Design,Synthesis,Antifungal,Structure-Activity Relationshiop Of Novel Pyrazoles SDHIs

Heterocyclic compounds,especially nitrogen-containing heterocycles,has been a hot spot in many fields.Pyrazole,as an important kind of nitrogen heterocycle,have been widely used in medicine and pesticides.It is usually used as fungicides in agricultural field.For example,succinate dehydrogenase inhibitors including many pyrazole compounds with the advantages of high efficiency and low toxicity and environmental safety,plays an important role in agriculture.This paper is based on the structure-activity relationship of the existing structure of pyrazole fungicides and succinate dehydrogenase inhibitors.And the study is based on methods of bioisostere and active connection,through a mode of introduction and transformation of heterocyclic amide bond.The paper is designed and sythesis of 149 novel pyrazole compounds,the structure of title products were confirmed by at least two ways in 1H NMR,13 C NMR,IR,HRMS and X-diffraction.The fungicidal activity of title products was tested by the method of mycelium growth rate or pot experiment(FusaHum graminearum Sehw,Phytophthora infestans(Mont.)de Bary,Phytophthora capsici Leonian,Sclerotinia sclerotiorum(Lib.)de Bary,Thanatephoruscucumeris,Alternariasolani,Botryosphaeria dothidea,Corynespora mazei,Pseudomonas syringae pv.lachrymans,Botrytis cinerea,Fusarium oxysporum).The results indicated that most of the compounds have certain antifungal activity.Among them,the acyl urea compounds(D1,D3,D7,D8,D9,F1,F2,F3,F5,F7)exhibited the good activity(80%~94%)at 10 ppm,which is higher than the that of control Boscalid or Fluxapyroxad.And the single amide compounds(K14?K15)also exhibited better activity(EC50 approximate 2ppm).Docking studies was done based on the crystal structure and the eymeze SDH.that the results indicated that there are four hydrogen bonds and ?-? interaction between the active compounds and SDH.