946491-05-0Relevant academic research and scientific papers
Further studies on ethenyl and ethynyl-4-phenylamino-3- quinolinecarbonitriles: Identification of a subnanomolar Src kinase inhibitor
Sosa, Ana Carolina Barrios,Boschelli, Diane H.,Wu, Biqi,Wang, Yan,Golas, Jennifer M.
, p. 1743 - 1747 (2005)
Several new ethynyl- and ethenyl-4-phenylamino-3-quinolinecarbonitriles were synthesized and tested for Src inhibition. Derivatives bearing an ethenyl or ethynyl substituent at C-6 showed decreased Src inhibitory activity. Incorporation of an ethenylpyridine N-oxide group at C-7 provided 20b, a 0.6 nM inhibitor of Src enzymatic activity with excellent cellular potency.
Potent antiviral activity of novel multi-substituted 4-anilinoquin(az)olines
Saul, Sirle,Pu, Szu-Yuan,Zuercher, William J.,Einav, Shirit,Asquith, Christopher R.M.
, (2020/06/08)
Screening a series of 4-anilinoquinolines and 4-anilinoquinazolines enabled identification of potent novel inhibitors of dengue virus (DENV). Preparation of focused 4-anilinoquinoline/quinazoline scaffold arrays led to the identification of a series of high potency 6-substituted bromine and iodine derivatives. The most potent compound 6-iodo-4-((3,4,5-trimethoxyphenyl)amino)quinoline-3-carbonitrile (47) inhibited DENV infection with an EC50 = 79 nM. Crucially, these compounds showed very limited toxicity with CC50 values >10 μM in almost all cases. This new promising series provides an anchor point for further development to optimize compound properties.
Design and Analysis of the 4-Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure-Activity Relationships
Asquith, Christopher R. M.,Bennett, James M.,Elkins, Jonathan M.,Laitinen, Tuomo,Poso, Antti,Tizzard, Graham J.,Wells, Carrow I.,Zuercher, William J.
, (2019/12/03)
The 4-anilinoquinoline and 4-anilinoquinazoline ring systems have been the focus of significant efforts in prior kinase drug discovery programs, which have led to approved medicines. Broad kinome profiles of these compounds have now been assessed with the advent of advanced screening technologies. These ring systems, while originally designed for specific targets including epidermal growth factor receptor (EGFR), but actually display a number of potent collateral kinase targets, some of which have been associated with negative clinical outcomes. We have designed and synthesized a series of 4-anilinoquin(az)olines in order to better understand the structure-activity relationships of three main collateral kinase targets of quin(az)oline-based kinase inhibitors: cyclin G associated kinase (GAK), STE20-like serine/threonine-protein kinase (SLK) and serine/threonine-protein kinase 10 (STK10). This was achieved through a series of quantitative structure-activity relationship (QSAR) analysis, water mapping of the kinase ATP binding sites and extensive small-molecule X-ray structural analysis.
