1.
Bioorg Med Chem Lett
; 20(10): 3116-9, 2010 May 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-20417098
RESUMEN
Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.
Asunto(s)
Fármacos Anti-VIH/química , Benzamidas/química , Antagonistas de los Receptores CCR5 , Inhibidores de Fusión de VIH/química , Pirroles/química , Animales , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacocinética , Benzamidas/síntesis química , Benzamidas/farmacología , Inhibidores de Fusión de VIH/síntesis química , Inhibidores de Fusión de VIH/farmacocinética , Humanos , Microsomas Hepáticos/metabolismo , Pirroles/síntesis química , Pirroles/farmacocinética , Ratas , Receptores CCR5/metabolismo , Relación Estructura-Actividad
2.
Bioorg Med Chem Lett
; 19(18): 5401-6, 2009 Sep 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-19674898
RESUMEN
A novel series of CCR5 antagonists has been identified, utilizing leads from high-throughput screening which were further modified based on insights from competitor molecules. Lead optimization was pursued by balancing opposing trends of metabolic stability and potency. Selective and potent analogs with good pharmacokinetic properties were successfully developed.