Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4151-8. doi: 10.1016/j.bmcl.2009.05.119. Epub 2009 Jun 2.

Abstract

A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred C57BL
  • Models, Chemical
  • Stearoyl-CoA Desaturase / antagonists & inhibitors*
  • Stearoyl-CoA Desaturase / chemistry
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology

Substances

  • 3-(2-hydroxyethoxy)-4-methoxy-N-(5-(3-trifluoromethylbenzyl)thiazol-2-yl)benzamide
  • Benzamides
  • Enzyme Inhibitors
  • Thiazoles
  • Stearoyl-CoA Desaturase