TYK2抑制剂BMS986202的合成工艺
Synthesis Processs of TYK2 Inhibitor BMS986202
张倩倩 1李铭东 2党诗涵 3李春 4李庶心 5胡文祥 6闵清1
作者信息
- 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. 湖北科技学院 药学院,湖北 咸宁 437100;苏州隆博泰药业有限公司,江苏 苏州 215000
- 4. 江西中医药大学 药学院,江西 南昌 330000;苏州隆博泰药业有限公司,江苏 苏州 215000
- 5. 苏州隆博泰药业有限公司,江苏 苏州 215000
- 6. 湖北科技学院 药学院,湖北 咸宁 437100;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
- 折叠
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1H 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.
Abstract
BMS986202,a potent,selective and orally active TYK2 inhibitor is remarkably selective o-ver 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 develop-ment 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 in-cluding reduction,coupling,arylation and amidation.The total yield was increased to 85％and the structure of product was characterized by 1H NMR and MS(ESI).The results showed that with the ad-vantages of mild reaction condition,simple step,convenient to handle,this route is suitable for the in-dustrial 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Key words
BMS986202/deucravacitinib/synthesis/TYK2 inhibitor/JAK inhibitor/process im-provement/Suzuki coupling reaction引用本文复制引用
出版年
2024
NETL
NSTL
万方数据