[Studies on the synthesis of condensed pyridazine derivatives. I. Synthesis and benzodiazepine receptor binding studies of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds]
| Autor: | Kenji Morita, Tetsuya Tahara, Tohru Nakao, Shuzo Takehara, Minoru Kawakami, Yasuto Morimoto |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.drug_class Stereochemistry Pharmaceutical Science Bicuculline Pyridazine chemistry.chemical_compound Mice Structure-Activity Relationship medicine Structure–activity relationship Animals Receptor Benzodiazepine receptor binding Pharmacology Benzodiazepine Dose-Response Relationship Drug Chemistry Ligand binding assay Rats Inbred Strains Receptors GABA-A Rats Pyridazines Membrane Anti-Anxiety Agents Diazepam medicine.drug |
| Zdroj: | Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 110(8) |
| ISSN: | 0031-6903 |
| Popis: | A series of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes. Among them, compounds bearing 4-methoxyphenyl, 4-chlorophenyl, or 4-methylphenyl group at the position-2 were found to have high affinity to the benzodiazepine receptor. 2-(4-Methoxyphenyl)-9-methyl- and 2-(4-methoxyphenyl)-9-methoxy-4,4a,5,6-tetrahydrobenzo[h]cinnolin- 3(2H)-ones (8b-14 and 8b-15, respectively) showed a potent affinity comparable to that of diazepam. These results suggest that a topographical planarity or pseudoplanarity of these molecules is essential for high affinity to the benzodiazepine receptor. The structure-activity relationships are discussed. |
| Databáze: | OpenAIRE |
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