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设计合成了一系列新型的吲哚-嘧啶联芳类化合物,并评估了它们对组蛋白去甲基化酶(LSD1)的抑制活性和5种肿瘤细胞系(MGC-803,PC-3,EC-109,PC-12和MCF-7)的抗增殖活性.探讨了22个新型吲哚-嘧啶联芳类骨架衍生物的主要构效关系.在这些化合物中,1-(4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)哌嗪-1-基)-2-((3,4,5-三甲氧基苯基)氨基)乙-1-酮(6i)展示出了潜在的LSD1抑制活性(IC50=1.03 μmol/L),而1-(4-(4-(1-甲基-1H-吲哚-3-基)嘧啶-2-基)哌嗪-1-基)-2-(间甲苯胺)乙-1-酮(6c),2-((4-丁基苯基)氨基)-1-(4-(4-(1-甲基-1H-吲味-3-基)嘧啶-2-基)哌嗪-1-基)乙-1-酮(6f)和2-((3-氟苯基)氨基)-1-(4-(4-(1-甲基-1H-吲味-3-基)嘧啶-2-基)哌嗪-1-基)乙-1-酮(6k)对PC-3细胞显示出潜在的抗肿瘤活性.其中活性最强的化合物6k的对PC-3细胞系IC50值为2.75 μmol/L,可作为生物活性片段和开发更有效抗肿瘤药物的靶点化合物.“,”A series of novel indole-pyrimidine biaryl derivatives were designed,synthesized and evaluated for inhibitory activity against Lysine Specific Demethylase 1(LSD1)and antiproliferative activity against five selected cancer cell lines(MGC-803,PC-3,EC-109,PC-12 and MCF-7).The priliminary structure-activity relationship(SAR)for this indole-pyrimidine biaryl scaffold was explored with evaluation of 22 variants of the structural class.Among these analogues,compound 1-(4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)piperazin-1-yl)-2-((3,4,5-trimethoxyphenyl)amino)ethan-1-one(6i)exhibited the potential inhibitory activity against LSD1(IC50=1.03 pmol/L),compounds 1-(4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)piperazin-1-yl)-2-(m-tolylamino)ethan-1-one(6c),2-((4-butylphenyl)amino)-1-(4-(4-(1-methyl-1H-indoi-3-yl)pyrimidin-2-yl)piperazin-1-yl)ethan-1-one(6f)and 2-((3-fluorophenyl)amino)-1-(4-(4-(1-methyl-1H-indol-3-yl)pyri-midin-2-yl)piperazin-1-yl)ethan-1-one(6k)showed the potential inhibitory activity aginst PC-3 cells.Especially,compound 6k exhibited the best antitumor activity(IC50=2.75 pmol/L),which was served as bioactive fragment and hit compound for de-veloping more potent antitumor agents.