Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (12): 3282-3288.DOI: 10.6023/cjoc201707001 Previous Articles     Next Articles

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含1-[4-二(4-氟苯)甲基]哌嗪基团的异噁唑的设计合成及抗肿瘤活性研究

丁勇, 李清寒, 赵志刚, 杨学军, 陈峰   

  1. 西南民族大学化学与环境保护工程学院 成都 610041
  • 收稿日期:2017-07-02 修回日期:2017-08-19 出版日期:2017-12-25 发布日期:2017-09-15
  • 通讯作者: 李清寒 E-mail:lqhchem@163.com
  • 基金资助:

    四川省科技厅科技支撑计划(No.2015NZ0033)资助项目.

Design, Synthesis and Anti-tumor Activity Evaluation of a Novel Series of Isoxazoles Bearing (1-Bi(4-fluorophenyl)methyl)-piperazine Unit

Ding Yong, Li Qinghan, Zhao Zhigang, Yang Xuejun, Chen Feng   

  1. College of Chemistry and Environmental Protection Engineering, Southwest Minzu University, Chengdu 610041
  • Received:2017-07-02 Revised:2017-08-19 Online:2017-12-25 Published:2017-09-15
  • Contact: 10.6023/cjoc201707001 E-mail:lqhchem@163.com
  • Supported by:

    Project supported by the Sichuan Provincial Department of Science and Technology Support Program (No. 2015NZ0033).

Twelve novel isoxazoles containing (1-bi(4-fluorophenyl)methyl)piperazine unit were prepared in two steps starting from propargyl bromide, (1-bi(4-fluorophenyl)methyl)piperazine and hydroxymoyl chlorides with moderate yield (21%~76%). The structures of the new compounds were characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis, and their in vitro anti-tumor activity was screened. The bioactive assay for the newly prepared compounds manifested that ten newly isoxazole derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 μg/mL with inhibition of 64.15%~95.87% and IC50 of 35.62~13.67 μg/mL. Four isoxazoles exhibited good to excellent inhibitory activity against Leukemia cell HL-60 in 40 μmol/L (IC50:36.51~15.25 μg/mL), 2-(2-fluorophenyl)-5-(1-(bi-(4-fluorophenyl)methyl)-piperazine)methylisoxazole (5g) and 2-(4-fluorophenyl)-5-(1-(bi-(4-fluorophenyl)methyl)piperazine)methylisoxazole (5h) exhibited good to excellent inhibitory activity against Lung cancer cell A-549 (IC50 value up to 21.09 and 35.36 μg/mL, respectively).

Key words: 1-[bi(4-fluorophenyl)methyl]piperazine, isoxazole, organic synthesis, anti-tumor activity