Ognyanov, Vassil I. Balan, Chenera Bannon, Anthony W. Bo, Yunxin Dominguez, Celia Fotsch, Christopher Gore, Vijay K. Klionsky, Lana Ma, Vu V. Qian, Yi-Xin Tamir, Rami Wang, Xianghong Xi, Ning Xu, Shimin Zhu, Dawn Gavva, Narender R. J. S. Treanor, James Norman, Mark H. Design of Potent, Orally Available Antagonists of the Transient Receptor Potential Vanilloid 1. Structure−Activity Relationships of 2-Piperazin-1-yl-1<i>H</i>-benzimidazoles The vanilloid receptor-1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Herein, we describe the synthesis and the structure−activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1<i>H</i>-benzo[<i>d</i>]imidazoles as novel TRPV1 antagonists. Compound <b>46ad</b> was among the most potent analogues in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. Compound <b>46ad</b> also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant (CFA). series;antihyperalgesic effects;nonselective cation channel;TRPV 1 antagonists;VR 1;novel TRPV 1 antagonists;Transient Receptor;Compound 46 ad;neuropathic pain;CFA;animal models 2006-06-15
    https://acs.figshare.com/articles/journal_contribution/Design_of_Potent_Orally_Available_Antagonists_of_the_Transient_Receptor_Potential_Vanilloid_1_Structure_Activity_Relationships_of_2_Piperazin_1_yl_1_i_H_i_benzimidazoles/3075652
10.1021/jm060065y.s001