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Updated: Jul 2, 2026

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
Published on: December 31, 2013
Tetrahydropyridine-4-carboxamides as novel, potent transient receptor potential vanilloid 1 (TRPV1) antagonists
Brian S Brown1, Ryan Keddy, Guo Zhu Zheng
1Neuroscience 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.
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