Serendipitous oxidation product of BIBN4096BS: A potent CGRP receptor antagonist
| Autor: | Daniel R. Schroeder, Vivekananda M. Vrudhula, Charlie M. Conway, Cen Xu, Gene M. Dubowchik, Bireshwar Dasgupta, John E. Macor, Sokhom S. Pin, Edward S. Kozlowski, John R. Torrente |
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| Rok vydání: | 2014 |
| Předmět: |
Molecular Structure
Chemistry Stereochemistry Organic Chemistry Clinical Biochemistry Antagonist Pharmaceutical Science Calcitonin gene-related peptide Biochemistry Piperazines Inhibitory Concentration 50 Calcitonin Gene-Related Peptide Receptor Antagonists Product (mathematics) Drug Discovery Quinazolines Molecular Medicine Biological Assay Oxidation-Reduction Molecular Biology CGRP receptor |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:2744-2748 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2014.04.033 |
| Popis: | An oxidation product (5) formed during the synthesis of BIBN-4096BS (1) was found to be a potent CGRP antagonist (IC50 = 0.11 nM). While 5 was found to be ten-fold less potent than 1, another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7. Alternative conditions which preclude the formation of the oxidation product are described. The activities of 1, 5, 7 and 8 in functional cAMP assay are also discussed. |
| Databáze: | OpenAIRE |
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