The Synthesis,biological Evaluation And Theoretical Analysis Of Several Triazolopyrimidine Sulfonamide

Acetolactate synthase?ALS?is one of most identical target enzymes for the herbicide design.As ALS does not exist in human and non-target organisms,it only exists in plants,bacteria,fungi,and algae,it is low toxicity or nontoxic to human and animals.Triazolopyrimidine sulfonamide herbicides are marketed as relatively successful acetolactate synthase inhibitors,which are developed from sulfonylurea herbicides as lead compounds by application of bioisostere method.Penoxsulam is one important triazolopyrimidine sulfonamide herbicides recently developed by Dow.Agro Sciences.It is widely used for weed control in the rice field.Because of its broad weed spectrum of herbicides,high herbicidal activity,high safety,and long-lasting effects,it has been praised as an"Dao Jie"in China.However,as the structure of penoxsulam is complicated and the production cost is high,it is of great significance to design novel triazolopyrimidine sulfonamide with simple structure and high activity.Based on former results of the research group and the structure of triazolopyrimidine sulfonamide,three new triazolopyrimidine sulfonamide compounds?1?N-?4,7-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine?-2-chlorine-4- nitrobenzene sulfonamide?Name:Cl-NO₂?;?2?N-?4,7-Dimethoxy[1,2,4]-triazolo[1,5-c]pyrimidine?-2-methoxycarbonyl-4-nitrobenzenesulfonamide?Name: ME-NO₂?;?3?N-?4,7-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine?-2-ethoxycarbonyl-4-nitrobenzene-sulfonamide?Name:EF-NO₂?were synthesized using the similar synthesis method of penoxsulam.The structure of compounds were verified by using the IR spectrum,¹H-NMR spectrum and elemental analysis.Meanwhile,the herbicidalacivity of pre-and post-emergence treatment against Amaranthus were tested.It was found the compound Cl-NO₂ shows high herbicidal acitivty,the inhibition to Amaranthus is about 95%with application rate of 9.0?g/acre?,and it is nontoxic to rice,but its herbicidal activity is slightly lower than that of penoxsulam.Molecular docking can be used not only to determine the binding conformation of the ligand within the target binding pocket,but also to predict the interaction energy between the target and the ligand.In this paper,two docking softwares,AutoDock 4 and AutoDock Vina,were used to analyze the binding conformations of three synthetic compounds and the target ALS enzyme and their interactions between ligands and amino acid residues of the binding pocket.The binding modes of triazolopyrimidine sulfonamide and sulfonylurea compounds with the target ALS enzyme were also compared.The results is helpful for the further development of highly active triazolopyrimidine sulfonamide compounds in the future.