Design, synthesis and SAR study of novel sulfonylurea derivatives containing arylpyrimidine moieties as potential anti-phytopathogenic fungal agents  

作　　者：Wei Chen Yuxin Li Yunyun Zhou Yi Ma Zhengming Li 

机构地区：[1]School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China [2]State Key Laboratory of Elemento-Organic Chemistry,Nankai University,Tianjin 300071,China [3]State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Fudan University,Shanghai 200433,China

出　　处：《Chinese Chemical Letters》2019年第12期2160-2162,共3页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.21702173,21502229);Fundamental Research Funds for the Central Universities(No.2682016CX104);Miaozi Project of Scientific and Technological Innovation of Sichuan Province(No.2018090)

摘　　要：Acetohydroxyacid synthase(AHAS) was considered as a promising target for antifungal agents.Herein,three series of novel sulfonylureas(SUs) 9-11 containing aromatic-substituted pyrimidines were designed and synthesized according to pharmacophore-combination and bioisosterism strategy.The in vitro fungicidal activities against ten phytopathogenic fungi indicated that most of the title compounds exhibited broad-spectrum and excellent fungicidal activities.Based on the preliminary fungicidal activities,a CoMFA model was constructed and the 3 D-QSAR analysis indicated that either a bulky group around the 5-position of the pyrimidine ring or electropositive group around the 2-position of the benzene ring would be favour to fungicidal activities.In order to study interaction mechanism,10 k was automatically docked into yeast AHAS and it further indicated that bearing bulky groups-aryl at the pyrimidine ring was critical to enhance antifungal activities.It revealed that the antifungal activity of derivatives 9-11 probably results from the inhibition of fungal AHAS.Thus,the present results strongly showed that SUs should be considered as lead compounds or model molecules to develop novel antiphyt o pathogenic fungal agents.Acetohydroxyacid synthase(AHAS) was considered as a promising target for antifungal agents.Herein,three series of novel sulfonylureas(SUs) 9-11 containing aromatic-substituted pyrimidines were designed and synthesized according to pharmacophore-combination and bioisosterism strategy.The in vitro fungicidal activities against ten phytopathogenic fungi indicated that most of the title compounds exhibited broad-spectrum and excellent fungicidal activities.Based on the preliminary fungicidal activities,a CoMFA model was constructed and the 3 D-QSAR analysis indicated that either a bulky group around the 5-position of the pyrimidine ring or electropositive group around the 2-position of the benzene ring would be favour to fungicidal activities.In order to study interaction mechanism,10 k was automatically docked into yeast AHAS and it further indicated that bearing bulky groups-aryl at the pyrimidine ring was critical to enhance antifungal activities.It revealed that the antifungal activity of derivatives 9-11 probably results from the inhibition of fungal AHAS.Thus,the present results strongly showed that SUs should be considered as lead compounds or model molecules to develop novel antiphyt o pathogenic fungal agents.

关 键 词：SULFONYLUREA Phytopathogenic fungi Antifungal activity Substituted pyrimidine 3D-QASR 

分 类 号：TQ455[化学工程—农药化工]