TYK2抑制剂BMS986202的合成工艺  

Synthesis Processs of TYK2 Inhibitor BMS986202

作　　者：张倩倩 李铭东 党诗涵 李春 李庶心 胡文祥 闵清 ZHANG Qianqian;LI Mingdong;DANG Shihan;LI Chun;LI Shuxin;HU Wenxiang;MIN Qing(College of Pharmacy,Hubei University of Science and Technology,Xianning 437100,China;College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330000,China;Suzhou Longbotai Pharmaceutical Co.,Ltd.,Suzhou 215000,China;Jingdong Xianghu Microwave Chemistry Union Laboratory,Beijing Shenjian Tianjun Medical Science Research Institute,Beijing 101601,China)

机构地区：[1]湖北科技学院药学院,湖北咸宁437100 [2]江西中医药大学药学院,江西南昌330000 [3]苏州隆博泰药业有限公司,江苏苏州215000 [4]北京神剑天军医学科学研究院,京东祥鹄微波化学联合实验室,北京101601

出　　处：《合成化学》2024年第4期332-338,共7页Chinese Journal of Synthetic Chemistry

摘　　要：BMS986202是一种有效的,具有选择性的口服活性TYK2抑制剂,对包括JAK家族在内的激酶具有高度选择性,可用于IL-23驱动的棘皮症、抗CD40诱导的结肠炎和自发性狼疮的治疗,具有良好的开发和应用前景。以1-溴-2-甲氧基-3-硝基苯为起始原料,经还原、偶联、芳基化和酰胺化4步反应得到BMS986202,并对BMS986202的合成路线进行优化,总收率为85%,其结构经^(1)H NMR和MS(ESI)表征。结果表明:该方法步骤简单,反应条件温和,操作方便,具有较好的工业化前景。BMS986202,a potent,selective and orally active TYK2 inhibitor is remarkably selective over other kinases including JAK family members and it can be used for the treatment of IL-23-driven acanthosis,anti-CD40-induced colitis,and spontaneous lupus,which has a good prospect of development and application.The improved synthetic route of BMS986202 has been developed.By using 1-bromo-2-methoxy-3-nitrobenzene as staring material,BMS986202 was obtained through four steps including reduction,coupling,arylation and amidation.The total yield was increased to 85%and the structure of product was characterized by^(1)H NMR and MS(ESI).The results showed that with the advantages of mild reaction condition,simple step,convenient to handle,this route is suitable for the industrial production.

关 键 词：BMS986202 氘可来昔替尼 合成 TYK2抑制剂 JAK抑制剂 工艺改进 SUZUKI偶联反应 

分 类 号：R9[医药卫生—药学]