吡唑环桥连简约型长春碱类似物的设计合成

Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

利用焦磷酰氯(P2O3Cl4)和DMF为Vilsmeier-Haack试剂,与2,3,3-三甲基-3H-吲哚反应生成二甲酰化中间体化合物,再与肼衍生物反应生成系列吡唑环桥连简约型长春碱类似物2a^2m.目标化合物的结构均经1H NMR,13C NMR和HRMS确证.初步的抗肿瘤活性数据表明,在50μmol/L的浓度下,大部分目标化合物对人乳腺癌细胞株(MCF-7)(estrogen-positive)和人肝癌细胞株(Hep G2)具有一定的抗肿瘤活性,其中2f和2j抗肿瘤作用较强,它们对MCF-7细胞株的存活率分别为28.0%和21.4%;而对Hep G2细胞株的存活率分别为31.6%和34.0%.

A series of pyrazol-brigded simplified vinblastine analogues 2a^2m have been synthesized by the reaction of hydrazine derivatives with diformyl intermediates, which were prepared from 2,3,3-trimethyl-3H-indoles using P2O3Cl4/DMF as Vilsmeier-Haack reagent. All the target compounds have been identified by 1H NMR, 13C NMR and HRMS. The prelimi-nary results of anticancer tests indicated that most of the compounds exhibit certain extent of anticancer activity against both MCF-7 （estrogen-positive） and HepG2 cell lines at the concentration of 50μmol/L, respectively. 2f and 2j are the two best active compounds, where their cell viabilities against MCF-7 cell line are 28.0% and 21.4%, respectively; while against HepG2 cell line, 31.6%and 34.0%, respectively.