Triazolobenzo- and triazolothienodiazepines as potent antagonists of platelet activating factor
| Autor: | Catherine Maresca, T. Flynn, Armin Walser, Margaret O'Donnell, Bob Yaremko, Carl J. Mason, Herman J. Crowley |
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| Rok vydání: | 1991 |
| Předmět: |
Blood Platelets
Male Chemical Phenomena Stereochemistry Bronchoconstriction Guinea Pigs Molecular Conformation Thiophenes chemistry.chemical_compound Benzodiazepines Structure-Activity Relationship Dogs In vivo Oral administration Drug Discovery Potency Animals Platelet Activating Factor Short duration Platelet-activating factor Molecular Structure Chemistry Biological activity Azepines Triazoles In vitro Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry. 34(3) |
| ISSN: | 0022-2623 |
| Popis: | A series of [1,2,4]triazolo[4,3-alpha][1,4]benzodiazepines bearing an ethynyl functionality at the 8-position and the isosteric thieno[3,2-f][1,2,4]triazolo[4,3-alpha][1,4]diazepines were prepared and evaluated as antagonists of platelet activating factor. The effects of substitution were explored in in vitro and in vivo test systems designed to measured PAF-antagonistic activity. Results are discussed and compared with previously published data. Many of the compounds had activity superior to WEB 2086, compound 1. In general, the thieno analogues exhibited better oral activity than the corresponding benzodiazepines. The duration of activity upon oral administration was modulated by the substitution on the acetylenic side chain. Compounds 71 and 81 were selected for further pharmacological evaluation as a result of their good oral potency and exceptionally long duration of action. |
| Databáze: | OpenAIRE |
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