苯并咪唑-5-羧酸酰胺HCV NS5B聚合酶抑制剂的分子全息QSAR研究及设计  

HQSAR study and design of benzimidazole 5-carboxylic amide derivatives as HCV NS5B polymerase inhibitors

作　　者：陈娴 张廉高 王子恒 王月平[2] 何严萍[1] 

机构地区：[1]云南大学教育部自然资源药物化学重点实验室,化学科学与工程学院·药学院,云南昆明650091 [2]昆明理工大学理学院应用化学系,云南昆明650500

出　　处：《云南大学学报（自然科学版）》2017年第6期1040-1050,共11页Journal of Yunnan University(Natural Sciences Edition)

基　　金：国家自然科学基金(21262044,21362017)

摘　　要：采用分子全息定量构效关系(HQSAR)方法,研究54个苯并咪唑-5-羧酸酰胺类HCV NS5B聚合酶抑制剂的结构与活性之间的关系.讨论了分子碎片大小、碎片区分参数以及分子全息长度对模型的影响.以39个化合物构成的训练集所建最优模型的交叉验证相关系数q2为0.779,非交叉验证相关系数r2为0.922,标准偏差SEE为0.251.同时,利用HQSAR模型的色码图探讨了对该类抑制剂的活性起重要作用的结构片段,并根据HQSAR最佳模型图设计了17个新型2-硫乙酰芳胺-苯并咪唑-5-羧酸酰胺类衍生物,经HQSAR模型预测,这些分子理论上对HCV NS5B聚合酶均具有良好的抑制活性.A hologram quantitative structure-activity relationship （HQSAR） studies were conducted on a se- ries of 54 benzimidazole 5-carboxylic amide derivatives as HCV NS5B polymerase inhibitors.The influences of molecular fragment parameter, fragment distinction parameter and molecular holographic length on the HQSAR models were investigated. The optimal HQSAR model was obtained for the 39 training set compounds showing cross-validated q2 value of 0.779, conventional rE value of 0.922 and stand deviation SEE value of 0.251.The col- or code analysis based on the obtained HQSAR model provided useful insights into the chemical and structural features of these inhibitors for their NS5B polymerase inhibitory potency.Based on the best model HQSAR, 17 new 2-sulfur acetyl aromatic aminebenzimidazole-5-carboxylic acid amide derivatives were designed and screened u- sing the optimal HQSAR model, giving potential candidates with high predictive HCV NS5B polymerases inhibito- ry activity.

关 键 词：苯并咪唑-5-羧酸酰胺 HCV NS5B聚合酶抑制剂 分子全息定量构效关系 色码 分子设计 

分 类 号：O6-04[理学—化学]