【摘要】 本文报道8个5-(取代苯硫基)-2,4-二氨基嘧啶类化合物的合成,测定了对E.coliMB1428 DHFR的抑制活性。对16个本类化合物进行Hansch分析表明,本类化合物对E·coli DHFR的抑制作用与3′,4′,5′-位取代基限制数值的立体参数呈线性关系,与取代基的疏水性参数呈双线性关系。更多还原

【Abstract】 Eight dihydrofolate reductase inhibitors, 5-(X-phenyl) thio-2,4-diamino-pyrimidines (X = 4/-NH2 and its hydrochloride; 4’-I hydrochloride;4/-NHCOCH3; 4’-OH, 4’,-NNSCH3; 3’ ,5’- (Br) 2,4’ -NH2 hydrochloride, 4’-OCH2CH3; 4’-OCH2CH2CH3), have been synthesized from 5-(4’ -nitrophenyl) thio-2,4-diamino pyrimidine. Their inhibitory activities to E.coli MB 1428 DHFR have been tested. All sixteen thiophenyl pyrimidines (eight of them were reported previously) have been correlated with Hansch analyses. The correlation equation shows that their inhibitory activities are linearly correlated with MR3,4,5 and bilinearly correlated with π.3,4,5. MR’ is, defined with a maximum value cf 0.79 which means the MR values of substitvents have to te trurcaled at the value of 0.79 when the substituent is larger than methoxy group, similar to the definition in the correlation of benzylpyrimidines.更多还原