Design,Synthesis and Biological Evaluation of Novel Piperazine Derivatives as CCR5 Antagonists |
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| Authors: | Tao Liu Zhiyong Weng Xiaowu Dong Linjie Chen Ling Ma Shan Cen Naiming Zhou Yongzhou Hu |
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| Affiliation: | 1. Zhejiang University-École Normale Supérieure Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.; 2. Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.; 3. Insititute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.; 4. Peking Union Medical College, Beijing, China.; McGill University AIDS Centre, Canada, |
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| 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. |
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