基于microtiter板的化学和现场查:SuFEx支持的选择性ACHE抑制剂的领先发现
Kun Tang1, Huan-Huan Li2, Chengyao Wu2
1School of Pharmacy, Macau University of Science and Technology, Macau, P.R. China.
Journal of enzyme inhibition and medicinal chemistry
|July 28, 2023
概括
一种新的硫化物交换 (SuFEx) 点击化学方法有效合成硫胺. 这种方法确定了T14-A24,一种强大的乙胆酶抑制剂,在体内表现出神经保护作用并改善认知功能.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 神经科学是一个神经科学.
背景情况:
- 硫化物交换 (SuFEx) 点击化学通过硫链接促进模块化合成.
- 开发高效的硫胺库合成方法对于药物发现至关重要.
- 乙胆酶 (AChE) 抑制剂是认知障碍的重要治疗点.
研究的目的:
- 开发一种使用SuFEx点击化学的硫胺的高效合成和选方法.
- 确定具有潜在治疗应用的新型ACHE抑制剂.
- 评估已识别的化合物的神经保护和认知增强特性.
主要方法:
- 苏菲克斯 (SuFEx) 在硫尼尔化物和氨基之间进行点击反应,以合成硫胺库.
- 在现场选合成化合物的ChE抑制活性.
- 在体外和体内测试以评估类似药物的特性,神经保护和认知功能.
主要成果:
- 通过SuFEx点击化学实现了硫胺的高效皮科莫拉级合成.
- 化合物T14-A24被确定为一种可逆,竞争性和选择性的ACHE抑制剂 (Ki = 22 nM).
- 在体内,T14-A24表现出有利的血脑屏障透,神经保护和改善认知障碍.
结论:
- SuFEx点击反应为发现化合物,特别是ACHE抑制剂提供了快速有效的途径.
- T14-A24显示出作为治疗神经退行性疾病与认知能力下降相关的治疗剂的显著潜力.
- 这种方法加速了具有理想药理特征的候选药物的识别和开发.
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