Synthesis and structure-activity relationships of biarylcarboxamide bis-aminopyrrolidine urea derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1)

Bioorg Med Chem Lett. 2005 Jul 15;15(14):3439-45. doi: 10.1016/j.bmcl.2005.05.015.

Abstract

A novel series of bis-aminopyrrolidine ureas containing either a 4-biphenylcarboxmide or 5-phenyl-2-thiophenecarboxamide group have been identified as potent and functional antagonists of the melanin-concentrating hormone receptor-1. Syntheses and SAR are described, which led to the discovery of compounds with high binding affinity (Ki = 1 nM) for the receptor. Preliminary in vitro metabolic stability data are also reported for key compounds.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides* / chemical synthesis
  • Amides* / pharmacology
  • Animals
  • Drug Design
  • Molecular Conformation
  • Molecular Weight
  • Pyrrolidines* / chemical synthesis
  • Pyrrolidines* / pharmacology
  • Rats
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Urea* / analogs & derivatives
  • Urea* / chemical synthesis
  • Urea* / pharmacology

Substances

  • Amides
  • MCHR1 protein, rat
  • Pyrrolidines
  • Receptors, Somatostatin
  • Urea