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肠道病毒71型(EV71)是目前我国手足口病的主要致病病原,EV71感染不仅造成轻症病例,还能造成重症和死亡病例,目前尚无有效治疗EV71感染的药物上市.TJAB1099是基于EV71的衣壳蛋白VP1结构设计出的有效抗病毒抑制剂分子,临床前研究证实其具有很好的成药性.主要研究了TJAB1099的有效制备方法.以2-氨基-4-溴吡啶为起始原料,经过6步化学转化,以12%的总收率得到纯度大于99%的抑制剂分子TJAB1099.合成过程中无需硅胶柱纯化操作.该路线经过多批次百克级的起始投料,收率稳定且抑制剂分子杂质含量稳定,完全可以满足其临床前实验所需的抑制剂制备量,并且也为其之后进一步的大规模生产打下基础.
Enterovirus 71 (EV71) is currently the main causative agent of HFMD in China, and EV71 infection not only causes mild cases but also causes severe and fatal cases, so far no effective drug for EV71 infection has been listed. TJAB1099 is based on EV71 capsid protein VP1 structure designed effective antiviral inhibitor molecules, preclinical studies have shown that it has a good drug-induced properties.This paper mainly studies the efficient preparation method of TJAB1099.Starting with 2-amino-4-bromopyridine The raw material, after 6 steps of chemical conversion, obtained the inhibitor molecule TJAB1099 with a purity of more than 99% in a total yield of 12% without silica gel column purification during the course of the synthesis. Stable and stable molecular weight of the inhibitor molecules, can fully meet the preparation of inhibitors required for its preclinical experiments, and also lay the foundation for further large-scale production thereafter.