Chinese Journal of Organic Chemistry >
Synthesis and Biological Evaluation of Pyrimidine Derivatives Containing Hydrazine Structural Unit
Received date: 2019-03-27
Revised date: 2019-05-12
Online published: 2019-06-06
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
He Haifeng , Xia Qin , He Hongwu . Synthesis and Biological Evaluation of Pyrimidine Derivatives Containing Hydrazine Structural Unit[J]. Chinese Journal of Organic Chemistry, 2019 , 39(8) : 2295 -2302 . DOI: 10.6023/cjoc201903064
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