Novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 7. 8-Arylethyldipyridodiazepinones as potent broad-spectrum inhibitors of wild-type and mutant enzymes.
J Med Chem
; 41(16): 2960-71, 1998 Jul 30.
Article
en En
| MEDLINE
| ID: mdl-9685235
ABSTRACT
Like other nonnucleoside inhibitors of HIV-1 reverse transcriptase, the dipyridodiazepinone nevirapine (Viramune, 1) selects for drug resistant variants of HIV-1, both in cell culture and in patients. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. Several analogues of this series display good broad spectrum potency against a panel of mutant enzymes.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Piridinas
/
Azepinas
/
Inhibidores de la Transcriptasa Inversa
/
Transcriptasa Inversa del VIH
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos