目的 合成具有抗腫瘤活性的異噁唑類化合物。方法 采用回流、氮?dú)獗Ｗo(hù)等條件，以中間體N-[[3-[3-氟-4-(1-哌嗪基)苯基]-4,5-二氫-5-異噁唑]甲基]乙酰胺的哌嗪基對(duì)位進(jìn)行不同基團(tuán)取代，合成異噁唑系列衍生物，并檢測(cè)所得化合物的抗腫瘤活性。通過分子對(duì)接方法考察了合成化合物與Hsp90蛋白酶結(jié)合的模式。結(jié)果 12個(gè)新化合物的結(jié)構(gòu)經(jīng)¹H-NMR確證。有6個(gè)化合物的腫瘤抑制率＞30%，根據(jù)分子對(duì)接結(jié)合模式找出了取代基的結(jié)構(gòu)改造方向。結(jié)論 合成的部分化合物具有抑制腫瘤的活性。

Objective To synthetize the isoxazole compounds with antitumor activity. Methods The isoxazole derivatives were synthesized under the conditions of backflow and nitrogen protection. At the same time, the antitumor activities were tested. The interaction mode between synthetical compounds and Hsp90 protein was investigated by the molecular docking method. Results A total of 12 new compounds were obtained, and their structures were elucidated by ₁H-NMR technique. There were 6 compounds with tumor inhibitory rate exceeded 30%. A way of modifying substituent structure was shown on the basis of molecular docking model. Conclusion Some of the new compounds have antitumor activities.