Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core
| Autor: | Václav Němec, Stefan Knapp, Apirat Chaikuad, Benedict-Tilman Berger, Stanislav Drápela, Kamil Paruch, Karel Souček, Lukáš Maier |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pyridines
Stereochemistry Chemical biology Crystal structure Protein Serine-Threonine Kinases Crystallography X-Ray 01 natural sciences CLK1 Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Drug Discovery Pyridine Animals Humans Furans Protein Kinase Inhibitors 030304 developmental biology Pharmacology 0303 health sciences Molecular Structure 010405 organic chemistry Kinase Chemistry Organic Chemistry General Medicine Highly selective 0104 chemical sciences 3. Good health MCF-7 Cells Pharmacophore Carrier Proteins Protein Binding |
| Zdroj: | European Journal of Medicinal Chemistry. 215:113299 |
| ISSN: | 0223-5234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect