Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.
Bioorg Med Chem Lett
; 26(4): 1156-60, 2016 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-26804230
ABSTRACT
Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Proteínas Proto-Oncogênicas B-raf
/
Inibidores de Proteínas Quinases
/
Canais de Potássio Éter-A-Go-Go
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos