Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists

Bioorg Med Chem Lett. 2006 Jul 15;16(14):3674-8. doi: 10.1016/j.bmcl.2006.04.062. Epub 2006 May 11.

Abstract

Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Obesity Agents / chemical synthesis*
  • Anti-Obesity Agents / pharmacology*
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology*
  • Body Weight / drug effects*
  • Disease Models, Animal
  • Drug Design
  • Rats
  • Receptors, Pituitary Hormone / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Anti-Obesity Agents
  • Benzimidazoles
  • Receptors, Pituitary Hormone
  • melanin-concentrating hormone receptor