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
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2024
Type:
Article
Affiliation country:
United States