|
|||||
|
|
Subtype-selective Nav1.8 sodium channel blockers: Identification of potent,orally active nicotinamide derivatives |
|
| Authors: | Michael E. Kort Robert N. Atkinson James B. Thomas Irene Drizin Matthew S. Johnson Matthew A. Secrest Robert J. Gregg Marc J.C. Scanio Lei Shi Ahmed H. Hakeem Mark A. Matulenko Mark L. Chapman Michael J. Krambis Dong Liu Char-Chang Shieh XuFeng Zhang Gricelda Simler Joseph P. Mikusa Chengmin Zhong Shailen Joshi Brian E. Marron |
| Affiliation: | 1. Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA;2. Icagen, Inc., 4222 Emperor Blvd., Durham, NC 27703, USA |
| Abstract: | A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Nav1.8 sodium channel is reported. Replacement of the furan nucleus and homologation of the anilide linker in subtype-selective blocker A-803467 (1) provided potent, selective derivatives with improved aqueous solubility and oral bioavailability. Representative compounds from this series displayed efficacy in rat models of inflammatory and neuropathic pain. |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |