Development of New Benzenesulfonamides As Potent and Selective Nav1.7 Inhibitors for the Treatment of Pain.
J Med Chem
; 60(6): 2513-2525, 2017 03 23.
Article
em En
| MEDLINE
| ID: mdl-28234467
ABSTRACT
By taking advantage of certain features in piperidine 4, we developed a novel series of cyclohexylamine- and piperidine-based benzenesulfonamides as potent and selective Nav1.7 inhibitors. However, compound 24, one of the early analogs, failed to reduce phase 2 flinching in the mouse formalin test even at a dose of 100 mpk PO due to insufficient dorsal root ganglion (DRG) exposure attributed to poor membrane permeability. Two analogs with improved membrane permeability showed much increased DRG concentrations at doses of 30 mpk PO, but, confoundingly, only one of these was effective in the formalin test. More data are needed to understand the disconnect between efficacy and exposure relationships.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Sulfonamidas
/
Bloqueadores do Canal de Sódio Disparado por Voltagem
/
Analgésicos
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article