Synthesis and LTD4-antagonist activity of desamino-2-nor-leukotriene analogs
| Autor: | Barry M. Weichman, Jeris F. DeVan, Thomas W. Ku, R. M. Muccitelli, Carl D. Perchonock, Stephanie S. Tucker, Beth W. Volpe, Mary E. McCarthy, M A Wasserman, Irene Nijole Uzinskas, William E. Bondinell, Lynne M. Vickery, John G. Gleason |
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| Rok vydání: | 1985 |
| Předmět: |
chemistry.chemical_classification
Meclofenamic Acid Leukotriene Contraction (grammar) Stereochemistry Guinea Pigs Antagonist Peptide respiratory system Biochemistry Chemical synthesis Guinea pig Trachea Structure-Activity Relationship Endocrinology chemistry Potency Animals Carbachol Indicators and Reagents SRS-A Muscle Contraction |
| Zdroj: | Prostaglandins. 29(1) |
| ISSN: | 0090-6980 |
| Popis: | A series of desamino-2-nor-leukotriene analogs has been prepared by the reaction of various thiols with several methyl trans-4,5-epoxy-6Z-alkenoates, followed by deprotection. The products were assessed for their ability to antagonize the LTD4-induced contraction of the isolated guinea pig trachea. Several compounds displayed potent leukotriene antagonist activity, i.e., KB values in the sub-micro-molar range, while only minimally affecting basal airway tone. The most potent analog, 4-hydroxy-5-(2-carboxyethylthio)-6Z-nonadecenoic acid (5) , antagonized both LTD4- and LTE4-induced contractions of the trachea in an apparently competitive fashion. These agents possess increased potency relative to SK&F 101132 (1) , the first leukotriene analog identified as having LT-antagonist activity. Thus, these results demonstrate that deletion of the peptide amino group can produce leukotriene analogs which have minimal intrinsic contractile activity on the isolated guinea pig trachea, yet possess potent leukotriene-antagonistic effects. |
| Databáze: | OpenAIRE |
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