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化学学报
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化学学报 ›› 2004, Vol. 62 ›› Issue (15): 1430-1436. 上一篇    下一篇

研究论文

芳氧烷基哌嗪苯并噁唑类α1-受体拮抗剂的设计、合成及其3D-QSAR研究

吴斌1, 李敏勇2, 江振洲3, 夏霖2   

  1. 1. 南京医科大学药学院, 南京, 210029;
    2. 中国药科大学药物化学教研室, 南京, 210009;
    3. 中国药科大学新中新药研究开发中心, 南京, 210038
  • 投稿日期:2003-10-23 修回日期:2004-02-05 发布日期:2014-02-17
  • 通讯作者: 吴斌,E-mail:jsnjcpuwubin@hotmail.com E-mail:jsnjcpuwubin@hotmail.com
  • 基金资助:
    国家科委863计划(No.2002AA2Z3118)资助项目.

Design, Synthesis and 3D-QSAR Study of 2-[N’-(2-Aryloxyethyl)-piperazinomethyl]-benzoxazole Series asα1-Adrenoceptor Antagonists

WU Bin1, LI Min-Yong2, JIANG Zhen-Zhou3, XIA Lin2   

  1. 1. School of Pharmacy, Nanjing Medical University, Nanjing 210029;
    2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009;
    3. Xinzhong New Drug Research and Development Center, China Pharmaceutical University, Nanjing 210038
  • Received:2003-10-23 Revised:2004-02-05 Published:2014-02-17

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结合α1-受体拮抗剂的构效关系和我们应用计算机辅助药物设计方法所构建的药效团模型,设计合成了17个1-(5-甲基-2-苯并噁唑甲基)-4(2-取代芳氧乙基)哌嗪类化合物,其结构均经1H NMR,IR及MS(HRMS)确证.初步生物活性测试表明,所合成的目标化合物多数具有较好的α1-受体拮抗活性.3D-QSAR研究为该类化合物的结构改造提供了理论依据.

关键词: 苯并唑, α1-受体拮抗剂, 良性前列腺增生, 三维定量构效关系, 自组织分子场分析

Seventeen 2-[N'-(2-aryloxyethyl)piperazinomethyl]-benzoxazole derivatives have been designed and synthesized based on the structure and activity relationship (SAR) of α1-adrenoceptor (α1-AR) antagonists and the results of computer-aided drug design (CADD) we studied before.All the target compounds have been identified by 1H NMR, IR and MS (HRMS).Preliminary bioassay suggests that most of the target compounds display good blocking activity to α1-AR.The 3D-QSAR study is valuable for designing and optimizing new active structures of this kind of compounds.

Key words: benzoxazole, α1-adrenoceptor antagonist, benign prostatic hyperplasia, 3D-QSAR, self-organizing molecular field analysis