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有机化学
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有机化学 ›› 2004, Vol. 24 ›› Issue (12): 1587-1594. 上一篇    下一篇

研究论文

N-取代-3-吲哚乙酰胺类α1-肾上腺素受体拮抗剂的设计、合成及其3D-QSAR研究

吴斌*,a, 李敏勇b, 江振洲c, 夏霖b   

  1. a南京医科大学药学院 南京 210029
    b中国药科大学药物化学教研室 南京 210009
    c中国药科大学新中新药研究开发中心 南京 210038
  • 收稿日期:2004-06-29 修回日期:2004-10-12 接受日期:2004-11-01 发布日期:2022-09-20
  • 基金资助:
    国家863基金(No. 2002AA2Z3131)资助项目

Design, Synthesis and 3D-QSAR Study of N-Substituted-3-indolyl-acetamide Series as α1-Adrenoceptor Antagonists

WU Bin*,a, LI Min-Yongb, JIANG Zhen-Zhouc, XIA Linb   

  1. aSchool of Pharmacy, Nanjing Medical University, Nanjing 210029
    bDepartment of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009
    cXinzhong New Drug Research and Development Center, China PharmaceuticalUniversity, Nanjing 210038
  • Received:2004-06-29 Revised:2004-10-12 Accepted:2004-11-01 Published:2022-09-20
  • Contact: *E-mail: zhaoym@nic.bmi.ac.cn

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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,设计合成了一系列N-取代-3-吲哚乙酰胺类化合物,并评价其α1-受体拮抗作用.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.并应用SOMFA方法进行分子结构特征和α1-受体生物活性之间的关系研究.

关键词: 3-吲哚乙酰胺, 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

A series of N-substituted-3-indolylacetamide derivatives were designedand synthesized based on the structure and activity relationship (SAR) of α1-adrenoceptor (α1-AR) antagonists and the biophore established bycomputer-aideddrug design (CADD), and then their antagonism at α1-adrenoceptor was evaluated.Preliminary bioassay suggested that most of the target compounds display good blocking activity to α1-AR. The correlation between the molecular structural characteristics and the α1-adrenoceptor biological activities was studied by using self-organizing molecular field analysis (SOMFA).

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