2. Academic Validation
  3. Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives

Subtype-selective Na(v)1.8 sodium channel blockers: identification of potent, orally active nicotinamide derivatives

  • Bioorg Med Chem Lett. 2010 Nov 15;20(22):6812-5. doi: 10.1016/j.bmcl.2010.08.121.
Michael E Kort 1,  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,  Prisca Honore,  Rosemarie Roeloffs,  Stephen Werness,  Brett Antonio,  Kennan C Marsh,  Connie R Faltynek,  Douglas S Krafte,  Michael F Jarvis,  Brian E Marron
Affiliations

Affiliation

  • 1 Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. [email protected]
PMID: 20855211 DOI: 10.1016/j.bmcl.2010.08.121
Abstract

A series of aryl-substituted nicotinamide derivatives with selective inhibitory activity against the Na(v)1.8 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.

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