2. Academic Validation
  3. Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567

Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567

  • ACS Chem Neurosci. 2010 Jan 20;1(1):19-24. doi: 10.1021/cn9000186.
Scott D Kuduk 1,  Christina N Di Marco,  Vera Bodmer-Narkevitch,  Sean P Cook,  Matthew J Cato,  Aneta Jovanovska,  Mark O Urban,  Michael Leitl,  Nova Sain,  Annie Liang,  Robert H Spencer,  Stefanie A Kane,  George D Hartman,  Mark T Bilodeau
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, P.O. Box 4, West Point, Pennsylvania 19486, USA. [email protected]
PMID: 22778804 DOI: 10.1021/cn9000186
Abstract

The synthesis, structure-activity relationship (SAR), and pharmacological evaluation of analogs of the acid-sensing ion channel (ASIC) inhibitor A-317567 are reported. It was found that the compound with an acetylenic linkage was the most potent ASIC-3 channel blocker. This compound reversed mechanical hypersensitivity in the rat iodoacetate model of osteoarthritis pain, although sedation was noted. Sedation was also observed in ASIC-3 knockout mice, questioning whether sedation and antinociception are mediated via a non-ASIC-3 specific mechanism.

Keywords

ASIC-3; Pain; acid-sensing; degenerin; ion channel.

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