5-取代苄基-2,4-二氨基嘧啶制菌作用的构效关系

STRUCTURE-ACTIVITY RELATIONSHIPS OF 5-(SU3-STITUTED BENZYL)-2,4-DIAMINO PYRIMIDLNES

为了肯定以前研究结果的可靠性,合成了9个新的5-取代苄基-2,4-二氨基嘧啶类化合物(Ⅰ),并以大肠杆菌(1515)测定了它们的制菌活性。应用Hansch途径研究了31个化合物的定量构效关系:制菌作用与苯环上3,4,5-位取代基的立体参数之和(MR_(3,4,5))呈抛物线关系,取代基的电性参数(σ_R^-)可以改善相关关系。

For the comfirmation of oar previous studies, nine new 5-(suhstHuted benzyl)-2, 4-diaiaine pyr-imidines (Ⅰ) are synthesized (synthetic procedures of seven of them will be published separately). E. coli (1515) bacteria is used in testing their bacterial-static activity. The results show that compounds with same sabsihaents but on different position cf benzene ting, or with different substituents having identical steric parameter possess very close bacterial-static activities. Quantitative structure-activity correlation analysis studies utilizing Hansch approach show that activities are parabolically correlated with the sum of steric parameter (MR3,4,5) of 3-, 4-, and 5-subsntiuents as benzene ring (u = 0.848, s=0.280, F2,25=31,96). Correlation can be improved by the electronic parameter of subsstituests (σR-) (r=0.880, s=0.257, F1,24=15.37), Kubinyi bilinear model can not significantly improve the correla-tions. The correlation result of this study is quite similar with that of our previous work.