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微波辅助合成玛利多米德构建块,用于快速的PROTAC和分子开发

Diaaeldin I Abdallah^1,2, Johan Israelian^1,2, Lina S Hasan¹

¹Department of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada. patrick.gunning@utoronto.ca.

Chemical communications (Cambridge, England)

|March 10, 2025

概括

微波辅助合成 (MAS) 加快了针对蛋白质降解 (TPD) 药物的玛利多米德构建块的产生. 这种优化的方法显著减少了反应时间,提高了产量,加速了药物发现.

科学领域:

药用化学医学化学
药物发现药物发现药物发现
有机合成有机合成

背景情况:

向蛋白质降解 (TPD) 是药物发现的一个快速发展的领域.
目前的PROTAC合成方法,特别是链接器安装,往往是缓慢和复杂的,阻碍了开发.
利多米德衍生物用于TPD的合成需要高效和可扩展的化学过程.

研究的目的:

使用微波辅助合成 (MAS) 优化玛利多米德构建基的合成.
证明MAS在加速PROTACs和分子合物的发展中的实用性.
为了提高产量和减少TPD药物发现中关键中间体的反应时间.

主要方法:

优化微波辅助合成 (MAS) 用于利多米德构建块.
马斯与传统加热方法 (油浴) 的比较.
合成ARV-110 PROTAC以展示该方法的适用性.

主要成果:

在使用MAS时,仅在15分钟内就获得了高产量的玛利多米德构建块.
与传统方法相比,在克拉尺度上至少提高了14%的产量.
消除了对净化步骤的需求,简化了合成过程.
成功合成了ARV-110 PROTAC,证明了该方法的实际效用.

结论:

微波辅助合成 (MAS) 提供了一种显著更快,更有效的方法来生产波马利多米德构件.
MAS简化了PROTACs和分子合物的合成,加速了药物发现计划.
这种优化的合成策略克服了TPD药物开发中的关键瓶.

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