Development of a Novel Series of Trialkoxyaryl Derivatives as Specific and Competitive Antagonists of Platelet Activating Factor
| Autor: | N. J. Cheesman, Demaine Da, M. A. Brockwell, D. A. Sawyer, H. F. Hodson, R. M. Beams, G. J. Blackwell, L.G. Garland, P. J. Islip, R. M. Hyde |
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| Rok vydání: | 1995 |
| Předmět: |
Blood Platelets
Male chemistry.chemical_classification Binding Sites Platelet-activating factor Molecular model Stereochemistry Iodide Chemical synthesis Quaternary Ammonium Compounds Structure-Activity Relationship chemistry.chemical_compound Non-competitive inhibition chemistry Drug Discovery Animals Molecular Medicine Platelet Rabbits Platelet Activating Factor Receptor Lead compound Cells Cultured Platelet Aggregation Inhibitors |
| Zdroj: | Journal of Medicinal Chemistry. 38:2130-2137 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | The synthesis and structure-activity relationship (SAR) analysis of a novel series of trialkoxyaryl derivatives, as specific and competitive inhibitors of platelet activating factor (PAF), are described. Molecular modeling comparisons of PAF with the known antagonists Ginkgolide B and L-652731 led to the selection of N-[2-[(3,4,5-trimethoxybenzoyl)oxy]ethyl]-N,N,N-trimethylammonium iodide (1) from the Wellcome registry of compounds and to the synthesis of the lead compound N-[2-[[4-(hexyloxy)-3,5-dimethoxybenzoyl]oxy]ethyl]-N,N,N-trimethylammonium iodide (3, pK b 5.43). Further SAR considerations directed the design to 2-(hexyloxy)-1,3-dimethoxy-5-[4-(4-methylthiazol-5-yl)butyl]benzene (38) (pK b 7.14), a novel, specific, and competitive inhibitor of the PAF receptor in rabbit-washed platelets. |
| Databáze: | OpenAIRE |
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