Knoepfel, Thomas, Furet, Pascal, Mah, Robert, Buschmann, Nicole, Leblanc, Catherine, Ripoche, Sebastien, Graus Porta, Diana, Wartmann, Markus and Galuba, Inga (2018) 2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4. ACS Medicinal Chemistry Letters, 9 (3). pp. 215-220. ISSN 19485875

Abstract

As part of a project to identify FGFR4 selective inhibitors, scaffold morphing of a 2-formylquinoline amide hit identified series of 2-formylpyridine ureas (2-FPUs) with improved potency and physicochemical properties. In particular, tetrahydronaphthyridine urea analogues with cellular activities below 30 nM have been identified. Consistent with the hypothesized reversible-covalent mechanism of inhibition, the 2-FPUs exhibited slow binding kinetics, and the aldehyde, as the putative electrophile, could be demonstrated to be a key structural element for activity.

Item Type:	Article
Keywords:	2-Formylpyridines binding kinetics fibroblast growth factor receptor 4 hepatocellular carcinoma kinase inhibitors reversible-covalent binders
Date Deposited:	14 Jul 2018 00:45
Last Modified:	14 Jul 2018 00:45
URI:	https://oak.novartis.com/id/eprint/34446