Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 1

Masaki Ohtawa; Hiroyuki Yamazaki; Satoshi Ohte; Daisuke Matsuda; Taichi Ohshiro; Lawrence L Rudel; Satoshi Omura; Hiroshi Tomoda; Tohru Nagamitsu

doi:10.1016/j.bmcl.2012.12.099

Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 1

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1285-7. doi: 10.1016/j.bmcl.2012.12.099. Epub 2013 Jan 9.

Authors

Masaki Ohtawa¹, Hiroyuki Yamazaki, Satoshi Ohte, Daisuke Matsuda, Taichi Ohshiro, Lawrence L Rudel, Satoshi Omura, Hiroshi Tomoda, Tohru Nagamitsu

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

PMID: 23369538
DOI: 10.1016/j.bmcl.2012.12.099

Abstract

In an effort to develop potent and selective inhibitors toward ACAT2, structure-activity relationship studies were carried out using derivatives based on pyripyropene A (PPPA, 1). We have successfully developed novel PPPA derivatives with a 7-O-substituted benzoyl substituent that significantly exhibit more potent ACAT2 inhibitory activity and higher ACAT2 isozyme selectivity than 1.

Publication types

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

MeSH terms

Animals
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology*
Sesquiterpenes / chemical synthesis
Sesquiterpenes / chemistry*
Sesquiterpenes / pharmacology*
Sterol O-Acyltransferase / antagonists & inhibitors*
Sterol O-Acyltransferase 2
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Pyridines
Sesquiterpenes
pyripyropene A
Sterol O-Acyltransferase