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.

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