Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase

ChemMedChem
Christopher R M AsquithWilliam J Zuercher

Abstract

4-Anilinoquinolines were identified as potent and narrow-spectrum inhibitors of the cyclin G associated kinase (GAK), an important regulator of viral and bacterial entry into host cells. Optimization of the 4-anilino group and the 6,7-quinoline substituents produced GAK inhibitors with nanomolar activity, over 50 000-fold selectivity relative to other members of the numb-associated kinase (NAK) subfamily, and a compound (6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine; 49) with a narrow-spectrum kinome profile. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious and systemic diseases.

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Citations

Aug 20, 2019·ChemMedChem·Christopher R M AsquithWilliam J Zuercher
Oct 16, 2019·Antimicrobial Agents and Chemotherapy·María Ayelén CarabajalEleonora García Véscovi
Nov 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christopher R M AsquithWilliam J Zuercher
Feb 16, 2020·Medicinal Research Reviews·Xingyue Ji, Zhuorong Li
Apr 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christopher R M AsquithWilliam J Zuercher
Sep 26, 2020·Frontiers in Immunology·Siyuan ChenWenkai Ren
Jan 27, 2021·European Journal of Medicinal Chemistry·Belén Martinez-GualdaSteven De Jonghe
Jul 8, 2020·Bioorganic & Medicinal Chemistry Letters·Sirle SaulChristopher R M Asquith
Aug 6, 2019·Bioorganic & Medicinal Chemistry Letters·Christopher R M AsquithWilliam J Zuercher
May 11, 2021·Journal of Medicinal Chemistry·Javier García-CárcelesAna Martínez
Feb 16, 2019·Journal of Medicinal Chemistry·Christopher R M AsquithWilliam J Zuercher
Mar 19, 2020·ACS Medicinal Chemistry Letters·Carrow WellsAlison D Axtman
Sep 4, 2021·Journal of Medicinal Chemistry·Ricardo A M SerafimMatthias Gehringer

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