Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics

J Med Chem. 2005 Apr 7;48(7):2274-7. doi: 10.1021/jm049035q.

Abstract

Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 antagonists that exhibit in vivo efficacy in rodent obesity models.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / chemistry
  • Anti-Obesity Agents / pharmacology
  • Biological Availability
  • Brain / metabolism
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / pharmacology
  • Cycloheptanes / chemical synthesis
  • Cycloheptanes / chemistry
  • Cycloheptanes / pharmacology
  • Cyclohexanes / chemical synthesis
  • Cyclohexanes / chemistry
  • Cyclohexanes / pharmacology
  • Eating / drug effects
  • Mice
  • Obesity / drug therapy
  • Rats
  • Receptors, Pituitary Hormone / antagonists & inhibitors*
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis*
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Anti-Obesity Agents
  • Bridged Bicyclo Compounds
  • Cycloheptanes
  • Cyclohexanes
  • MCHR1 protein, rat
  • Mchr1 protein, mouse
  • Receptors, Pituitary Hormone
  • Receptors, Somatostatin
  • melanin-concentrating hormone receptor
  • Urea