4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6773-6. doi: 10.1016/j.bmcl.2013.09.096. Epub 2013 Oct 9.

Abstract

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.

Keywords: Desaturation index; Obesity; SCD1 inhibitors; Stearoyl-CoA desaturase.

MeSH terms

  • Administration, Oral
  • Animals
  • Body Weight / drug effects
  • Diet
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy
  • Piperidines / chemistry*
  • Piperidines / metabolism
  • Piperidines / pharmacology*
  • Protein Binding
  • Rats
  • Stearoyl-CoA Desaturase / antagonists & inhibitors*
  • Stearoyl-CoA Desaturase / metabolism
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / metabolism
  • Urea / pharmacology

Substances

  • Enzyme Inhibitors
  • Piperidines
  • piperidine
  • Urea
  • Stearoyl-CoA Desaturase