Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core

• Autoři: NĚMEC Václav; MAIER Lukáš; BERGER Benedict-Tilman; CHAIKUAD Apirat; DRÁPELA Stanislav; SOUČEK Karel; KNAPP Stefan; PARUCH Kamil
• Rok publikování: 2021
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: European Journal of Medicinal Chemistry
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• www: https://doi.org/10.1016/j.ejmech.2021.113299
• Doi: http://dx.doi.org/10.1016/j.ejmech.2021.113299
• Klíčová slova: Kinase; Inhibitor; Furo[3.2-b]pyridine; HIPK; MU135; MU1787; CLK; MU1210
• Popis: The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe (c) 2021 Published by Elsevier Masson SAS.

Související projekty

• Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
• CZ-­OPENSCREEN: National Infrastructure for Chemical Biology