively showed AChE inhibitory activity (IC50 7.9 microM) and no ACAT inhibitory activity IC50 = >1000 microM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cholinesterase Inhibitors / pharmacology*
Enzyme Inhibitors / pharmacology*
Humans
Sterol O-Acyltransferase / antagonists & inhibitors*

Substances

Cholinesterase Inhibitors
Enzyme Inhibitors
Sterol O-Acyltransferase