1085443-95-3Relevant academic research and scientific papers
Targeting the Water Network in Cyclin G-Associated Kinase (GAK) with 4-Anilino-quin(az)oline Inhibitors
Asquith, Christopher R. M.,Bennett, James M.,Elkins, Jonathan M.,Laitinen, Tuomo,Poso, Antti,Tizzard, Graham J.,Wells, Carrow I.,Willson, Timothy M.
, (2020)
Water networks within kinase inhibitor design and more widely within drug discovery are generally poorly understood. The successful targeting of these networks prospectively has great promise for all facets of inhibitor design, including potency and selectivity for the target. Herein, we describe the design and testing of a targeted library of 4-anilinoquin(az)olines for use as inhibitors of cyclin G-associated kinase (GAK). GAK cellular target engagement assays, ATP binding-site modelling and extensive water mapping provide a clear route to access potent inhibitors for GAK and beyond.
Optimization of 4-anilinoquinolines as dengue virus inhibitors
Asquith, Christopher R. M.,Einav, Shirit,Huang, Pei-Tzu,Saul, Sirle
supporting information, (2021/12/17)
Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (12), 6-bromo-N-(5-fluoro-1H-indazol-6-yl)quinolin-4-amine (50) and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (52), with EC50 values of 0.63–0.69 μM for DENV infection. These compound libraries demonstrated very limited toxicity with CC50 values greater than 10 μM in almost all cases. Additionally, the lead compounds were screened for activity against VEEV and demonstrated activity in the low single-digit micromolar range, with 50 and 52 demonstrating EC50 s of 2.3 μM and 3.6 μM, respectively. The promising results presented here highlight the potential to further refine this series in order to develop a clinical compound against DENV, VEEV, and potentially other emerging viral threats.
NOVEL SULPHOXIMINE-SUBSTITUTED QUINAZOLINE AND QUINAZOLINE DERIVATIVES AS KINASE INHIBITORS
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Page/Page column 36-37, (2009/01/20)
The present invention relates to a quinoline or quinazoline derivative having the general formula (A): in which R3, R4, W, Y and Q are indicated in the description and the claims, the use of the compounds of the general formula (A) f
