Three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） is used to describe the chemical structures of polychlorinated naphthalenes（PCNs）.After variable screening by stepwise multiple regressio...Three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） is used to describe the chemical structures of polychlorinated naphthalenes（PCNs）.After variable screening by stepwise multiple regression（SMR） technique,the liner relationships between gas-chromatographic relative retention time（RRT）,298 K supercooled liquid pressures（logPL）,n-octanol/air partition coefficient（logKOA）,n-octanol/water partition coefficient（logKOW）,aqueous solubilities（logSW）,relative in vitro potency values（-logEROD） of PCNs and 3D-HoVAIF descriptors have been established by partial least-square（PLS） regression.The result shows that the 3D-HoVAIF descriptors can be well used to express the quantitative structure-property（activity） relationships of PCNs.Predictive capability of the models has also been demonstrated by leave-one-out cross-validation.Moreover,the predicted values have been presented for those PCNs which are lack of experimentally physico-chemical properties and biological activity by the optimum models.展开更多
使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮...使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮类抑制剂。结果表明,建立的CoMFA(q^(2)=0.926,r^(2)=0.997,r^(2)_(pred)=0.744)和CoMSIA(q^(2)=0.939,r^(2)=0.991,r^(2)_(pred)=0.786)模型具有较好的预测能力,基于这些模型设计的7个新喹啉酮类BRD4抑制剂具有高活性,并对其进行ADMET性质评价和类药性分析。以上研究结果有助于改造和开发更加有效的喹啉酮类BRD4抑制剂。展开更多
基金supported by the Ministry of Science and Technology of China (2010DFA32680)the National Natural Science Foundation of China (21005062)the Fundamental Research Funds for the Central Universities (CDJRC10220010)
文摘Three-dimensional holographic vector of atomic interaction field（3D-HoVAIF） is used to describe the chemical structures of polychlorinated naphthalenes（PCNs）.After variable screening by stepwise multiple regression（SMR） technique,the liner relationships between gas-chromatographic relative retention time（RRT）,298 K supercooled liquid pressures（logPL）,n-octanol/air partition coefficient（logKOA）,n-octanol/water partition coefficient（logKOW）,aqueous solubilities（logSW）,relative in vitro potency values（-logEROD） of PCNs and 3D-HoVAIF descriptors have been established by partial least-square（PLS） regression.The result shows that the 3D-HoVAIF descriptors can be well used to express the quantitative structure-property（activity） relationships of PCNs.Predictive capability of the models has also been demonstrated by leave-one-out cross-validation.Moreover,the predicted values have been presented for those PCNs which are lack of experimentally physico-chemical properties and biological activity by the optimum models.
文摘使用比较分子力场分析法(CoMFA)和比较分子相似性指数法(CoMSIA)对33个已报道的喹啉酮类BRD4抑制剂进行3D-QSAR模型建立,研究了其化学结构和生物活性间的关系,并用计算机辅助药物设计(computer-aided drug design,CADD)设计出7个喹啉酮类抑制剂。结果表明,建立的CoMFA(q^(2)=0.926,r^(2)=0.997,r^(2)_(pred)=0.744)和CoMSIA(q^(2)=0.939,r^(2)=0.991,r^(2)_(pred)=0.786)模型具有较好的预测能力,基于这些模型设计的7个新喹啉酮类BRD4抑制剂具有高活性,并对其进行ADMET性质评价和类药性分析。以上研究结果有助于改造和开发更加有效的喹啉酮类BRD4抑制剂。
