Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines
| Autor: | Michael J. Reno, Alex G. Waterson, David E. Uehling, David W. Rusnak, Robert J. Griffin, Scott Howard Dickerson, Holly Kathleen Emerson, Robert D. Hubbard, Keith R. Hornberger, Edgar R. Wood |
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| Rok vydání: | 2008 |
| Předmět: |
Receptor
ErbB-2 Clinical Biochemistry Pharmaceutical Science Biochemistry Receptor tyrosine kinase Cell Line Mice Structure-Activity Relationship ErbB Drug Discovery Structure–activity relationship Animals Epidermal growth factor receptor Receptor Molecular Biology chemistry.chemical_classification biology Chemistry Kinase Organic Chemistry ErbB Receptors Enzyme Pyrimidines biology.protein Molecular Medicine Signal transduction Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry letters. 18(21) |
| ISSN: | 1464-3405 |
| Popis: | A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modification of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose. |
| Databáze: | OpenAIRE |
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