Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through solid-phase parallel synthesis

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3691-5. doi: 10.1016/j.bmcl.2005.05.039.

Abstract

-4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor (MCH1R) antagonists via screening using a scintillation proximity assay based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead optimization efforts using solid-phase parallel synthesis resulted in the defined structure-activity relationships and the identification of 4-amino-2-biarylbutylureas, such as 11g, as potent single digit nanomolar MCH1R antagonists.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Structure
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Urea / analogs & derivatives
  • Urea / chemical synthesis*
  • Urea / pharmacology*

Substances

  • MCHR1 protein, human
  • Receptors, Somatostatin
  • Urea