Thienylpyrazoloquinolines with high affinity to benzodiazepine receptors: continuous shift from inverse agonist to agonist properties depending on the size of the alkyl substituent
| Autor: | Masami Eigyo, Susumu Takada, Shunji Murata, H. Shindo, Akira Matsushita |
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| Rok vydání: | 1989 |
| Předmět: |
Agonist
Male Chemical Phenomena medicine.drug_class Stereochemistry Substituent Thiophenes chemistry.chemical_compound Mice Structure-Activity Relationship Seizures Drug Discovery medicine Inverse agonist Animals Alkyl chemistry.chemical_classification Diazepam Molecular Structure Chemistry GABAA receptor Antagonist Drug Synergism Receptors GABA-A Affinities Quinolines Molecular Medicine Pentylenetetrazole Pyrazoles |
| Zdroj: | Journal of medicinal chemistry. 32(6) |
| ISSN: | 0022-2623 |
| Popis: | 2-(5-Alkylthien-3-yl)-(1),2-(4-alkylthien-2-yl)-(2), and 2-(5-alkylthien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolines (3) were prepared in four steps starting from ethyl 4-chloroquinoline-3-carboxylate (4) and hydrazinothiophene-carboxylates 5, 8, and 9. All the assayed compounds possessed high affinities for benzodiazepine receptors (Ki = 0.3-2.6 nM). The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of pentylenetetrazole-induced convulsions, respectively. Introduction of alkyl groups of different sizes into the unsubstituted inverse agonistic compounds results in a corresponding shift in the activity from an inverse agonist to an antagonist to an agonist. The susceptibility of such a shift increases in the order of 1 less than 2 less than 3. This tendency may be explained by slight differences in the geometry of the alkyl substituents among the three series. |
| Databáze: | OpenAIRE |
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