Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- biological activity, chemical probes, heterocycles, inhibitors, kinases,
- MeSH
- Furans chemistry MeSH
- Inhibitory Concentration 50 MeSH
- Protein Kinase Inhibitors chemical synthesis chemistry pharmacology MeSH
- Small Molecule Libraries chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Molecular Structure MeSH
- Hedgehog Proteins chemistry MeSH
- Pyridines chemistry MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Furans MeSH
- furo(3,2-b)pyridine MeSH Browser
- Protein Kinase Inhibitors MeSH
- Small Molecule Libraries MeSH
- Hedgehog Proteins MeSH
- Pyridines MeSH
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.
Department of Biology Faculty of Medicine Masaryk University Kamenice 5 Brno 625 00 Czech Republic
Department of Chemistry CZ Openscreen Masaryk University Kamenice 5 Brno 625 00 Czech Republic
Department of Cytokinetics Institute of Biophysics CAS Královopolská 135 Brno 612 65 Czech Republic
References provided by Crossref.org
Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential
CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells