1，2-萘醌类化合物抑制PTP1B的三维定量构效关系研究  

3D-QSAR Analyses of 1,2-Naphthoquinone Derivatives Inhibiting PTP1B

作　　者：于倩[1] 李艳妮[1] 葛志强[1] 

机构地区：[1]天津大学化工学院制药工程系,天津300072

出　　处：《化学学报》2008年第2期188-194,共7页Acta Chimica Sinica

摘　　要：蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B,PTP-1B)是近年来发现的治疗Ⅱ型糖尿病的新靶点,1,2-萘醌类化合物对PTP-1B有较好的抑制活性,具有良好的药用前景.为了设计出本类化合物抑制效果更好的分子构型,用比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)对该类化合物进行了三维定量构效关系(3D-QSAR)的研究,并建立了相关的预测模型.其中,CoMFA模型的交叉验证相关系数(q^2)为0.555,非交叉验证相关系数(r^2)为0.991,标准偏差(SEE)为0.049,F值为564.910.CoMSIA模型的q^2为0.558,r^2为0.991,SEE为0.050,F值为542.773.计算结果表明,获得的CoMFA和CoMSIA模型具有良好的预测能力,可以应用于指导该类化合物的设计.Protein tyrosine phosphatase 1B （PTP-1B）, has been implicated as a negative regulator of insulin receptor signaling. 1,2-Naphthoquinone skeleton was discovered as a hit toward the, PTP-1B inhibitor. Here, 3D-QSAR and molecular modeling was performed on a series of 1,2-naphthoquinone derivatives. Thirty-two compounds were served to establish the model, which was validated by evaluation of an external set of 4 compounds. The best predictions were obtained with the CoMFA steric, electrostatic fields （leave-one-out q^2=0.555, no validation r^2=0.991, standard error of estimate=0.049, F=564.910）, and with the CoMSIA combined steric, electrostatic, and lipophilic fields （leave-one-out q^2=0.558, no validation r^2=0.991, standard error of estimate=0.050, F=542.773）. The 3D-QSAR model was then superim- posed to the PTP-1B active site, giving direct contour maps of the different fields.

关 键 词：1 2-萘醌 三维定量构效关系 蛋白酪氨酸磷酸酶1B 

分 类 号：TQ460.1[化学工程—制药化工]