Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (9): 2361-2368.DOI: 10.6023/cjoc201704002 Previous Articles     Next Articles



贺万丽a,c, 赵杨杨a,c, 毛永红a, 赵佩佩a, 汪颖a,c, 蔡岩a,b   

  1. a 天津国际生物医药联合研究院 天津 300457;
    b 南开大学药物化学生物学国家重点实验室 天津 300071;
    c 南开大学药学院 天津 300071
  • 收稿日期:2017-04-01 修回日期:2017-04-26 发布日期:2017-05-10
  • 通讯作者: 赵佩佩, 汪颖, 蔡岩;;
  • 基金资助:


Practical Synthesis of TJAB1099:An Effective Anti EV71 Inhibitor

He Wanlia,c, Zhao Yangyanga,c, Mao Yonghonga, Zhao Peipeia, Wang Yinga,c, Cai Yana,b   

  1. a Tianjin International Joint Academy of Biomedicine, Tianjin 300457;
    b State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071;
    c College of Pharmacy, Nankai University, Tianjin 300071
  • Received:2017-04-01 Revised:2017-04-26 Published:2017-05-10
  • Contact: 10.6023/cjoc201704002;;
  • Supported by:

    Project supported by the State Key Laboratory of Medicinal Chemical Biology Open Fund (Nankai University) (No. 201602003), and the Science and Technology Planning Project of Tianjin City (Nos. 13ZCZDSY04200, 14ZCZDSY00039).

Enterovirus 71 (EV71) is the main pathogen caused Human Hand, Foot and Mouth Disease (HFMD) in China. It not only caused mild case, but also serious case. However, no effective commercialize drugs for the treatment of HFMD were available nowadays. TJAB1099 is an effective EV71 inhibitor which was designed based on the capsid protein VP1 of EV71. The preclinical study has revealed that it owns excellent druggability. Here an practical synthesis of TJAB1099, initiated with 2-amino-4-bromide pyridine is reported. The total synthetic steps are six and its total yield is 12%. The purity of TJAB1099 is more than 99%, and silic gel chromatography is not required in the whole process. This synthetic method has been examined by hectogram level starting feeding for several times, and the total yield and the content of impurities are stable. This method could meet the need of the inhibitor amount for the preclinical study, and it could lay the foundation of further large scale synthesis.

Key words: enterovirus 71, inhibitor, synthetic method