Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase

J Nat Prod. 2009 Aug;72(8):1414-8. doi: 10.1021/np9002367.

Abstract

The 3-deoxy-2-keto derivatives 5 and 7 of oleanolic acid (1) and ursolic acid (2), respectively, served as precursors to the synthesis of 35 3-deoxy derivatives of pentacyclic triterpenes. The synthesized compounds were biologically assayed for their inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Among this series of compounds, 2alpha-hydroxyurs-12-en-28-oic acid (18) (IC(50) = 1.2 microM) exhibited the most potent activity. Preliminary structure-activity relationship analysis for the 3-deoxy triterpene derivatives as GP inhibitors is also discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Molecular Structure
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Pentacyclic Triterpenes / chemical synthesis*
  • Pentacyclic Triterpenes / chemistry
  • Pentacyclic Triterpenes / pharmacology*
  • Rabbits
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology
  • Ursolic Acid

Substances

  • Pentacyclic Triterpenes
  • Triterpenes
  • Oleanolic Acid
  • corosolic acid
  • Glycogen Phosphorylase