Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway

• Autoři: NĚMEC Václav; HYLSOVÁ Michaela; MAIER Lukáš; FLEGEL Jana; SIEVERS Sonja; ZIEGLER Slava; SCHRÖDER Martin; BERGER Benedict-Tilman; CHAIKUAD Apirat; VALČÍKOVÁ Barbora; ULDRIJAN Stjepan; DRÁPELA Stanislav; SOUČEK Karel; WALDMANN Hebert; KNAPP Stefan; PARUCH Kamil
• Rok publikování: 2019
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Angewandte Chemie International Edition
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• www: https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201810312
• Doi: http://dx.doi.org/10.1002/anie.201810312
• Klíčová slova: biological activity; chemical probes; heterocycles; inhibitors; kinases
• Popis: Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

Související projekty

• CZ-­OPENSCREEN: National Infrastructure for Chemical Biology
• Finální profilace vysoce účinných a selektivních inhibitorů proteinových kináz CLK a CK1
• Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
• Molekulární a buněčná biologie pro biomedicínské vědy