Synthesis and in vitro activity of N-benzyl-1-(2,3-dichlorophenyl)-1H- tetrazol-5-amine P2X 7 antagonists

Arturo Perez-Medrano*, Diana L. Donnelly-Roberts, Alan S. Florjancic, Derek W. Nelson, Tongmei Li, Marian T. Namovic, Sridhar Peddi, Connie R. Faltynek, Michael F. Jarvis, William A. Carroll

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Synthesis and biological evaluation of a novel class of substituted N-benzyl-1-(2,3-dichlorophenyl)-1H-tetrazol-5-amine derivatives resulted in the identification of potent P2X 7 antagonists. These compounds were assayed for activity at both the human and rat P2X 7 receptors. On the benzyl moiety, a variety of functional groups were tolerated, including both electron-withdrawing and electron-donating substituents. Ortho-substitution on the benzyl group provided the greatest potency. The ortho-substituted analogs showed approximately 2.5-fold greater potency at human compared to rat P2X 7 receptors. Compounds 12 and 38 displayed hP2X 7 pIC 50s >7.8 with less than 2-fold difference in potency at the rP2X 7.

Original languageEnglish (US)
Pages (from-to)3297-3300
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • Antagonists
  • P2X
  • Pain
  • SAR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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