Publication details

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

Authors

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

Type Article in Periodical
Magazine / Source Angewandte Chemie International Edition
MU Faculty or unit

Faculty of Science

Citation
Web https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201810312
Doi http://dx.doi.org/10.1002/anie.201810312
Keywords biological activity; chemical probes; heterocycles; inhibitors; kinases
Description 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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