title: Design, synthesis, and biological evaluation of novel 2-methylpiperazine derivatives as potent CCR5 antagonists.
abstract: Three series of novel 2-methylpiperazine derivatives were designed and synthesized using a fragment-assembly strategy. Among them, six compounds (13, 16, 18, 22, 33, and 36) showed potent activity against CCR5 comparable to that of the positive control, maraviroc, in calcium mobilization assay. Moreover, some compounds were selected and further tested for their antiviral activity in HIV-1 single cycle assay. As a result, four compounds (13, 16, 33, and 36) showed antiviral activity at the nanomolar level. Additionally, the potent four compounds showed no cytotoxicity at a concentration of 10μM.
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Suwen
authors: S
authors: Hu
authors: State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Zhilong
authors: Z
authors: Wang
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China.
authors: Tingjun
authors: T
authors: Hou
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Xiaodong
authors: X
authors: Ma
authors: State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Jing
authors: J
authors: Li
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: Lt601@zju.edu.cn.
authors: Tao
authors: T
authors: Liu
authors: State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xxie@mail.shcnc.ac.cn.
authors: Xin
authors: X
authors: Xie
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: huyz@zju.edu.cn.
authors: Yongzhou
authors: Y
authors: Hu
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000187:drug effects*
chemical_list: C435643:2-methyl piperazine; D019380:Anti-HIV Agents; C584933:CCR5 protein, human; D010879:Piperazines; D019713:Receptors, CCR5
keywords: 2-Methylpiperazine derivatives; Anti-HIV-1 agent; CCR5 antagonist