2-Alkyl/alkenyl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists |
| |
| Affiliation: | 1. Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei Province, China;2. Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, Hubei Province, China |
| |
| Abstract: | A series of 2-alkyl/alkenyl pyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Multiple compounds showed excellent and stereospecific TRPV1 antagonism with better potency than previous lead 2. Among them, compound 15f demonstrated a strong analgesic profile in a rat neuropathic pain model and blocked capsaicin-induced hypothermia in a dose-dependent manner. Docking analysis of (S)-15f with our hTRPV1 homology model provided insight into its specific binding mode. |
| |
| Keywords: | Vanilloid receptor 1 TRPV1 antagonist Capsaicin Resiniferatoxin Molecular modeling |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
