Bradykinin B1 antagonists: biphenyl SAR studies in the cyclopropanecarboxamide series

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3608-12. doi: 10.1016/j.bmcl.2007.04.040. Epub 2007 Apr 24.

Abstract

SAR study of the biphenyl region of cyclopropanecarboxamide derived bradykinin B(1) antagonists was examined. Incorporation of a pyridine in place of the proximal phenyl ring and chlorination of the distal phenyl ring proved to be well tolerated and provided compounds with improved pharmacokinetic profiles, CNS penetration, and enhanced receptor occupancy.

MeSH terms

  • Amides / chemistry*
  • Animals
  • Bradykinin B1 Receptor Antagonists*
  • Central Nervous System / drug effects
  • Chemistry, Pharmaceutical / methods
  • Chlorine / chemistry
  • Cyclopropanes / chemistry
  • Drug Design
  • Humans
  • Models, Chemical
  • Phenol / chemistry
  • Pyridines / chemistry
  • Rats
  • Structure-Activity Relationship

Substances

  • Amides
  • Bradykinin B1 Receptor Antagonists
  • Cyclopropanes
  • Pyridines
  • Phenol
  • Chlorine
  • cyclopropane
  • pyridine