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 Infla

详细信息    查看全文

• 作者：Gerard M. P. Giblin ; 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.
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：May 31, 2007
• 年：2007
• 卷：50
• 期：11
• 页码：2597 - 2600
• 全文大小：52K
• 年卷期：v.50,no.11(May 31, 2007)
• ISSN：1520-4804

文摘

Selective CB2 receptor agonists are promising potentialtherapeutic agents for the treatment of inflammatory and neuropathicpain. A focused screen identified a pyrimidine ester as a partial agonistat the CB2 receptor with micromolar potency. Subsequent leadoptimization identified 35, GW842166X, as the optimal compound inthe series. 35 has an oral ED₅₀ of 0.1 mg/kg in the rat FCA model ofinflammatory pain and was selected as a clinical candidate for thisindication.