Design, Synthesis, and Biological Evaluation of Chromone-Based p38 MAP Kinase Inhibitors
| Autor: | Morten Grøtli, Peter Dinér, Fredrik K. Wallner, Per Sunnerhagen, Linda Nilsson Möllers, John P. Alao, Christine Dyrager, Linda Karlsson Kjäll |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Stereochemistry p38 mitogen-activated protein kinases Antineoplastic Agents Breast Neoplasms p38 Mitogen-Activated Protein Kinases Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Moiety IC50 biology Kinase Combinatorial chemistry chemistry Chromones Drug Design Mitogen-activated protein kinase Chromone Cancer cell biology.protein Molecular Medicine Female Drug Screening Assays Antitumor Selectivity |
| Zdroj: | Journal of Medicinal Chemistry. 54:7427-7431 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38α inhibitors with IC50 in the low nanomolar range (e.g., 8a, IC50 = 17 nm). The inhibitors (8a and 8e) showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition (8e) of p38 signaling in human breast cancer cells. |
| Databáze: | OpenAIRE |
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