Mapping the Melatonin Receptor. 6. Melatonin Agonists and Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]azepino[2,1-a]indoles
| Autor: | Maria Panoussopoulou, Andrew Tsotinis, Li-Kuan Yeh, Rüdiger Faust, Muy-Teck Teh, Robert W. Jones, Peter J. Garratt, Theodora Calogeropoulou, David Sugden |
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| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Journal of Medicinal Chemistry. 43:1050-1061 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm980684+ |
| Popis: | 6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2,1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt1 and MT2 receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2,1-a]indoles (7a−d) showed much higher binding affinities than the parent isoindoles (5a−e), and whereas 7a−c were agonists in the functional assay, 7d and 5a−e were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10a−d) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2,1... |
| Databáze: | OpenAIRE |
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