Potent Kv1.3 inhibitors from correolide—modification of the C18 position
| Autor: | Gloria C. Koo, Laurie A. Castonguay, Mary Jo Staruch, Randal M. Bugianesi, John P. Felix, George A. Doss, Robert S. Slaughter, Marty S. Springer, Andrew Kotliar, Sookhee Ha, Kathleen M. Rupprecht, William H. Parsons, Gregory J. Kaczorowski, Kashmira Shah, Shouwu Miao, Jianming Bao, Maria L. Garcia, Frank Kayser, Robert K. Baker |
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| Rok vydání: | 2005 |
| Předmět: |
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Molecular Stereochemistry T-Lymphocytes T cell Clinical Biochemistry Pharmaceutical Science Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Potassium Channel Blockers medicine Humans Channel blocker Molecular Biology Cell Proliferation Kv1.3 Potassium Channel Natural product Cell growth Organic Chemistry Triterpenes Potassium channel In vitro medicine.anatomical_structure chemistry Potassium Channels Voltage-Gated Molecular Medicine Biological Assay Ion Channel Gating Enone Immunosuppressive Agents Ion channel blocker |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 15:447-451 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2004.10.058 |
| Popis: | Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure–activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation. |
| Databáze: | OpenAIRE |
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