Design, Synthesis And Antitumor Activity Of 1,3,5-substituted Indazole Derivative

Indazole and its derivatives are important synthetic intermediates and heterocyclic compounds,which have a wide range of biological activities,such as anti-tumor,anti-inflammatory,anti-hypertension,anti-bacterial,etc.,and are common dominant skele-tons in many drug molecules.In this paper,two series of 1,3,5-substituted indazole derivatives were designed and synthesized,including 32 derivatives,17 n-series compounds and 15 AM-series compounds.The structures were confirmed by ¹H NMR,¹³C NMR and HRMS.At the same time,the inhibitory effect of the target compound on human non-small cell lung cancer（A549）,human hepatocellular carcinoma cell（HepG2）,human chronic bone marrow leukemia cell（K562）and human prostate cancer cell（PC-3）was evalu-ated by MTT method.The experimental results showed that the N series target com-pound had certain antitumor activity,and the inhibitory rate of compound N17 on HepG2 cell was 38.85%at the concentration of 10μm.Its inhibitory activity was 30.41%higher than that of gefitinib,and the inhibitory rate of compound N14 on PC-3 cells was 34.62%,which was similar to that of gefitinib on PC-3 cells,which was 35.05%.AM series target compounds are targeted at A549 cells,and the inhibitory effects of compounds AM3 and AM14 on A549 cells are better than those of 5-fluorouracil（IC50is 6.34μM）,so the corresponding IC50 values of compounds AM3 and AM14 are 5.50μM and 5.92μM.Finally,the structure-activity relationship of the target compound AM1-AM15 was analyzed,the 5-substituted indazole derivatives were superior to other substituents in inhibiting the proliferation of cancer cells（A549 cells）,and 1,3,5-trimethoxy substitu-ents were introduced into the benzene ring,5-substituted indazole derivatives showed the strongest anticancer activity.