1.
Bioorg Med Chem Lett
; 20(15): 4328-32, 2010 Aug 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-20609585
RESUMEN
Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells.
Asunto(s)
Fármacos Anti-VIH/química , Éteres/química , Transcriptasa Inversa del VIH/antagonistas & inhibidores , Pirazoles/química , Piridinas/química , Inhibidores de la Transcriptasa Inversa/química , Regulación Alostérica , Animales , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacocinética , Perros , Éteres/síntesis química , Éteres/farmacocinética , Transcriptasa Inversa del VIH/genética , Transcriptasa Inversa del VIH/metabolismo , Humanos , Mutación , Pirazoles/síntesis química , Pirazoles/farmacocinética , Piridinas/síntesis química , Piridinas/farmacocinética , Ratas , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/farmacocinética , Relación Estructura-Actividad
2.
Bioorg Med Chem Lett
; 18(9): 2959-66, 2008 May 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18396399
RESUMEN
Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.