Design and synthesis of new N1 and C3-substituted 4-fluoroindolic melatoninergics
| Autor: | Andrew Tsotinis, Andreas Eleutheriades, Kathryn Davidson, David Sugden |
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| Rok vydání: | 2007 |
| Předmět: |
Indoles
Stereochemistry Population Xenopus Melanophores Plasma protein binding Biology Melatonin receptor 3T3 cells Mass Spectrometry law.invention Iodine Radioisotopes Mice Radioligand Assay Xenopus laevis law Drug Discovery medicine Animals Humans Transition Temperature Receptor education Melatonin education.field_of_study Chromatography Molecular Structure Receptor Melatonin MT2 Receptor Melatonin MT1 biology.organism_classification Tryptamines Pigment granule medicine.anatomical_structure Indenes Drug Design Recombinant DNA NIH 3T3 Cells Protein Binding |
| Zdroj: | Current drug discovery technologies. 4(3) |
| ISSN: | 1570-1638 |
| Popis: | A series of new C-3 and N1-substituted 4-fluorotryptamides have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and bind to the recombinant human MT(1) and MT(2) melatonin receptor subtypes expressed in NIH 3T3 cells. Planar sp(2) geometry at C-3-betaC seems to decrease the population of the preferred conformation as it renders 4-fluoroindoles 4b-d weaker antagonists than their C-3-betaC-unsubstituted congeners 3a-e. This effect is not preclusively linked with the C-3 region, as the same geometry around N1 (compounds 5a-c) similarly leads to weak antagonistic action. Last, the new C-3 substituted 4-fluorotryptamides presented herein are substantially more potent than their respective N-OMe functionalized congeners, previously reported. |
| Databáze: | OpenAIRE |
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