| Autor: |
Davina Owen, Kevin Gunn, Himanshu Naik, Francois Rugiero, Giuseppe Alvaro, Gerard M. P. Giblin, Dominique Derjean, David R Witty, Valerie Morisset, Simon Tate, David T. MacPherson, Charles Large, Christopher A Hinckley, Joanne Palmer |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| Popis: |
[Image: see text] Drugs that block voltage-gated sodium channels (Na(V)s) have utility in treating conditions including pain, epilepsy, and cardiac arrhythmias and as anesthetics (Lancet Neurol.2010941342420298965; Expert Opin. Ther. Pat.20102075577920384535). The identification of compounds with improved efficacy and safety is a key aim for the discovery of improved Na(V) blocking drugs (Comprehensive Medicinal Chemistry III; Elsevier, 2017; pp 131−175). We report the identification of a novel class of brain penetrant and voltage-gated sodium channel blockers, leading to the discovery of vixotrigine, a use-dependent sodium channel blocker with activity in in vivo models of pain. Vixotrigine has excellent physiocochemical properties for drug development, and both preclinical and clinical data support a safety profile suitable for potential use in neuropathic pain and other conditions. It has shown efficacy in a Phase II study for pain associated with trigeminal neuralgia. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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