2-Aminopyridines as Potent and Selective Nav1.8 Inhibitors Exhibiting Efficacy in a Nonhuman Primate Pain Model.
ACS Med Chem Lett
; 15(6): 917-923, 2024 Jun 13.
Article
de En
| MEDLINE
| ID: mdl-38894930
ABSTRACT
Herein we describe the discovery of a 2-aminopyridine scaffold as a potent and isoform selective inhibitor of the Nav1.8 sodium channel. Parallel library synthesis, guided by in silico predictions, rapidly transformed initial hits into a novel 2-aminopyridine lead class possessing good ADME and pharmacokinetic profiles that were able to display activity in a clinically translatable nonhuman primate capsaicin-sensitized thermode pharmacodynamic assay. Progress toward the lead identification, optimization, and in vivo efficacy of these compounds will be discussed.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
ACS Med Chem Lett
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique