title: 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 IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.
authors: Zhejiang University-École Normale Supérieure Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Lt601@zju.edu.cn
authors: Tao
authors: T
authors: Liu
authors: Zhiyong
authors: Z
authors: Weng
authors: Xiaowu
authors: X
authors: Dong
authors: Linjie
authors: L
authors: Chen
authors: Ling
authors: L
authors: Ma
authors: Shan
authors: S
authors: Cen
authors: Naiming
authors: N
authors: Zhou
authors: Yongzhou
authors: Y
authors: Hu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001681:Biological Assay; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D002459:Cell Fusion; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D015870:Gene Expression; D017930:Genes, Reporter; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010879:Piperazines; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1; D008156:Luciferases