Amino acid anthranilamide derivatives as a new class of glycogen phosphorylase inhibitors

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4068-71. doi: 10.1016/j.bmcl.2008.05.102. Epub 2008 Jun 12.

Abstract

A series of amino acid anthranilamide derivatives identified from a high-throughput screening campaign as novel, potent, and glucose-sensitive inhibitors of human liver glycogen phosphorylase a are described. A solid-phase synthesis using Wang resin was also developed which provided efficient access to a variety of analogues, and resulted in the identification of key structure-activity relationships, and the discovery of a potent exemplar (IC(50)=80 nM). The SAR scope, synthetic strategy, and in vitro results for this series are presented herein.

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Glycogen Phosphorylase, Liver Form / antagonists & inhibitors*
  • Glycogen Phosphorylase, Liver Form / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Liver / enzymology
  • Microsomes, Liver / enzymology
  • Models, Chemical
  • Rats
  • Structure-Activity Relationship
  • Urea / chemistry
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology

Substances

  • Amino Acids
  • ortho-Aminobenzoates
  • Urea
  • Glycogen Phosphorylase, Liver Form
  • anthranilamide