Thienylpyrazoloquinolines: potent agonists and inverse agonists to benzodiazepine receptors
| Autor: | H. Shindo, Susumu Takada, Haruyuki Shintaku, Takashi Sasatani, Nobuo Chomei, Akira Matsushita, Masami Eigyo, Kazuo Kawasaki, Yukio Takahara, Shunji Murata |
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| Rok vydání: | 1988 |
| Předmět: |
Agonist
Chemical Phenomena medicine.drug_class Stereochemistry Thiophenes Structure-Activity Relationship Drug Discovery medicine Animals Inverse agonist Receptor Cerebral Cortex Diazepam GABAA receptor Chemistry Antagonist Rats Inbred Strains Biological activity Receptors GABA-A Rats HYDIA Quinolines Pyrazoles Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 31:1738-1745 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00117a012 |
| Popis: | Synthesis and structure-activity relationships of a series of 2-(thien-3-yl)- and 2-(thien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-ones are reported. A number of the compounds possessed 1 order of magnitude higher affinity for the receptors than diazepam. Planarity was one of the structural requirements for binding to benzodiazepine receptors. The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of the pentylenetetrazole-induced convulsions, respectively. Thien-3-yl compounds exhibited inverse agonist activity whereas thien-2-yl analogues with a 5'-alkyl group showed agonist activity. Substitution on the quinoline moiety did not enhance in vivo activity. The most potent compounds were the 5-methylthien-3-yl derivative 6a as an inverse agonist and the 5-methylthien-2-yl compound 13a as an agonist. |
| Databáze: | OpenAIRE |
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