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