Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain

  • ACS Med Chem Lett. 2015 Apr 29;6(6):650-4. doi: 10.1021/acsmedchemlett.5b00059.
Sharan K Bagal  1 ,  Peter J Bungay  2 ,  Stephen M Denton  3 ,  Karl R Gibson  3 ,  Melanie S Glossop  3 ,  Tanya L Hay  3 ,  Mark I Kemp  3 ,  Charlotte A L Lane  3 ,  Mark L Lewis  3 ,  Graham N Maw  3 ,  William A Million  3 ,  C Elizabeth Payne  2 ,  Cedric Poinsard  3 ,  David J Rawson  3 ,  Blanda L Stammen  3 ,  Edward B Stevens  2 ,  Lisa R Thompson  3
Affiliations
  • 1. Worldwide Medicinal Chemistry, Pfizer Neusentis , The Portway Building, Granta Park, Great Abington, Cambridge CB21 6GS, U.K.
  • 2. Neusentis U.K., Pfizer Global R&D , The Portway Building, Granta Park, Cambridge CB21 6GS, U.K.
  • 3. Worldwide Medicinal Chemistry, Pfizer Global R&D , Sandwich CT13 9NJ, U.K.
PMID: 26101568 DOI: 10.1021/acsmedchemlett.5b00059
Abstract

Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Nav1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.

Keywords
Nav1.8; SCN10A; TTX-R; Voltage-gated sodium channels; sodium channel drugs.
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