Design, Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists

Abstract

By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC50 values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC50 value of 6.29 μM and an anti-HIV-1 inhibitor with an IC50 value of 0.44 μM. © 2013 Liu et al.