Design, Synthesis And Biological Activity Of Novel Isoxazolo[5,4-d]pyrimidin-4(5H)-one (Or Isoxazolo[5,4-d][1,2,3]Triazin-4(3H)-one) Derivatives

The protoporphyrinogen oxidase (PPO, E.C.1.3.3.4) inhibitor is one of the rapid development commercial herbicides in recent years. Generally, commercial cyclic imides possess the following structural features:(i) a heterocycle structure with one or more nitrogen atoms;(ii) a polysubstitutedbenzene ring that links with the nitrogen atom of the heterocycle ring. To discover new PPO inhibitors, we synthesized 33 new isoxazolo[5,4-d]pyrimidin-4(5H)-one and isoxazolo[5,4-d][1,2,3]triazin-4(3H)-one derivatives based on the structure-activity relationship of known PPO inhibitors through 10 steps from starting materials. Mainly, the effect to biological activity of groups at 3rd position in isoxazole ring and at 4th and 5th position of polysubstituted benzene ring was studied. All of the new compounds were characterized by HRMS and 1H NMR and some of them were further confirmed by IR and X-ray Diffraction. In addition, the mechanism of annulation was speculated via the characterization of the intermediate, methyl N-4-phenylcarbamoyl-3-methylisoxazol-5-ylacetimidate.According to herbicidal-activity results, most of the title compounds showed good herbicidal activity and some of them expressed high selectivity in herbicidal activity. At the application rate of 12.5 g/acre, B5 can completely inhibit Amaranthus retroflexus L. In addition, the title compounds possessed certain anti-liver-cancer activity, for example, compound B14 showed 71.1% inhibition against MTT at the application rate of lmmol/L, which provided a guide to further design of highly active compounds.