大麻素Ⅰ型受体拮抗剂的结构特征  

Structural Characteristics of Cannabinoid Type Ⅰ Receptor Antagonists

作　　者：林克江[1] 黄振桂[1] 李婷[2] 王南溪[2] 程瑶[2] 沈玲玲[2] 王宇彤[2] 李卉[2] 叶波平[3] 

机构地区：[1]中国药科大学药学院,南京210009 [2]中国药科大学基础药学理科基地班,南京210009 [3]中国药科大学生命科学与技术学院,南京210009

出　　处：《高等学校化学学报》2013年第5期1240-1245,共6页Chemical Journal of Chinese Universities

基　　金：国家'重大新药创制'科技重大专项基金(批准号:2012ZX09103301-018)资助

摘　　要：以92个具有大麻素受体Ⅰ(CB1)拮抗活性的化合物为训练集,39个化合物为测试集,采用DiscoveryStudio V2.5(DS)软件中的3D构效关系药效团产生(QSAR Pharmacophore Generation)模块建立药效团模型.获得的最佳药效团模型的构成为一个氢键受体(HBA)、一个疏水基团(HY)和二个芳环中心(RA),采用费用函数(Cost function)评价药效团模型,该模型的Δcost为119.32,相关性为0.921,均方根偏差为0.730,Configuration cost为16.1229,表明模型能较好地预测化合物的活性.同时针对目前已知的近450个化合物的12种结构类型进行了探讨,所得结果为进一步设计CB1拮抗剂提供了理论依据.Cannabinoid type I receptor（ CB1 ） antagonists offer a new approach to treat obesity and problems related to obesity such as diabetes and cardiometabolic risks. Pharmacophore models were developed via Dis-eovery Studio V2. 5 with a training set of 92 CB1 agonists and a test set of 39 compounds. The best hypothesis consisting of five features, namely, a hydrogen bond acceptors, a hydrophobic and two ring aromatic features, has a correlation coefficient of 0. 921, a cost difference of 119. 132, the root mean square（RMS） of 0. 730, and a configuration cost of 16. 1229, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of the near 450 known CB1 aonists in 12 structural tvoes and orovides a zuide to desizn new CB1 antagonists.

关 键 词：大麻素Ⅰ型受体拮抗剂 药效团 定量构效关系 

分 类 号：O641.3[理学—物理化学]