Identification and optimization of 4-anilinoquinolines as inhibitors of cyclin G associated kinase
Identification and optimization of 4-anilinoquinolines as inhibitors of cyclin G associated kinase
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.
anilinoquinolines, antibacterial agents, chemical probes, cyclin G associated kinase (GAK)
1-20
Asquith, Christopher R.M.
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Laitinen, Tuomo
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Bennett, James M.
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Godoi, Paulo H.
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East, Michael P.
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Tizzard, Graham J.
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Graves, Lee M.
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Johnson, Gary L.
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Dornsife, Ronna E.
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Wells, Carrow I.
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Elkins, Jonathan M.
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Wilson, Timothy M.
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Zuercher, William J.
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Asquith, Christopher R.M.
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Laitinen, Tuomo
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Bennett, James M.
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Godoi, Paulo H.
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East, Michael P.
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Tizzard, Graham J.
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Graves, Lee M.
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Johnson, Gary L.
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Dornsife, Ronna E.
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Wells, Carrow I.
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Elkins, Jonathan M.
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Wilson, Timothy M.
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Zuercher, William J.
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Asquith, Christopher R.M., Laitinen, Tuomo, Bennett, James M., Godoi, Paulo H., East, Michael P., Tizzard, Graham J., Graves, Lee M., Johnson, Gary L., Dornsife, Ronna E., Wells, Carrow I., Elkins, Jonathan M., Wilson, Timothy M. and Zuercher, William J.
(2017)
Identification and optimization of 4-anilinoquinolines as inhibitors of cyclin G associated kinase.
ChemMedChem, 2017 (12), .
(doi:10.1002/cmdc.201700663).
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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Accepted/In Press date: 26 October 2017
e-pub ahead of print date: 27 November 2017
Keywords:
anilinoquinolines, antibacterial agents, chemical probes, cyclin G associated kinase (GAK)
Identifiers
Local EPrints ID: 416465
URI: http://eprints.soton.ac.uk/id/eprint/416465
ISSN: 1860-7179
PURE UUID: 41f76288-1a54-4921-9827-fb0249a7bc86
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Date deposited: 19 Dec 2017 17:30
Last modified: 16 Mar 2024 06:02
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Contributors
Author:
Christopher R.M. Asquith
Author:
Tuomo Laitinen
Author:
James M. Bennett
Author:
Paulo H. Godoi
Author:
Michael P. East
Author:
Lee M. Graves
Author:
Gary L. Johnson
Author:
Ronna E. Dornsife
Author:
Carrow I. Wells
Author:
Jonathan M. Elkins
Author:
Timothy M. Wilson
Author:
William J. Zuercher
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