新型吲唑类化合物的合成及其抗肿瘤活性

摘要

2-Fluoro-6-morpholinobenzonitrile(1) was prepared by reaction of 2,6-difluorobenzonitrile with morpholine.4-Morpholino-1H-indazol-3-amine(2) was synthesized by cyclization of 1 with hydra-zine.2 was coupled with various carboxylic acids to afford eight novel indazole derivatives(4a~4h). The structures were characterized by 1H NMR, IR and HR-ESI-MS.The antitumor activities were in-vestigated.The results showed that 4-(4-methylpiperazin-1-yl)-N-(4-morpholino-1H-indazol-3-yl)-4-oxobutanamide(4a) exhibited potent antitumor activities against K-562, SMMC7721 and T-47D tumor cell lines with IC50 of 0.056 μmol· L-1 , 0.062 μmol· L-1 and 0.086 μmol· L-1 , respectively.%以2,6-二氟苯腈与吗啉反应制得2-氟-6-吗啉-苯腈(1);1与水合肼在N-甲基吡咯烷酮中通过环合反应制得3-氨基-4-吗啉-1H-吲唑(2);2与不同羧酸经缩合反应合成了8个新型吲唑类化合物(4a~4h),其结构经1 H NMR,IR和HR-ESI-MS表征.抗肿瘤活性测试结果表明:3,4,5-三甲氧基-氮-(4-吗啉-1H吲唑-3-基)苯甲酰胺(4a)的抗肿瘤活性最好,对K-562,SMMC7721和T-47D肿瘤细胞有明显抑制作用,IC50分别为0.056μmol·L-1,0.062μmol·L-1和0.078μmol·L-1.