Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.
J Med Chem
; 50(1): 6-9, 2007 Jan 11.
Article
en En
| MEDLINE
| ID: mdl-17201405
ABSTRACT
Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential target for the treatment of hypertension and related disorders. Indazole amide 3 was identified as a potent and selective ROCK1 inhibitor but possessed poor oral bioavailability. Optimization of this lead resulted in the discovery of a series of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead. Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability.
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Base de datos:
MEDLINE
Asunto principal:
Piridonas
/
Proteínas Serina-Treonina Quinasas
/
Péptidos y Proteínas de Señalización Intracelular
/
Amidas
/
Indazoles
/
Antihipertensivos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos