Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3
| Autor: | Saïd Yous, Pierre Renard, Mohamed Ettaoussi, Pascal Berthelot, Marouan Rami, Jean A. Boutin, Daniel-Henri Caignard, Veronique Leclerc, Philippe Delagrange, Amaury Farce |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Binding Sites Molecular Structure Ligand Chemistry Stereochemistry Organic Chemistry Receptors Melatonin Substituent Stereoisomerism General Medicine Naphthalenes Ligands Melatonin receptor Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Drug Design Melatonin binding Drug Discovery Binding site Acyl group Acetamide Melatonin |
| Zdroj: | European Journal of Medicinal Chemistry. 46:1622-1629 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2011.02.010 |
| Popis: | Naphthalenic analogs of MCA-NAT (5-methoxycarbonylamino-N-acetyltryptamine) have been synthesized and evaluated as melatonin receptor ligands. Introduction of a methoxycarbonylamino substituent at the C-7 position of the naphthalenic nucleus yields MT3 selective ligands. This selectivity can be modulated with suitable variations of the C-7 position and the acyl group on the C-1 side chain. We identified new series of compounds with affinity for the MT3 binding site in the nanomolar range, and singled out a selective ligand, (N-[2-(7-methylsulfamoyl-naphth-1-yl)ethyl]acetamide (17), with a Ki of 4.9 nM and selectivity of 1024 and 2040 versus MT1 and MT2 receptors respectively. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect