Bivalent ligand approach on N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide : synthesis, binding affinity and intrinsic activity for MT1 and MT2 melatonin receptors
Articolo
Data di Pubblicazione:
2011
Citazione:
Bivalent ligand approach on N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide : synthesis, binding affinity and intrinsic activity for MT1 and MT2 melatonin receptors / G. Spadoni, A. Bedini, P. Orlando, S. Lucarini, G. Tarzia, M. Mor, S. Rivara, V. Lucini, M. Pannacci, F. Scaglione. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 19:16(2011), pp. 4910-4916.
Abstract:
We report the synthesis, binding properties and intrinsic activity at MT1 and MT2 melatonin receptors of new dimeric melatonin receptor ligands in which two units of the monomeric agonist N-{2-[(3-methoxyphenyl)
methylamino]ethyl}acetamide (1) are linked together through different anchor points. Dimerization of compound 1 through the methoxy substituent leads to a substantial improvement in selectivity for the MT1 receptor, and to a partial agonist behavior. Compound 3a, with a trimethylene linker, was
the most selective for the MT1 subtype (112-fold selectivity) and compound 3d, characterized by a hexamethylene spacer, had the highest MT1 binding affinity (pKiMT1 = 8.47) and 54-fold MT1-selectivity.
Dimerization through the aniline nitrogen of 1 abolished MT1 selectivity, leading to compounds with either a full agonist or an antagonist behavior depending on the nature of the linker.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Bivalent ligand; Melatonin; Melatoninergic dimers; MT 1 and MT 2 receptors
Elenco autori:
G. Spadoni, A. Bedini, P. Orlando, S. Lucarini, G. Tarzia, M. Mor, S. Rivara, V. Lucini, M. Pannacci, F. Scaglione
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