Synthesis, benzodiazepine receptor binding, and anticonvulsant activity of 2,3-dihydro-3-oxo-5H-pyrido[3,4-b][1,4]benzothiazine-4-carbonitriles
| Autor: | Robert J. Chorvat, James D. Hirsch, Suzanne Evans Radak, James L. Bloss, Stanley S. Tenen, Bipin N. Desai |
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| Rok vydání: | 1983 |
| Předmět: |
Male
Pyridines Stereochemistry medicine.drug_class medicine.medical_treatment Thiazines Drinking Behavior Receptors Cell Surface Benzothiazine Conflict Psychological Mice chemistry.chemical_compound In vivo Drug Discovery Convulsion medicine Animals Potency Receptor Benzodiazepine receptor binding Benzodiazepine Receptors GABA-A Anticonvulsant chemistry Molecular Medicine Anticonvulsants medicine.symptom |
| Zdroj: | Journal of Medicinal Chemistry. 26:845-850 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00360a011 |
| Popis: | A series of oxopyridobenzothiazines (azaphenothiazines) were prepared and evaluated for binding to the benzodiazepine receptor, anticonvulsant activity in the pentylenetetrazole-induced convulsion assay, and, in two cases, ability to increase punished responding in a standard conflict test. While parent compound 1a showed binding affinity comparable to chlorodiazepoxide (CDP), its potency in the anticonvulsant assay and the anticonflict test was considerably weaker than CDP. Of the variety of derivatives synthesized, only the 7-chloro compound 1b showed receptor affinity comparable to 1a with slightly improved in vivo activity. The poor correlation between receptor binding and in vivo activity may be due to variability in absorption or pharmacological responses unrelated to affinity for the benzodiazepine receptor. |
| Databáze: | OpenAIRE |
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