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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
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通过液相合成构建PROTAC图书馆,并通过疏水标签使其成为可能
Yifeng Zhou1,2, Wei He3, Zehui Zhou1,2
1Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Organic letters
|February 12, 2026
概括
我们开发了一种新的疏水标签辅助液相合成 (LPS) 技术,用于创建蛋白质解析向金马体 (PROTACs). 这种方法简化了净化,并导致发现了一种具有强烈抗增殖作用的强效雄激素受体 (AR) PROTAC.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药物发现 药物发现 药物发现
背景情况:
- 化向化体 (PROTACs) 是一种新兴的治疗方式.
- 多种PROTAC库的高效合成对于药物发现至关重要.
研究的目的:
- 为 PROTAC 开发制定一种新的,精简的合成战略.
- 构建针对雄激素受体 (AR) 的多种图书馆.
主要方法:
- 使用了疏水标签辅助液相合成 (LPS).
- 通过沉来实现净化,避免了列色谱.
- 合成了各种链接器和AR准的PROTAC库.
主要成果:
- 总共合成了26种PROTACs.
- 化合物25在亚纳米级DC50和Dmax方面表现出高强度.
- 对25号化合物观察到显著的抗增殖活性.
结论:
- 开发的疏水标签辅助LPS是PROTAC合成的有效策略.
- 这种方法有助于快速生成多种不同的 PROTAC 库.
- 化合物25代表了一个非常强大的AR向PROTAC候选者.
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