Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists |
| |
Authors: | Brown Brian S Keddy Ryan Zheng Guo Zhu Schmidt Robert G Koenig John R McDonald Heath A Bianchi Bruce R Honore Prisca Jarvis Michael F Surowy Carol S Polakowski James S Marsh Kennan C Faltynek Connie R Lee Chih-Hung |
| |
Institution: | Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Dept R4PM, AP10-207, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. brian.s.brown@abbott.com |
| |
Abstract: | A series of 1,2,3,6-tetrahydropyridyl-4-carboxamides, exemplified by 6, have been synthesized and evaluated for in vitro TRPV1 antagonist activity, and in vivo analgesic activity in animal pain models. The tetrahydropyridine 6 is a novel TRPV1 receptor antagonist that potently inhibits receptor-mediated Ca2+ influx in vitro induced by several agonists, including capsaicin, N-arachidonoyldopamine (NADA), and low pH. This compound penetrates the CNS and shows potent anti-nociceptive effects in a broad range of animal pain models upon oral dosing due in part to its ability to antagonize both central and peripheral TRPV1 receptors. The SAR leading to the discovery of 6 is presented in this report. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|