Discovery and SAR of biaryl piperidine MCH1 receptor antagonists through solid-phase encoded combinatorial synthesis

Bioorg Med Chem Lett. 2005 Aug 15;15(16):3696-700. doi: 10.1016/j.bmcl.2005.05.085.

Abstract

An encoded combinatorial library based on aryl and biaryl piperidine scaffolds was designed and synthesized. Screening of this library resulted in the discovery of high-nanomolar biaryl piperidine-based MCH1 receptor antagonists. Follow-up optimization using a parallel synthesis provided potent, single digit nanomolar antagonists.

MeSH terms

  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Molecular Structure
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • MCHR1 protein, human
  • Piperidines
  • Receptors, Somatostatin