伊萨丁
化学
奥西多尔
药效团
组合化学
丁酰胆碱酯酶
小分子
计算生物学
药理学
生物化学
酶
乙酰胆碱酯酶
有机化学
阿切
医学
催化作用
生物
作者
Carolina S. Marques,Óscar López,Luisa Leitzbach,J. Fernandez‐Bolanos,Holger Stark,Anthony J. Burke
出处
期刊:Synthesis
[Georg Thieme Verlag KG]
日期:2022-02-16
卷期号:54 (19): 4304-4319
被引量:5
标识
DOI:10.1055/s-0041-1737343
摘要
Abstract In the last decade, our group has been very active at developing and assaying complex libraries of scaffolds with a focus on their potential to identify bioactive drug candidates for neurodegenerative diseases, particularly Alzheimer’s disease (AD). Attention has been focused on isatin-based oxindole scaffolds, for which promising results concerning butyrylcholinesterase (BuChE) inhibitory activity have previously been obtained. Considering some published reports and detailed analysis of the pharmacophores of commercially available drugs for AD (powerful cholinesterase (ChE) inhibitors), we performed a strategic structural modification of the isatin core and generated a new family of isatin-based oxindole hybrids (27 new compounds) possessing crucial key functional units in their framework. The syntheses were accomplished using multiple approaches, including simple N-alkylation reactions, copper-catalyzed amination reactions, and click chemistry. The resulting library was evaluated on ChE and MAO enzymes, both of which are involved in the pathophysiology of neurodegeneration. IC50 values of 1.6 and 2.6 μM (BuChE assays), were achieved for the best inhibitors.
科研通智能强力驱动
Strongly Powered by AbleSci AI