Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes
Autor: | Robert Louis Hoffman, Stjernlöf P, Lars O. Hansson, Håkan Wikström, Arvid Carlsson, Ennis, Kjell A. Svensson, Nabil B. Ghazal, M. W. Smith, S. Sundell |
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Rok vydání: | 1995 |
Předmět: |
Male
Agonist Indoles Tertiary amine Stereochemistry medicine.drug_class Biological Availability CHO Cells Binding Competitive Chemical synthesis Receptors Dopamine Rats Sprague-Dawley Structure-Activity Relationship Cricetinae Drug Discovery medicine Animals Structure–activity relationship Receptor Indole test Bicyclic molecule Chemistry Rats Dopamine receptor Receptors Serotonin Molecular Medicine |
Zdroj: | Journal of Medicinal Chemistry. 38:2202-2216 |
ISSN: | 1520-4804 0022-2623 |
Popis: | A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors. |
Databáze: | OpenAIRE |
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