2. Academic Validation
  3. Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain

Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain

  • Bioorg Med Chem. 2008 Jun 15;16(12):6379-86. doi: 10.1016/j.bmc.2008.05.003.
Irene Drizin 1,  Robert J Gregg,  Marc J C Scanio,  Lei Shi,  Michael F Gross,  Robert N Atkinson,  James B Thomas,  Matthew S Johnson,  William A Carroll,  Brian E Marron,  Mark L Chapman,  Dong Liu,  Michael J Krambis,  Char-Chang Shieh,  XuFeng Zhang,  Gricelda Hernandez,  Donna M Gauvin,  Joseph P Mikusa,  Chang Z Zhu,  Shailen Joshi,  Prisca Honore,  Kennan C Marsh,  Rosemarie Roeloffs,  Stephen Werness,  Douglas S Krafte,  Michael F Jarvis,  Connie R Faltynek,  Michael E Kort
Affiliations

Affiliation

  • 1 Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. [email protected]
PMID: 18501613 DOI: 10.1016/j.bmc.2008.05.003
Abstract

The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated Sodium Channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant Sodium Channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a rodent model of neuropathic pain, together with improved CNS and cardiovascular safety profiles compared to the clinically used Sodium Channel blockers mexiletine and lamotrigine.

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