Journal of medicinal chemistry, 2008-06, Vol.51 (11), p.3065-3068
2008
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Details
- Autor(en) / Beteiligte
- Titel
- Discovery of Aryl Aminoquinazoline Pyridones as Potent, Selective, and Orally Efficacious Inhibitors of Receptor Tyrosine Kinase c-Kit
- Ist Teil von
- Journal of medicinal chemistry, 2008-06, Vol.51 (11), p.3065-3068
- Ort / Verlag
- Washington, DC: American Chemical Society
- Erscheinungsjahr
- 2008
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2623eISSN: 1520-4804DOI: 10.1021/jm800188gTitel-ID: cdi_osti_scitechconnect_1006980
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Administration, Oral, Animals, BASIC BIOLOGICAL SCIENCES, Biological and medical sciences, Bones, joints and connective tissue. Antiinflammatory agents, Crystallography, X-Ray, DISEASES, HISTAMINE, Histamine Release - drug effects, Immunomodulators, IN VIVO, INHIBITION, MAST CELLS, Mast Cells - drug effects, Mast Cells - metabolism, Medical sciences, Models, Molecular, Molecular Structure, Pharmacology. Drug treatments, PHOSPHOTRANSFERASES, POTENTIALS, Protein Kinase Inhibitors - chemical synthesis, Protein Kinase Inhibitors - pharmacokinetics, Protein Kinase Inhibitors - pharmacology, Proto-Oncogene Proteins c-kit - metabolism, Pyridones - chemical synthesis, Pyridones - pharmacokinetics, Pyridones - pharmacology, Quinazolines - chemical synthesis, Quinazolines - pharmacokinetics, Quinazolines - pharmacology, Rats, RECEPTORS, RODENTS, Structure-Activity Relationship, TYROSINE