非肽类凝血酶抑制剂的比较分子力场分析

在血栓症和止血疗法中凝血酶起重要的生物调节作用，凝血酶抑制剂由于基溶 血栓作用成为药物设计的热点，对非肽类芳基磺酸酯系列凝血酶抑制剂进行了三维 定量构效关系研究。用Autodock方法和比较分子力场分析相结合构建了该类分子的 定量构效关系模型，得到三维等值线图。模型的传统相关系数r~2=0.956，交叉验 证系数q~2=0.681, F_(4,16) = 85.985，标准偏差S = 0.158。该模型为凝血酶抑 制剂的进一步结构改造提供了有益的启示。

Comparative Molecular Field Analysis of Non-peptidic Inhibitors of Thrombin

Thrombin is a trypsin-like serine proteinase that plays a crucial role in the processes of thrombosis and haemostasis. The three-dimensional quantitative structure activity relationship for a series of reported arylsulfonate based non-peptidic thrombin inhibitors by comparative molecular field analysis have been studied. One representative compound of the series was docked onto thrombin (PDB code: 1UVT) by using Autodock program to determine the most likely binding conformation to thrombin. The strategy of all-orientation search (AOS) and all-placement search (APS) were used in the CoMFA study to give a final model with q2 = 0.681, r2 = 0.956, S = 0.158, and F4,16 = 85.985. The analysis of the CoMFA coefficients map gives insights to the design of better thrombin inhibitors.