中文摘要：

5-N,N-二取代5-氨基吡唑-3-羧酸、3-硝基-4-氨基苯甲酸和6-氨基烟酸类化合物是G蛋白偶联受体109B（GPR109B）潜在生物活性药物。本实验采用比较分子力场分析法（Co MFA）和比较分子相似性指数分析法（Co MSIA）分别建立46个GPR109B激动剂分子的3D-QSAR模型,确定此类G蛋白偶联受体激动剂的分子结构与生物活性之间的定量关系。Co MFA模型的训练集抽一法交叉验证系数q^2=0.472,非交叉验证系数r^2=0.92,标准偏差SE=0.212;CoMSIA模型的训练集抽一法交叉验证系数q^2=0.498,非交叉验证系数r^2=0.803,标准偏差SE=0.332。两个3D-QSAR模型预测数值与实验数据基本一致,显示模型具有较好的预测能力。本实验根据CoMFA和CoMSIA模型所提供的立体场、静电场、氢键给体场等信息进一步提出改善此类激动剂生物活性的药物设计思路。

英文摘要：

5-N,N-Disubstituted 5-aminopyrazole-3-carboxylic acids, 3-Nitro-4-amino benzoic acids and 6-amino nicotinic acids are potential drugs of GPRI09B which have obvious biological activity. Establishing G-protein coupled receptor agonists 3D-QSAR models and confirming the quantitative relationship between the molecular structure and the biological activity of such agonists were performed by using comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA） after molecular alignment. The final LOO （Leave-one-out） cross-validation coefficient（q^2） of CoMFA model is 0.472, correlation coefficient （r^2） is 0.92, standard deviation （SE） is 0.212; the final decision coefficient（q^2） of CoMSIA model is 0.498, non-cross-validation coefficient （r^2） is 0.803, standard deviation （SE） is 0.212. Correlation value indicates that the model has good predictive ability. According to the steric, electrostatic and hydrogen-bond donor fields of CoMFA and CoMSIA, the potential new agonist with higher biological activity can be designed for further research.