Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the S3 pocket.
Bioorg Med Chem Lett
; 21(16): 4836-43, 2011 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-21741239
ABSTRACT
Structure-based design led to the discovery of a novel class of renin inhibitors in which an unprecedented phenyl ring filling the S1 site is attached to the phenyl ring filling the S3 pocket. Optimization for several parameters including potency in the presence of human plasma, selectivity against CYP3A4 inhibition and improved rat oral bioavailability led to the identification of 8d which demonstrated antihypertensive efficacy in a transgenic rat model of human hypertension.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Éteres Fenílicos
/
Renina
/
Inhibidores Enzimáticos
/
Antihipertensivos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos