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
复制标题
DOI：
10.1021/jm061195
复制
发表时间：
2007-05-31
影响因子：
7.3
通讯作者：
Green, Richard
中科院分区：
文献类型：
--
作者：
Giblin, Gerard M. P.;O'Shaughnessy, Celestine T.;Green, Richard
选择性CB2受体激动剂是治疗炎症性和神经性疼痛的潜在治疗药物。聚焦筛选确定了一种嘧啶酯作为CB2受体的部分激动剂，具有微摩尔效力。随后的先导优化确定35，GW842166X为该系列的最佳化合物。35在炎症性疼痛大鼠FCA模型中的口服ED50为0.1 mg/kg，并被选为该适应症的临床候选药物。
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.