Rational design of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase.
J Med Chem
; 55(23): 10601-9, 2012 Dec 13.
Article
em En
| MEDLINE
| ID: mdl-23137340
ABSTRACT
A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, including a structure of the Y188L RT protein, was used extensively to help identify and optimize the key hydrogen-bonding motif. This led directly to the design of compound 43 that exhibits remarkable antiviral activity (EC50<1 nM) against a wide range of NNRTI-resistant viruses and a favorable pharmacokinetic profile across multiple species.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Inibidores da Transcriptase Reversa
/
Transcriptase Reversa do HIV
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article