Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligands

Bioorg Med Chem Lett. 2006 Feb 15;16(4):934-7. doi: 10.1016/j.bmcl.2005.10.097. Epub 2005 Nov 16.

Abstract

A novel series of 2-anilino-3-phenylsulfonyl-6-methylpyridines was synthesized and evaluated as corticotropin-releasing factor receptor ligands. Structure-activity relationship studies focused primarily on optimization of the 3-phenylsulfonyl group. Compounds within this series were identified which showed potent binding affinity for the CRF1 receptor. Selected compounds were examined in a rat pharmacokinetic study and were found to have oral bioavailabilities ranging from 16 to 35%.

MeSH terms

  • Administration, Oral
  • Animals
  • Crystallography, X-Ray
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Pyridines / administration & dosage
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Rats
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Ligands
  • Pyridines
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1