Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk)
| Autor: | David J. Maloney, Craig J. Thomas, Juan J. Marugan, Bryan T. Mott, Min Shen, Tom Misteli, William Leister, James Inglese, Paul Shinn, Christopher P. Austin, Cordelle Tanega, Douglas S. Auld |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Stereochemistry Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Peptide Protein Serine-Threonine Kinases Crystallography X-Ray Biochemistry Article CLK1 Structure-Activity Relationship Drug Discovery Structure–activity relationship Amines Protein Kinase Inhibitors Molecular Biology chemistry.chemical_classification Cyclin-dependent kinase 1 Protein-Serine-Threonine Kinases Molecular Structure Kinase Organic Chemistry Dual-specificity kinase Protein-Tyrosine Kinases Enzyme chemistry Drug Design Quinazolines Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:6700-6705 |
| ISSN: | 0960-894X |
| Popis: | A series of substituted 6-arylquinazolin-4-amines were prepared and analyzed as inhibitors of Clk4. Synthesis, structure-activity relationships and the selectivity of a potent analogue against a panel of 402 kinases are presented. Inhibition of Clk4 by these agents at varied concentrations of assay substrates (ATP and receptor peptide) highly suggests that this chemotype is an ATP competitive inhibitor. Molecular docking provides further evidence that inhibition is the result of binding at the kinase hinge region. Selected compounds represent novel tools capable of potent and selective inhibition of Clk1, Clk4, and Dyrk1A. |
| Databáze: | OpenAIRE |
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