| 冯长君,何红梅,李靖.化学通报,2019,82(10):946-949. |
| 新型三唑并噻二唑衍生物抑制活性CoMFA模型 |
| CoMFA Model of Inhibitory Activity for Novel Triazol-ethiadiazole Derivatives |
| 投稿时间：2019-04-25 修订日期：2019-07-26 |
| DOI： |
| 中文关键词: 新型三唑并噻二唑衍生物 PTP1B 抑制活性 比较分子力场分析 三维定量构效关系 |
| 英文关键词:novel triazol-ethiadiazole derivative protein tyrosine phosphatase 1B inhibitory activity comparative molecular field analysis three dimensional quantitative structure-activity relationship |
| 基金项目:国家自然科学基金(21075138)、江苏省自然科学基金(BK20171168)和结构化学国家重点实验室开放基金(2016003)资助 |
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| 中文摘要: |
| 基于比较分子力场分析(CoMFA)方法建立21种新型三唑并噻二唑衍生物对PTP1B的抑制活性(pMP)的三维定量构效关系(3D-QSAR)。训练集中17个化合物用于建立预测模型，测试集5个化合物作为模型验证。已建立的CoMFA模型的交叉验证系数(Rcv2)、非交叉验证系数(R2)分别为0.432、0.975，说明所建模型具有较强的稳定性和良好的预测能力。该模型中立体场、静电场贡献率依次为59.2%、40.8%，表明影响抑制活性(pMP)的主要因素是取代基的空间位阻及疏水性，其次是取代基的氢键及配位作用。基于此研究结果，设计了3个具有较高抑制活性的新化合物，有待医学实验验证。 |
| 英文摘要: |
| Based on the comparative molecular field analysis(CoMFA) method, three dimensional quantitative structure-activity relationships(3D-QSAR) between the molecular structures and their inhibitory activities (pMP) of 21 novel triazol-ethiadiazole derivatives against PTP1B(protein tyrosine phosphatase 1B) were established. 17 compounds in the training set were served to build the predicting model, and the test set of five compounds were used to validate the model. The coefficients of the cross-validation (Rcv2) and non cross-validation (R2) for CoMFA model established in this study were 0.432 and 0.975, respectively. The results showed that the model had strong stability and good predictability．In this model，the contributions of the steric and electrostatic fields were 59.2% and 40.8%，respectively. It is shown that the main factors affecting the inhibitory activity (pMP) are steric hindrance and hydrophobicity of substituents, followed by hydrogen bonding and coordination of substituents. Base on the results and discussion, we also designed three novel molecules with satisfied predictions activity for the the further experimental validation. |
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