Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (8): 2295-2302.DOI: 10.6023/cjoc201903064 Previous Articles     Next Articles

Special Issue: 陈茹玉先生诞辰100周年

Articles

含腙结构单元的氨基嘧啶衍生物的合成与生物活性研究

何海峰b, 夏芹a, 贺红武a   

  1. a 华中师范大学化学学院 农药与化学生物学教育部重点实验室 武汉 430079;
    b 江西科技师范大学化学化工学院 南昌 330046
  • 收稿日期:2019-03-27 修回日期:2019-05-12 出版日期:2019-08-25 发布日期:2019-06-06
  • 通讯作者: 贺红武 E-mail:he1208@mail.ccnu.edu.cn
  • 基金资助:

    国家自然科学基金(Nos.21877047,21867011)、江西省教育科技厅基金(No.GJJ170672)资助项目.

Synthesis and Biological Evaluation of Pyrimidine Derivatives Containing Hydrazine Structural Unit

He Haifengb, Xia Qina, He Hongwua   

  1. a Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079;
    b School of Chemistry and Chemical Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013
  • Received:2019-03-27 Revised:2019-05-12 Online:2019-08-25 Published:2019-06-06
  • Contact: 10.6023/cjoc201903064 E-mail:he1208@mail.ccnu.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21877047, 21867011) and the Project of Science Fund of Jiangxi Education Office (No. GJJ170672).

Pyruvate dehydrogenase multienzyme complex (PDHc) is a key enzyme linking glycolysis and the tricarboxylic acid cycle. Currently, there is no fungicide targeting pyruvate decarboxylase (PDHc-E1), the purpose of this study was to obtain compounds with bactericidal activity by designing inhibitors against PDHc-E1. On the basis of lead compound L, fourteen novel aminopyrimidine derivatives I were designed and synthesized by the condensation reaction of hydrazine and aldehydes as potential PDHc-E1 inhibitors. The most effective 5-((2-(4-bromophenyl)hydrazono)methyl)-2-methylpyridin-4-amine (I-6) with good E. coli PDHc-E1 enzyme inhibitory activity (IC50=26.45 μmol/L) exhibited most powerful inhibitory potency against Cercospora arachidicola Hori (EC50 14.11 μg/mL) and Physalospora piricola Nose (EC50 0.64 μg/mL). Therefore it could obtain the compound with antifungal activity against microorganism PDHc-E1 enzyme by modifying the bridged linkage in lead structure 2-methyl-4-amino-pyrimidine derivatives L.

Key words: PDHc-E1, fungicide, lead compound, 2-methyl-4-amino-pyrimidine derivatives