Acta Chimica Sinica ›› 2009, Vol. 67 ›› Issue (22): 2592-2596. Previous Articles     Next Articles

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氟喹诺酮C3稠杂环体系的合成及抗肿瘤活性(III): 恩诺沙星均三唑并噻二嗪酮衍生物

胡国强*,a,张忠泉a,王海燕a,毋小魁a,王 新a,杜钢军a,谢松强a,黄文龙b,张惠斌b   

  1. (a河南大学药物研究所 开封 475001) (b中国药科大学新药中心 南京 210009)
  • 投稿日期:2009-04-11 修回日期:2009-05-16 发布日期:2009-07-24
  • 通讯作者: 胡国强 E-mail:hgaxy@sina.com.cn

Synthesis and Antitumor Activity of Fluoroquinolon-3-yl Fused Heterocyclic Systems (III): s-Triazolothiadiazinone Derivatives Derived Enrofloxacin

Hu, Guoqiang*,a,Zhang, Zhongquana,Wang, Haiyana,Wu, Xiaokuia,Wang, Xina Du, Gangjuna,Xie, Songqianga,Huang, Wenlongb,Zhang, Huibinb   

  1. (a Institute of Pharmacy, Henan University, Kaifeng 475001) (b Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
  • Received:2009-04-11 Revised:2009-05-16 Published:2009-07-24

The topoisomerase-based design and development for the shift from an antibacterial to an antitumor agent have been a new strategy in the fluoroquinolone field. To further expand the research of the C-3 fused heterocyclic rings attached to the quinolinone skeleton, the key intermediate of 1-amino-5-mercapto- 1,3,4-triazole (5) derived from the C-3 carboxyl group of enrofloxacin 1 was synthesized, then, the corresponding fused heterocyclic ring, s-triazolo[2,1-b][1,3,4]thiadiazin-3-one (7), was produced by a cyclocondensation of 5 with chloroacetic acid. The further modification for the above fused core 7 by a Perkin reaction with substituted benzaldehydes yielded the title compounds, 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6- fluoro-3-{2-(substituted-benzylidene)-3,4-dihydro-[1,3,4]triazolo[2,1-b][1,3,4]thiadiazin-3-(2H)-one-5- yl)}quinolin-4-(1H)ones (8), respectively. The structures of new compounds synthesized were characterized by elemental analysis and spectral data, and their in vitro anticancer activity against the three cancer cell lines of CHO, HL60 and L1210 was evaluated. The bioactive assay showed that all new compounds, especially the intermediate 6 exhibited a significant antitumor activity with a range of the micromole concentrations for IC50 value. Thus, the C-3 mono or fused heterocycle-based substituted antitumor fluoroquinolones are valuable for further study.

Key words: fluoroquinolone, s-triazole, s-triazolothiadiazinone, anticancer evaluation