Synthesis of (2S, 5S)- trans-5-(4- fluorophenoxymethyl) -2-(1-N-hydroxy ureidyl-3-butyn-4-yl) -tetrahydrofuran– (CMI-977)
| Autor: | Andappan Murugaiah Subbaiah Murugaiah, Kashinath Sadalapure, Mukund K. Gurjar, Susanta Adhikari, Mukund S. Chorghade, Palakodety Radha Krishna, Sista Venkata Sai Lalitha |
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| Rok vydání: | 1999 |
| Předmět: |
chemistry.chemical_classification
Leukotriene biology Chemistry General Chemical Engineering Leukotriene A4 General Chemistry respiratory system Transmembrane protein Epithelium Cofactor chemistry.chemical_compound medicine.anatomical_structure Enzyme Biochemistry medicine biology.protein Secretion Arachidonic acid |
| Zdroj: | Pure and Applied Chemistry. 71:1071-1074 |
| ISSN: | 1365-3075 0033-4545 |
| Popis: | Three novel, versatile and cost-effective syntheses of the title compound, a potent 5-LO inhibitor, have been described. Asthma is a chronic inflammatory disease complicated by periodic acute inflammatory changes. Morphologically, asthma is characterised by infiltration of the bronchial mucosa and epithelium with activated T cells, mast cells, eosinophils, neutrophils and macrophages. The complexity of the interactions between these and other inflammatory cells, and the interactions between the pro- inflammatory mediators which they secrete, remains to be fully elucidated. In the past the conventional view has been that targeting a single group of mediators for pharmacological blockade would be unlikely to confer significant benefit. This view, however, is not compatible with the evidence generated in the past decade regarding the unexpectedly high efficacy in clinical trials of drugs that block the synthesis or the activity of the leukotriene mediators. Leukotrienes (LT) are metabolites of arachidonic acid produced by the activity of 5-lipoxygenase (5- LO). Arachidonic acid is presented to the 5-LO enzyme by 5-lipoxygenase-activating protein, a cofactor resident in the nuclear membrane; the interaction leads to the formation of the unstable intermediate, leukotriene A4. LTA4 is further converted either to the chemotaxin LTB4 by LTA4 hydrolase, or to LTC4 by the transmembrane enzyme LTC4 synthatase. Further conversion of LTC4 to LTD4 and then to LTE4occurs by the action of enzymes ubiquitous in both tissues and circulation. |
| Databáze: | OpenAIRE |
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