HIV-1逆转录酶抑制剂的三维定量构效关系

采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)对一系列非核苷类HIV-1逆转录酶抑制剂(苯磺酰基亚胺噻唑类化合物)进行了三维定量构效关系的研究,获得了高可靠性的CoMFA和CoMSIA模型,其交叉验证相关系数q2值分别为0.748和0.607.通过对CoMFA和CoMSIA模型三维等势图的分析,确定了该类化合物抗HIV-1活性的结构要求.研究结果表明,对苯磺酰基亚胺噻唑类化合物而言,在苯环的C-5位引入体积大和电负性强的基团能增加其抑制活性;苯环的C-2位的氢键给体基团对活性有利;噻唑环的R2取代基疏水性增大会降低生物活性.研究结果表明,可以指导新HIV-1逆转录酶抑制剂的设计和合成.     

HIV-1逆转录酶抑制剂2-氨基6-苯磺酰基苄腈及其类似物活性OSAR研究

首先利用半经验AM I量子化学方法计算了54个2-氨基-6-苯磺酰基苄腈及其类似物的物理化学、电子结构、指示变量等共28个参数,然后使用偏最小二乘,穷举回归和混沌遗传乘法训练的人工神经网络方法建立了这些参数和其抑制H IV-1逆转录酶活性之间的定量构效关系模型,为设计、合成更高生物活性的该类化合物提供了理论参考。     

Screening of new non-nucleoside reverse transcriptase inhibitors of HIV-1 based on traditional Chinese medicines database

HIV-1 RT is an important target for the treatment of AIDS.There are two major classes of antiviral agents that inhibit HIV-1 RT have been identified,nucleoside RT inhibitors(NRTIs) and non-nucleoside RT inhibitors(NNRTIs).In this report,a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database (TCMD) using a combination of virtual screening,docking,molecular dynamic simulations,where results were ranked by scoring function of...     

Pyridazines 92. Synthesis of dialkyldipyridazinodiazepinones as potential HIV‐1 reverse transcriptase inhibitors

Two methods for the preparation of dialkylsubstituted dipyridazino[4,3‐b:3′,4′‐e][1,4]diazepinones and dipyridazino[3,4‐b:3′,4′‐e][1,4]diazepinones are reported. The new compounds were evaluated for their inhibitory effects against the replication of human immunodeficiency virus [HIV‐1(III_B) and HIV‐2(ROD)] in MT‐4 cells.