Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB2 receptor agonists for pain management

Abstract 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.