5-Chloroindoloyl glycine amide inhibitors of glycogen phosphorylase: synthesis, in vitro, in vivo, and X-ray crystallographic characterization

Bioorg Med Chem Lett. 2005 Jan 17;15(2):459-65. doi: 10.1016/j.bmcl.2004.10.048.

Abstract

The synthesis, in vitro, and in vivo biological characterization of a series of achiral 5-chloroindoloyl glycine amide inhibitors of human liver glycogen phosphorylase A are described. Improved potency over previously reported compounds in cellular and in vivo assays was observed. The allosteric binding site of these compounds was shown by X-ray crystallography to be the same as that reported previously for 5-chloroindoloyl norstatine amides.

MeSH terms

  • Allosteric Site
  • Amides / chemical synthesis*
  • Amides / pharmacology
  • Aminocaproates / chemistry
  • Aminocaproates / pharmacology
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Glycine / chemistry
  • Glycine / pharmacology
  • Glycogen Phosphorylase / antagonists & inhibitors*
  • Glycogen Phosphorylase / metabolism
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Liver / enzymology
  • Liver / metabolism

Substances

  • 5-chloroindoloyl glycine amide
  • Amides
  • Aminocaproates
  • Enzyme Inhibitors
  • Indoles
  • 3-amino-2-hydroxy-5-methylhexanoic acid
  • Glycogen Phosphorylase
  • Glycine