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| 基于构效关系与分子对接的哌啶类MOR激动剂的设计 |
| Design of Piperidine MOR Agonists Based on Structure Activity Relationship and Molecular Docking |
| 投稿时间：2026-03-30 修订日期：2026-05-11 |
| DOI： |
| 中文关键词: 哌啶类MOR激动剂设计 定量构效关系 分子对接 特征结构 作用模式 |
| 英文关键词:Piperidine MOR agonists design, Quantitative structure-activity relationship, Molecular docking, Feature structure, Interaction pattern |
| 基金项目:潍坊市科技发展计划项目(2022GX020) |
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| 中文摘要: |
| μ阿片受体（μ opioid receptor, MOR）激动剂是目前缓解疼痛并减少药物副作用的重要选择。本文以系列哌啶类MOR激动剂为研究对象，通过比较分子相似性指数法和分子对接方法建立定量构效关系预测模型，研究影响化合物激动活性的特征结构信息，揭示该类激动剂与靶标之间的作用模式。结果表明，模型具有较强的预测能力（Q2=0.532，R2ncv=0.978，R2pre=0.864），三氟甲基所在的区域为立体场和静电场敏感区，酚羟基所在的区域为氢键供体有利区，羟基与氨基酸通过水分子可形成强氢键结合网络，哌啶环和二甲胺的质子化氮作为氢键受体，能够与MOR形成氢键结合。实验所得模型和信息为新型高选择性的MOR激动剂的研发提供了重要参考。 |
| 英文摘要: |
| μ Opioid receptor (MOR) agonists are crucial for pain relief while reducing drug side effects. This article focused on some piperidine-based MOR agonists, using comparative molecular similarity index and molecular docking methods to establish the quantitative structure-activity relationship prediction model. The aim was to explore the structural features influencing the activity and interaction patterns between these agonists and MOR. The results showed that the model has strong predictive ability (Q2=0.532，R2ncv=0.978，R2pre=0.864). The region located by the trifluoromethyl group is sensitive to steric and electrostatic fields. The area with the phenol group is favorable for hydrogen bond donors, and can form strong hydrogen bond network with amino acids through water molecules. The protonated nitrogen of piperidine ring and dimethylamine act as hydrogen bond acceptors, which can form hydrogen bonding with MOR. The model and insights obtained from this study provide significant guidance for the development of new, highly selective MOR agonists. |
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