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构象限制策略在药物设计中的应用

吴国丽, 卢晓林, 许晋芳

吴国丽, 卢晓林, 许晋芳. 构象限制策略在药物设计中的应用[J]. 中国药科大学学报, 2020, 51(3): 357-367. DOI: 10.11665/j.issn.1000-5048.20200314
引用本文: 吴国丽, 卢晓林, 许晋芳. 构象限制策略在药物设计中的应用[J]. 中国药科大学学报, 2020, 51(3): 357-367. DOI: 10.11665/j.issn.1000-5048.20200314
WU Guoli, LU Xiaolin, XU Jinfang. Application of a conformational restriction strategy in drug design[J]. Journal of China Pharmaceutical University, 2020, 51(3): 357-367. DOI: 10.11665/j.issn.1000-5048.20200314
Citation: WU Guoli, LU Xiaolin, XU Jinfang. Application of a conformational restriction strategy in drug design[J]. Journal of China Pharmaceutical University, 2020, 51(3): 357-367. DOI: 10.11665/j.issn.1000-5048.20200314

构象限制策略在药物设计中的应用

基金项目: 国家自然科学基金资助项目(No. 31700306)

Application of a conformational restriction strategy in drug design

Funds: This study was supported by the National Natural Science Foundation of China (No. 31700306)
  • 摘要: 在药物分子设计中,构象限制已成为先导化合物结构优化中重要的改造策略之一。本文综述了一些合理增加分子构象限制的应用实例。通过在分子中引入稠合环、大环、螺环、环丙基、桥环、甲基等结构,展示了构象限制策略在改善药代动力学性质、提高化合物的活性和选择性,以及增加化合物新颖性等方面的广泛应用。通过运用这些构象限制策略,能够显著改善先导化合物的成药性,以期能够为创新药物的设计与开发提供理论指导和实践经验。
    Abstract: Conformational restriction has become one of the important strategies for modification and optimization of lead compounds in structure-based drug design. In this review, we select some recent practical examples from literature to present applications of conformational restriction in structure-based drug design. By introducing fused rings, macrocycles, spiral rings, cyclopropyl groups, bridging rings, methyl groups into molecules, we can find that the conformational restriction strategy is widely used in improving pharmacokinetic properties, enhancing the activity and selectivity, and increasing the novelty of compounds. By using these conformational restriction strategies, the drug-like properties of lead compounds can be significantly improved. This paper can help to provide theoretical guidance and practical experience for innovation in drug design and development.
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出版历程
  • 收稿日期:  2019-08-21
  • 修回日期:  2020-05-12
  • 刊出日期:  2020-06-24

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