Discovery of novel hydroxy-thiazoles as HIF-alpha prolyl hydroxylase inhibitors: SAR, synthesis, and modeling evaluation

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3925-8. doi: 10.1016/j.bmcl.2008.06.031. Epub 2008 Jun 13.

Abstract

Inhibition of the PHD2 enzyme has been associated with increased red blood cell levels. From a screening hit, a series of novel hydroxyl-thiazoles were developed as potent PHD2 inhibitors.

MeSH terms

  • Chemistry, Pharmaceutical / methods
  • Diabetes Mellitus / drug therapy
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Erythrocytes / enzymology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemical synthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Inhibitory Concentration 50
  • Models, Chemical
  • Models, Molecular
  • Myocardial Infarction / drug therapy
  • Peripheral Vascular Diseases / therapy
  • Stroke / drug therapy
  • Structure-Activity Relationship
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Thiazoles