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Discovery of 3-phenyl- and 3-N-piperidinyl-isothiazolo[4,3-b] pyridines as highly potent inhibitors of cyclin G-associated kinase

Tijdschriftbijdrage - Tijdschriftartikel

Structural modifications at position 3 of the isothiazolo[4,3-b]pyridine scaffold afforded a new series of cyclin G-associated kinase (GAK) inhibitors. It was shown that the insertion of a carboxamide residue at position 3 of a phenyl or piperidinyl moiety generated potent GAK inhibitors with IC50 values in a low nanomolar range. This potent GAK binding affinity was rationalized by molecular modelling demonstrating that the carboxamide moiety engages in an extra hydrogen bond with GAK. Moreover, this new series of compounds was also endowed with antiviral activity against dengue virus, highlighting the potential utility of GAK as a target for the development of antiviral drugs.
Tijdschrift: European Journal of Medicinal Chemistry
ISSN: 0223-5234
Volume: 213
Jaar van publicatie:2021
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:3
CSS-citation score:2
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open