Discovery of a new HIV-1 inhibitor scaffold and synthesis of potential prodrugs of indazoles.
Bioorg Med Chem Lett
; 23(10): 2888-92, 2013 May 15.
Article
en En
| MEDLINE
| ID: mdl-23566519
A new oxazole scaffold showing great promise in HIV-1 inhibition has been discovered by cell-based screening of an in-house library and scaffold modification. Follow-up SAR study focusing on the 5-aryl substituent of the oxazole core has identified 4k (EC50=0.42µM, TI=50) as a potent inhibitor. However, the analogues suffered from poor aqueous solubility. To address this issue, we have developed broadly applicable potential prodrugs of indazoles. Among them, N-acyloxymethyl analogue 11b displayed promising results (i.e., increased aqueous solubility and susceptibility to enzymatic hydrolysis). Further studies are warranted to fully evaluate the analogues as the potential prodrugs with improved physiochemical and PK properties.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
/
VIH-1
/
Fármacos Anti-VIH
/
Descubrimiento de Drogas
/
Indazoles
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido