Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly(ADP-ribose) polymerase (PARP) inhibitors.
Bioorg Med Chem Lett
; 20(2): 488-92, 2010 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-20007017
ABSTRACT
A potent series of substituted 2-phenyl-2H-indazole-7-carboxamides were synthesized and evaluated as inhibitors of poly (ADP-ribose) polymerase (PARP). This extensive SAR exploration culminated with the identification of substituted 5-fluoro-2-phenyl-2H-indazole-7-carboxamide analog 48 which displayed excellent PARP enzyme inhibition with IC(50)=4nM, inhibited proliferation of cancer cell lines deficient in BRCA-1 with CC(50)=42nM and showed encouraging pharmacokinetic properties in rats compared to the lead 6.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Azetidinas
/
Inhibidores Enzimáticos
/
Inhibidores de Poli(ADP-Ribosa) Polimerasas
/
Amidas
/
Indazoles
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Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia