RESUMEN
We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based assay system leading to the discovery of aryl-substituted TTPM derivatives (38, 44, and 45), which exhibited significant inhibition of HIV-1 replication with acceptable safety margins. These novel and potent TTPMs could serve as leads for further development.
Asunto(s)
Fármacos Anti-VIH/síntesis química , VIH-1/metabolismo , Pirimidinas/química , Triazoles/química , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Línea Celular , Evaluación Preclínica de Medicamentos , VIH-1/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento , Humanos , Pirimidinas/síntesis química , Pirimidinas/farmacología , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
We describe a novel 7-aminopyrazolo[1,5-a]pyrimidine (7-APP) derivative as a potent hepatitis C virus (HCV) inhibitor. A series of 7-APPs was synthesized and evaluated for inhibitory activity against HCV in different cell culture systems. The synthesis and preliminary structure-activity relationship study of 7-APP are reported.