Furo[3,2‐b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway |
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Authors: | Vclav Nmec Michaela Hylsov Luk Maier Jana Flegel Sonja Sievers Slava Ziegler Martin Schrder Benedict‐Tilman Berger Apirat Chaikuad Barbora Val
íkov Stjepan Uldrijan Stanislav Drpela Karel Sou
ek Herbert Waldmann Stefan Knapp Kamil Paruch |
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Institution: | Václav Němec,Michaela Hylsová,Luká? Maier,Jana Flegel,Sonja Sievers,Slava Ziegler,Martin Schröder,Benedict‐Tilman Berger,Apirat Chaikuad,Barbora Val?íková,Stjepan Uldrijan,Stanislav Drápela,Karel Sou?ek,Herbert Waldmann,Stefan Knapp,Kamil Paruch |
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Abstract: | Reported is the identification of the furo3,2‐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 furo3,2‐b]pyridine scaffold by copper‐mediated oxidative cyclization. Optimization of the subseries containing 3,5‐disubstituted furo3,2‐b]pyridines afforded potent, cell‐active, and highly selective inhibitors of CLKs. Profiling of the kinase‐inactive subset of 3,5,7‐trisubstituted furo3,2‐b]pyridines revealed sub‐micromolar modulators of the Hedgehog pathway. |
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Keywords: | Biologische Aktivitä t Chemische Sonden Heterocyclen Inhibitoren Kinasen |
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