2. Academic Validation
  3. Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain

Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain

  • J Med Chem. 2007 May 31;50(11):2597-600. doi: 10.1021/jm061195+.
Gerard M P Giblin 1,  Celestine T O'Shaughnessy,  Alan Naylor,  William L Mitchell,  Andrew J Eatherton,  Brian P Slingsby,  D Anthony Rawlings,  Paul Goldsmith,  Andrew J Brown,  Carl P Haslam,  Nick M Clayton,  Alex W Wilson,  Iain P Chessell,  Andrew R Wittington,  Richard Green
Affiliations

Affiliation

  • 1 Neurology and GI Centre of Excellence for Drug Discovery, Molecular Discovery Research, GlaxoSmithKline, New Frontiers Park, Harlow, Essex, CM19 5AW, UK. [email protected]
PMID: 17477516 DOI: 10.1021/jm061195+
Abstract

Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.

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