Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase.
Bioorg Med Chem Lett
; 19(20): 5864-8, 2009 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-19758802
ABSTRACT
A series of potent nicotinamide inhibitors of soluble epoxides hydrolase (sEH) is disclosed. This series was designed using structure-based deconstruction and a combination of two HTS hit series, resulting in hybrid analogs that retained the optimal potency from one series, and acceptable in vitro metabolic stability from the other. Structure-guided optimization of these analogs gave rise to nanomolar inhibitors of human sEH that had acceptable plasma exposure to qualify them as probes to determine the in vivo phenotypic consequences of sEH inhibition.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Niacinamida
/
Inhibidores Enzimáticos
/
Epóxido Hidrolasas
/
Antiinflamatorios
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos