Cyclopropylamino acid amide as a pharmacophoric replacement for 2,3-diaminopyridine. Application to the design of novel bradykinin B1 receptor antagonists

J Med Chem. 2006 Feb 23;49(4):1231-4. doi: 10.1021/jm0511280.

Abstract

Antagonism of the bradykinin B1 receptor represents a potential treatment for chronic pain and inflammation. Novel antagonists were designed that display low-nanomolar affinity for the human bradykinin B1 receptor and good bioavailability in the rat.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biological Availability
  • Bradykinin B1 Receptor Antagonists*
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Drug Design
  • Humans
  • Molecular Conformation
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bradykinin B1 Receptor Antagonists
  • Cyclopropanes
  • Pyridines