Design and synthesis of simple, yet potent and selective non-ring-A pyripyropene A-based inhibitors of acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2)

Org Biomol Chem. 2016 Jan 14;14(2):747-751. doi: 10.1039/c5ob02019k.

Abstract

A series of pyripyropene A-based compounds were designed and synthesized by opening the upper section of the A-ring, which significantly simplifies the structure and synthesis from commercially available starting materials. Representative compound (-)-3 exhibited potent activity against ACAT2 and greater selectivity for ACAT2 than for ACAT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Sterol O-Acyltransferase / antagonists & inhibitors*
  • Sterol O-Acyltransferase / metabolism
  • Sterol O-Acyltransferase 2
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Pyridines
  • Sesquiterpenes
  • pyripyropene A
  • Sterol O-Acyltransferase