Synthesis And Biological Acticity Of The Inhibitors Of N-nitroaniline Based On The Structure Of Target Enzyme

The sulfonylurea herbicides are broad-spectrum herbicides of high efficient, low toxicity, high selectivity. Its target enzyme is Acetolactate Synthase(ALS). In recent years,with slather of ALS inhibitors, the resistance of weeds increased. At the same time, the speed of resistant weeds appeared faster and faster, the types appeared more and more.Therefore, the new herbicides are developed immediately.Our group have explored for a long period previously, we designed and synthesized a variety of new compounds containing N-nitro-aniline. The studies have shown that these compounds exhibit good herbicidal and fungicidal activities. This paper is that design and synthesis two types of new compounds containing N-nitro-aniline by the methods of combine active substructures stitching with computer aided drug design based on our previous study. Then we test the biological activity of synthetic compound. The specific study is as follows:Firstly, design the structure of compounds: we design two skeletal structure of compounds that N-nitro-N-(2, 4, 6-trichlorophenyl)acrylamide(compounds of class A)and aryl aldehyde(ketone) oxime ether containing N-nitroaniline(compounds of class B)based on the features of the ALS target activity cavity by small molecule active substructures stitching with computer aided drug design. These are for the next research.Secondly, synthesize compounds: 2, 4, 6-trichloroaniline as the starting material was nitrified. We could get N-nitro-2, 4, 6-trichloroaniline. The ester was formed by the reaction of substituted phenol and ethyl propionate, then hydrolysis, acylate, we can get acyl chloride. We got 5 compounds of class A by the reaction between acyl chloride and N-nitro-2, 4, 6 Trichloroaniline. We got oxime by synthesis aldehydes(ketones) and hydroxylamine hydrochloride. The oxime reacted with 1, 2-dibromoethane for oxime ethers, then oxime ether and N-nitro-2, 4, 6-trichloroaniline occured the nucleophilic substitution. we could get 24 compounds of class B. We analyzed the physical and chemical properties identified by IR and1 H NMR for 29 new target compounds.Lastly, test the bioactivity of target compound and analyze the result: we test inhibitory activities on the levels of ALS enzyme because of the structure of the compounds was designed based on the features of the ALS target activity cavity. Theresult showed the compounds of Class A had certain potential activity. The IC50 value of compound A-2 reached 20 ppm. Whereas Class B had no activity to ALS enzyme. We analyzed cause of low activities by theoretical simulation. It maybe caused by strong conjugate of compound structure or long chain.Overall, the research in this paper laid some initial foundation for the study of the herbicides of new novel N-nitro-aniline.