Examination of the D2/5-HT2 affinity ratios of resolved 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: an enantioselective approach toward the design of potential atypical antipsychotics
| Autor: | J. W. Ferkany, L. S. Silverman, Bailey Ma, Carol Tiffany, M E Abreu, Carl Kaiser, Karbon Ew, Richard Eric Mewshaw, Mathew Rm |
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| Rok vydání: | 1993 |
| Předmět: |
Indole test
chemistry.chemical_classification Indoles Bicyclic molecule Receptors Dopamine D2 Stereochemistry Absolute configuration Benzisoxazole Stereoisomerism Crystallography X-Ray chemistry.chemical_compound Polycyclic compound chemistry Drug Design Receptors Serotonin Drug Discovery Molecular Medicine Moiety Enantiomer Chromatography High Pressure Liquid Antipsychotic Agents |
| Zdroj: | Journal of Medicinal Chemistry. 36:3073-3076 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00073a005 |
| Popis: | Enantiomers of several N-substituted 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles were obtained by the resolution of 2-fluoro-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole and 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole followed by N-alkylation. These, as well as the racemates, were evaluated for their affinity for the 5-HT2 and D2 receptors. Those compounds possessing the 7S,10R stereochemistry were consistently recognized by the 5-HT2 and D2 receptors as the eutomer. 2-Fluoro-11-[4-(4-fluorophenyl)-4-oxobutyl]-5,6,7,8,9,10-hexahydro-7S,10 R- iminocyclohept[b]indole [(7S,10R)-8] had the highest affinity for the 5-HT2 receptor (Ki = 0.80 nM), while its distomer (7R,10S)-8 was the most selective member of this class of bridged gamma-carbolines (D2/5-HT2 = 562). Incorporation of a benzoyl or isosteric benzisoxazole moiety tethered by a four-carbon spacer to a bridged gamma-carboline nucleus, possessing the 7S,10R absolute configuration, produced high affinity ligands for the 5-HT2 and D2 receptors. |
| Databáze: | OpenAIRE |
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