Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core
Language English Country France Media print-electronic
Document type Journal Article
PubMed
33636538
DOI
10.1016/j.ejmech.2021.113299
PII: S0223-5234(21)00148-3
Knihovny.cz E-resources
- Keywords
- CLK, Furo[3,2-b]pyridine, HIPK, Inhibitor, Kinase, MU1210, MU135, MU1787,
- MeSH
- Furans chemical synthesis metabolism pharmacology MeSH
- Protein Kinase Inhibitors chemical synthesis metabolism pharmacology MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Molecular Structure MeSH
- Mice MeSH
- Protein Serine-Threonine Kinases antagonists & inhibitors metabolism MeSH
- Pyridines chemical synthesis metabolism pharmacology MeSH
- Carrier Proteins antagonists & inhibitors metabolism MeSH
- Protein Binding MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Furans MeSH
- HIPK1 protein, human MeSH Browser
- HIPK2 protein, human MeSH Browser
- Protein Kinase Inhibitors MeSH
- Protein Serine-Threonine Kinases MeSH
- Pyridines MeSH
- Carrier Proteins MeSH
The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe.
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