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.
Stephen W Wright  1 ,  Virginia L Rath ,  Paul E Genereux ,  David L Hageman ,  Carolyn B Levy ,  Lester D McClure ,  Scott C McCoid ,  R Kirk McPherson ,  Teresa M Schelhorn ,  Donald E Wilder ,  William J Zavadoski ,  E Michael Gibbs ,  Judith L Treadway
Affiliations
  • 1. Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. [email protected]
PMID: 15603973 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.