Tyrphostins. 5. Potent Inhibitors of Platelet-Derived Growth Factor Receptor Tyrosine Kinase: Structure−Activity Relationships in Quinoxalines, Quinolines, and Indole Tyrphostins
| Autor: | Gerald M. McMahon, Frank D. Bohmer, Harald App, Aviv Gazit, Jefferey Chen, Alexander Levitzki |
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| Rok vydání: | 1996 |
| Předmět: |
Indoles
Platelet-derived growth factor Stereochemistry Tyrphostins Mice Structure-Activity Relationship chemistry.chemical_compound Growth factor receptor Quinoxalines Nitriles Drug Discovery Animals Structure–activity relationship Receptors Platelet-Derived Growth Factor Enzyme Inhibitors Phosphorylation Platelet-Derived Growth Factor Indole test Epidermal Growth Factor Molecular Structure biology Cell Membrane Receptor Protein-Tyrosine Kinases 3T3 Cells chemistry Biochemistry Enzyme inhibitor Quinolines biology.protein Molecular Medicine Indicators and Reagents Tyrosine kinase Platelet-derived growth factor receptor |
| Zdroj: | Journal of Medicinal Chemistry. 39:2170-2177 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolines were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at different sites. The inhibitors showed selectivity for PDGF and were not active against EGF receptor and HER-2/c-ErbB-2 receptor. |
| Databáze: | OpenAIRE |
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