高等学校化学学报

高等学校化学学报 ›› 1988, Vol. 9 ›› Issue (10): 1029.

• 论文 • 上一篇    下一篇

5-取代苯硫基-2,4-二氨基嘧啶类化合物的合成及其抑酶活性的定量构效关系研究

仉文陞1, 李仁利1, 张俊东1, Martin Poe2   

  1. 1. 北京医科大学药学院;
    2. Merek Sharp & Dohme Research Laboratories, USA
  • 收稿日期:1987-06-07 出版日期:1988-10-24 发布日期:1988-10-24
  • 通讯作者: 仉文陞
  • 基金资助:

    中国科学院科学基金

Studies on the Synthesis of 5-(Substituted Phenyl) Thio-2,4- Diaminopyrimidines and Their QSAR of the Inhibition to E. coli DHFR

Zhang Wensheng1, Li Renli1, Zhang Jundong1, Martin Poe2   

  1. 1. Department of Pharmaceutical Sciences, Beijing Medical University, Beijing;
    2. Merck Sharp & Dohme Research Laboratories, U S A
  • Received:1987-06-07 Online:1988-10-24 Published:1988-10-24

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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.coliMB1428DHFR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·coliDHFR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。

关键词: 5-(取代苯硫基)-2, 4-二氨基嘧啶类化合物, QSAR, 二氢叶酸还原酶抑制剂

Abstract: Eight dihydrofolate reductase inhibitors, 5-(X-phenyl) thio-2,4-diamino-pyrimidines (X = 4′-NH2 and its hydrochloride; 4′-Ihydrochloride;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 DHFRhave 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 π3,4,5. MR′is, defined with a maximum value cf 0.79 which means the MRvalues 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.

Key words: Pyrimidine derivatives, QSAR, Dihydrofolate reductase inhibitor

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