131467-94-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of new Axl kinase inhibitors containing 1,3,4-oxadiazole acetamide moiety as novel linker
Xu, Congjun,Han, Yufei,Xu, Sicong,Wang, Ruxin,Yue, Ming,Tian, Yu,Li, Xiaofan,Zhao, Yanfang,Gong, Ping
, (2019/12/09)
Using the principle of bioisosteric replacement, we present a structure-based design approach to obtain new Axl kinase inhibitors with significant activity at the kinase and cellular levels. Through a stepwise structure-activity relationships exploration, a series of 6,7-disubstituted quinoline derivatives, which contain 1,3,4-oxadiazol acetamide moiety as novel Linker, were ultimately synthesized with Axl as the primary target. Most of them exhibited moderate to excellent activity, with IC50 values ranging from 0.032 to 1.54 μM against the tested cell lines. Among them, the most promising compound 47e, as an Axl kinase inhibitor (IC50 = 10 nM), shows remarkable cytotoxicity against A549, HT-29, PC-3, MCF-7, H1975 and MDA-MB-231 cell lines. More importantly, 47e also shows a significant inhibitory effect on EGFR-TKI resistant NSCLC cell lines H1975/gefitinib. Meanwhile, this study provides a novel type of linker for Axl kinase inhibitors, namely 1,3,4-oxadiazol acetamide moiety, which is out of the scope of the “5- atoms role ".
Synthesis of 5-aryl-1,3,4-oxadiazolyl-2-acetic acids
Janda, Lubomir
, p. 411 - 416 (2007/10/03)
Ethyl (1H-tetrazol-5-yl)acetate is acylated with aroyl chlorides and heteroaroyl chlorides in pyridine. The intermediate acyltetrazoles undergo thermal degradation to ethyl (5-aryl-1,3,4-oxadiazol-2-yl)acetates and (5-heteroaryl-1,3,4-oxadiazol-2-yl)acetates, respectively, in good yields. The corresponding acetic acids are obtained by potassium hydroxide mediated hydrolysis of the esters in anhydrous ethanol.
