Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

作者：Guo Cuiping^*; Peng Qunlong; Pan Long; Zhang Dongmei; Chen Heru

来源：Chinese Journal of Organic Chemistry, 2014, 34(12): 2505-2510.

DOI：10.6023/cjoc201407042

• pharmacophore similarity
• simplified design
• vinca alkaloids analogues
• antitumor
• drug synthesis

A series of pyrazol-brigded simplified vinblastine analogues 2a similar to 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 H-1 NMR, C-13 NMR and HRMS. The preliminary 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 50 mu mol/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.

• 出版日期2014-12
• 单位暨南大学