Informace o publikaci

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

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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

Citace
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.
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