Novel pyrazolopyrimidines as highly potent B-Raf inhibitors
| Autor: | Nancy Torres, Eileen Frommer, Bloom Jonathan David, Karen Collins, Dunnick Alejandro Lee, George Diamantidis, Yongbo Hu, Minu Dutia, Christoph W. Zapf, Zhang Chunchun, Darrin William Hopper, Dan Maarten Berger, Donald Wojciechowicz, Dennis Powell, Martin Di Grandi, Jeremy I. Levin |
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| Rok vydání: | 2009 |
| Předmět: |
Proto-Oncogene Proteins B-raf
Pyridines Isostere Stereochemistry Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Chemical synthesis chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Enzyme Inhibitors Cytotoxicity Molecular Biology Cell Proliferation chemistry.chemical_classification Indazole biology Bicyclic molecule Cell growth Organic Chemistry Pyrimidines Enzyme chemistry Enzyme inhibitor biology.protein Pyrazoles Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:6957-6961 |
| ISSN: | 0960-894X |
| Popis: | A novel series of pyrazolo[1,5-a]pyrimidines bearing a 3-hydroxyphenyl group at C(3) and substituted tropanes at C(7) have been identified as potent B-Raf inhibitors. Exploration of alternative functional groups as a replacement for the C(3) phenol demonstrated indazole to be an effective isostere. Several compounds possessing substituted indazole residues, such as 4e, 4p, and 4r, potently inhibited cell proliferation at submicromolar concentrations in the A375 and WM266 cell lines, and the latter two compounds also exhibited good therapeutic indices in cells. |
| Databáze: | OpenAIRE |
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