Chen B K, Horváth C, Bertino J R
J Med Chem. 1979 May;22(5):483-91. doi: 10.1021/jm00191a005.
Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained with 50 quinazolines were similar. On the other hand, for the inhibition of thymidylate synthetase from murine L1210S cells and from Lactobacillus casei, QSAR's formulated on the basis of data measured with 33 compounds were different, indicating that the two enzymes are dissimilar. The use of multivariate statistics including cluster analysis, factor analysis, and discriminant analysis is shown to facilitate the formulation of a satisfactory correlation equation. The procedure is demonstrated by the development of QSAR for the inhibition of thymidylate synthetase.
已经建立了2,4-二氨基喹唑啉-谷氨酸类似物对二氢叶酸还原酶和胸苷酸合成酶抑制作用的定量构效关系（QSAR）。对于来自人类急性淋巴细胞白血病细胞和小鼠L1210R细胞的二氢叶酸还原酶，用50种喹唑啉获得的QSAR相似。另一方面，对于来自小鼠L1210S细胞和干酪乳杆菌的胸苷酸合成酶抑制作用，基于用33种化合物测得的数据制定的QSAR不同，表明这两种酶不同。结果表明，使用包括聚类分析、因子分析和判别分析在内的多元统计方法有助于建立令人满意的相关方程。通过开发胸苷酸合成酶抑制作用的QSAR来证明该程序。
