Design, Synthesis And Nematicidal Activity Of Novel Imidazo[1,2-a]pyridine-containing Sulfone Derivatives

Fluazaindolizine,a new type of high-efficiency and environment-friendly nematicide containing an imidazo[1,2-a]pyridine moiety,was developed by Du Pont,which has attracted the attention of nematode researchers to the structure of imidazo[1,2-a]pyridine.Search for new nematicides from imidazo[1,2-a]pyridine derivatives have good research value and application prospects.In previous research of our group,we found that sulfone derivatives showed good nematicidal activities.To find new nematicides with high efficiency,the sulfone group was introduced into the imidazo[1,2-a]pyridine structure.Subsequently,a series of new sulfone derivatives containing an imidazole[1,2-a]pyridine moiety were designed and synthesized.Then their nematicidal activities were evaluated.The conclusions were as follows:1.Designed and synthesized 28 novel sulfone compounds containing an imidazo[1,2-a]pyridine.Their structures were characterized by Nuclear Magnetic Resonance and HRMS.2.We used Aphelenchoides besseyi(A.besseyi)and Caenorhabditis elegans(C.elegans)as research objects to test their nematicidal activities.The test results showed that some of the target compounds had excellent nematicidal activities against A.besseyi and C.elegans.Compound 3 had good activity against A.besseyi,with the LC₅₀ value of 27.3 mg/L in vitro.In addition,compound 27 had good nematicidal activity against A.besseyi and C.elegans,with the LC₅₀ value of 35.9 and 5.7 mg/L,respectively,which were better than those of fosthiazate(45.4 and 77.2 mg/L).3.The nematodes treated by compound 27 and fosthiazate were found to show similar symptoms of poisoning.Therefore,compound 27 and fosthiazate might have the same target.We simulated the protein structure of acetylcholinesterase(AChE)of C.elegans.Molecular docking showed that compound 27 had a good binding mode and binding energy with AChE.The binding free energy of compound 27 to AChE was-47.9 kcal/mol,which was superior to that of fosthiazate(-33.6 kcal/mol).This was consistent with the results of the previous nematicidal activity test.The enzyme activity assay results showed that compound 27 could significantly inhibit the AChE activity of C.elegans with an inhibition rate of 71.1%.Therefore,it was speculated that AChE might be a potential target of compound 27 on nematodes.