Structure-activity relationship studies on N′-aryl carbohydrazide P2X7 antagonists

Derek W. Nelson, Kathy Sarris, Douglas M. Kalvin, Marian T. Namovic, George Grayson, Diana L. Donnelly-Roberts, Richard Harris, Prisca Honore, Michael F. Jarvis, Connie R. Faltynek, William A. Carroll

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

N′-Aryl acyl hydrazides were identified as P2X7 receptor antagonists. Structure-activity relationship (SAR) studies evaluated functional activity by monitoring calcium flux inhibition in cell lines expressing recombinant human and rat P2X7 receptors. Selected analogs were assayed in vitro for their capacity to inhibit release of cytokine IL-1β. Compounds with potent antagonist function were evaluated in vivo using the zymosan-induced peritonitis model. A representative compound effectively attenuated mechanical allodynia in a rat model of neuropathic pain.

Original languageEnglish (US)
Pages (from-to)3030-3034
Number of pages5
JournalJournal of Medicinal Chemistry
Volume51
Issue number10
DOIs
StatePublished - May 22 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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