定量构效关系。5-（取代苄基）-2,4-二氨基嘧啶对大肠杆菌和牛肝二氢叶酸还原酶抑制作用的比较。
Quantitative structure-selectivity relationships. Comparison of the inhibition of Escherichia coli and bovine liver dihydrofolate reductase by 5-(substituted-benzyl)-2,4-diaminopyrimidines.
作者信息
Li R L, Dietrich S W, Hansch C
出版信息
J Med Chem. 1981 May;24(5):538-44. doi: 10.1021/jm00137a012.
In our previous publication (Blaney, J. M.; Dietrich, S. W.; Reynolds, M. A.; Hansch, C. J. Med. Chem. 1979, 22, 614), correlation equations were presented for the inhibition of bovine liver and Escherichia coli dihydrofolate reductase (DHFR) by 5-(substituted benzyl)-2,4-diaminopyrimidines. These equations brought out differences in the way these two enzymes interact with substituents, which explain the high selectivity of drugs like trimethoprim. We have tested and further developed these equations in this report. It is of particular interest that our previously published correlation equation for E. coli DHFR accurately predicted the potency of a commercial competitor of trimethoprim (tetroxoprim) now in clinical use. We believe that new and effective competitors for trimethoprim can be designed by means of the two correlation equations.
在我们之前的出版物中（布莱尼，J.M.；迪特里希，S.W.；雷诺兹，M.A.；汉斯克，C.《药物化学杂志》1979年，22卷，614页），给出了5-（取代苄基）-2,4-二氨基嘧啶对牛肝和大肠杆菌二氢叶酸还原酶（DHFR）抑制作用的相关方程。这些方程揭示了这两种酶与取代基相互作用方式的差异，这解释了甲氧苄啶等药物的高选择性。在本报告中，我们对这些方程进行了测试并进一步完善。特别值得关注的是，我们之前发表的关于大肠杆菌DHFR的相关方程准确预测了目前正在临床使用的甲氧苄啶商业竞争药物（四氧普明）的效力。我们相信，可以通过这两个相关方程设计出新型且有效的甲氧苄啶竞争药物。
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