A new class of bradykinin 1 receptor antagonists containing the piperidine acetic acid tetralin core

Bioorg Med Chem Lett. 2006 Apr 15;16(8):2071-5. doi: 10.1016/j.bmcl.2006.01.069. Epub 2006 Feb 7.

Abstract

The bradykinin 1 (B1) receptor is upregulated during times of inflammation and is important for maintaining inflamed and chronic pain states. Blocking this receptor has been shown to reverse and/or ameliorate pain and inflammation in animal models. In this report, we describe a new class of B1 receptor antagonists that contain the piperidine acetic acid tetralin core. A structure-activity relationship for these analogs is described in this paper. The most potent compounds from this class have IC50s<20 nM in a B1 receptor functional assay. One of these compounds, 13g, shows modest oral bioavailability in rats.

MeSH terms

  • Acetic Acid / chemistry
  • Administration, Oral
  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biological Availability
  • Bradykinin B1 Receptor Antagonists*
  • Inhibitory Concentration 50
  • Piperidines / chemistry
  • Rats
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemistry*

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Bradykinin B1 Receptor Antagonists
  • Piperidines
  • Tetrahydronaphthalenes
  • piperidine
  • tetralin
  • Acetic Acid