HEPT类化合物抗艾滋病活性的定量构效关系研究

Quantitative structure-activity relationship study on HEPT compounds for antiaids

利用半经验量子化学PM3方法计算了106个HEPT类化合物的优势构象以及物理化学和电子结构等参数,讨论了该类化合物的这些参数对HIV-1逆转录酶抑制剂活性的影响,利用穷举回归、偏最小二乘和混沌遗传算法训练的人工神经网络方法建立了物理化学、电子结构等参数和其抑制HIV-1逆转录酶活性之间的定量结构活性关系模型。结果表明:(1)较大的logP、较高的最低空轨道能、较小的分子量均有利于提高该类化合物的抗HIV-1活性;(2)当该类化合物有适当大小的 R1取代基、C-6位苯环的间位被疏水性集团取代时该类化合物有较高的抗HIV-1生物活性。

1-[（2-hydroxyethoxy） methyl]-6-（phenyhhio）-thymine and its analogues as HIV-1 Reverse Transcriptase Inhibitors were calculated using the Semi-empirical Quantum Chemistry Method PM3. QSAR studies have been approached based on Physieoehemieal, Quantum ehemistieal etc. parameters, using PLS, exhaustion regression and ANN trained by chaos map aided GA. The activities of 1-[（2-hydroxyethoxy） methyl]-6-（phenyhhio）-thymine and congeners will increase due to the larger logP, the energy of the lowest unoccupied molecular orbital ELUMO, the lower molecular weight; anti-HIV activities of 1-[（2-hydroxyethoxy） methyl]-6-（phenylthio）-thymine and congeners will increase by the attachment of hydrophobic group to the C-3＇ and C-5＇ positions of the Phenyl of R2 group and propriety bulk R2 group.