Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

doi:10.6023/cjoc201407042

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (12): 2505-2510.DOI: 10.6023/cjoc201407042 Previous Articles Next Articles

ARTICLE

吡唑环桥连简约型长春碱类似物的设计合成

国翠平^a, 彭群龙^a, 潘龙^a, 张冬梅^a,b, 陈河如^a,b

a. 暨南大学药学院中药及天然药物研究所广州 510632;
b. 广东省中药药效物质基础及创新药物研究重点实验室广州 510632

收稿日期:2014-07-29 修回日期:2014-08-27 发布日期:2014-08-29
通讯作者: 陈河如 E-mail:thrchen@jnu.edu.cn
基金资助:
国家自然科学基金(No.81172982)资助项目.

Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

Guo Cuiping^a, Peng Qunlong^a, Pan Long^a, Zhang Dongmei^a,b, Chen Heru^a,b

a. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
b. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Guangzhou 510632

Received:2014-07-29 Revised:2014-08-27 Published:2014-08-29
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81172982).

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 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 μmol/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.

Key words: pharmacophore similarity, simplified design, vinca alkaloids analogues, antitumor, drug synthesis

Cite this article

Guo Cuiping, Peng Qunlong, Pan Long, Zhang Dongmei, Chen Heru. Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues[J]. Chin. J. Org. Chem., 2014, 34(12): 2505-2510.

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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

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