Synthesis,Structure and Biological Activity of 2-[2-(4-Fluorobenzylidene)hydrazinyl]-4-(1-methyl-1H-indol-3-yl)thieno[3,2-d]pyrimidine

The title compound 2-[2-(4-fluorobenzylidene)hydrazinyl]-4-(1-methyl-1 H-indol-3-yl)thieno[3,2-d] pyrimidine(8) was synthesized by the condensation of 4-fluorobenzaldehyde(7) with 2-hydrazinyl-4-(1-methyl-1 H-indol-3-yl)thieno[3,2-d]pyrimidine(6). This intermediate was prepared from methyl 3-aminothiophene-2-carboxylate(1) by the condensation with urea, chlorination with phosphorus oxychloride and then condensation with hydrazine hydrate. The crystal of 8 belongs to monoclinic system, space group P21/c with a = 14.0453(18), b = 17.436(2), c = 18.0982(17) ? and β = 122.969(7)°. In addition, 8 possesses marked inhibition against the proliferation of human colon cancer cell line HT-29(IC50 = 6.09 μM) and human gastric cancer cell line MKN45(IC50 = 3.04 μM), displaying promising anticancer activity.     

新型吲唑-查尔酮杂合物的合成及抗肿瘤活性

设计并合成了一系列新型含查尔酮-吲唑杂合衍生物,并对其体外肿瘤活性进行初步研究。 先以2,6-二氟苯腈和吗啉为起始原料,经过取代和环合两步反应合成4-吗啉-3-氨基-1H-吲唑。 4-吗啉-3-氨基-1H-吲唑与含羧基的查尔酮中间体与经过酰胺化反应制备了9个新型含查尔酮-吲唑杂合衍生物,其结构经傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)、质谱(MS)和元素分析确证。 采用MTT法,以索拉菲尼为阳性对照药,以人胃癌细胞株(MKN45)和人肺癌细胞株(A549)为测试细胞株对目标化合物进行抗肿瘤活性评价。 结果表明,大部分目标化合物显示了较好的抗肿瘤活性,其中化合物4a和4d活性较好,其抑制人胃癌细胞株MKN45的IC₅₀分别为2.65和3.55 μmol/L,均优于阳性对照药索拉菲尼(IC₅₀=4.69 μmol/L)。