基于平行Groebke-Blackburn-Bienaymé反应生成数百万的化学空间
Evgen V Govor1,2, Vasyl Naumchyk1,2, Ihor Nestorak1,3
1Enamine Ltd., Winston Churchill Street 78, Kyїv 02094, Ukraine.
Beilstein journal of organic chemistry
|July 30, 2024
概括
格罗布克-布莱克本-比纳米反应有效地产生了巨大的新型化学空间. 这项研究证明了超过2.71亿种独特的异环化合物的可扩展合成,其中许多显示了现有的生物活性.
科学领域:
- 有机合成 有机合成
- 药品化学 药品化学 是一个
- 化学生物学是化学生物学.
背景情况:
- 格鲁布克-布莱克本-比纳米反应是一种合成化异环的多元组分反应.
- 探索大型,多样化的化学空间对于药物发现至关重要.
- 需要可扩展和高效的合成方法来获得新的化学实体.
研究的目的:
- 评估Groebke-Blackburn-Bienaymé并行反应,以产生一个大型的,化学上可访问的化学空间.
- 在这个反应中比较Sc ((OTf) 3) 和TsOH催化剂的有效性.
- 确定优化合成过程的范围和局限性.
主要方法:
- 通过Groebke-Blackburn-Bienaymé反应,并行合成一个拥有790个成员的图书馆.
- 反应条件的优化和催化剂选择 (Sc(OTf) 3与TsOH).
- 对合成图书馆的多样性进行分析,并与现有的复合藏品进行比较.
主要成果:
- 该Sc(OTf) 3催化协议显示出卓越的性能和更广泛的应用.
- 模型库的合成成功率达到了85%.
- 一个拥有2.71亿成员的易于访问的 (REAL) 异环化学空间被生成,包含独特的化学类型.
- 在该空间内的432种化合物在ChEMBL数据库中被确定为具有生物活性.
结论:
- 平行Groebke-Blackburn-Bienaymé反应是产生广泛和多样化的异环化学空间的强大工具.
- 优化的方法可以有效地获得具有潜在生物相关性的新型化合物.
- 这种方法显著扩大了药物发现工作的可搜索化学空间.
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