5H-哒嗪并[4,5-b]吲哚类新化合物的合成及 抗肿瘤细胞增殖活性

目的 设计并合成5H-哒嗪并4,5-b]吲哚类化合物，评价其体外抗肿瘤细胞增殖活性。方法 以7-溴-1-氯-8-(3-氯丙氧基)-5-环丙基-5H-哒嗪并4,5-b]吲哚为起始原料，经取代、醚化、Mannich 反应、选择性氧化共3步或4步反应合成目标化合物；以吉非替尼(gefitinib)为阳性对照药，采用 MTT 法测定了目标化合物对肿瘤细胞株 Bel-7402 和 HT-1080 的抗增殖活性。结果与结论 合成了13 个化合物，其中12 个是未见文献报道的新化合物，其结构经¹H-NMR、MS 谱确证；8个化合物显示出较好的抗肿瘤细胞增殖活性，其中，化合物4a和5a抗增殖活性突出，分别为吉非替尼的3倍和4倍。

Synthesis and antiproliferative activity of novel 5H-pyridazino[4,5-b]indole derivatives

Aim To design and synthesize 5H-pyridazino4,5-b]indole derivatives and evaluate their in vitro antiproliferative activities.Methods The target compounds were synthesized in 3-4 steps including substitution reaction,etherification,Mannich reaction and selective oxidation starting from 7-bromo-1-chloro-8-（3-chloropropoxy）-5-cyclopropyl-5H-pyridazino4,5-b]indole,and their antiproliferative activities against cancer cell lines,Bel-7402 and HT-1080,were tested by MTT assay.Results and conclusion Thirteen compounds were synthesized,and the structures of twelve new compounds were confirmed by 1H-NMR and MS.Eight compounds showed potent antiproliferative activities,and compounds 4a and 5a displayed promising activities which was three and four times better than gefitinib,respectively.