Neurological Diseases Research, Global Pharmaceutical R&D, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Bioorg Med Chem Lett. 2012 Apr 1;22(7):2604-8. doi: 10.1016/j.bmcl.2012.01.121. Epub 2012 Feb 4.
SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.
SAR 研究表明，一系列噻吩酰胺衍生物具有 CB2 受体激动剂活性。通过放射性配体结合测定、多功能测定、ADME 和药代动力学研究对化合物的活性进行了表征。具有 CB2 对 CB1 选择性的代表性化合物在神经病理性、炎性和术后疼痛的行为模型中有效产生镇痛作用。使用 CB2 拮抗剂的对照实验证明，在疼痛模型中观察到的疗效来自 CB2 激动作用。
