Design and synthesis of 3-phenyltetrahydronaphthalenic derivatives as new selective MT2 melatoninergic ligands. Part II |
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Authors: | Sophie Durieux Angéline Chanu Christophe Bochu Valérie Audinot Sophie Coumailleau Jean A Boutin Philippe Delagrange Daniel H Caignard Caroline Bennejean Pierre Renard Daniel Lesieur Pascal Berthelot Saïd Yous |
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Institution: | 1. Laboratoire de Chimie Thérapeutique (EA 1043), Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France;2. Laboratoire d’Application de Résonance Magnétique Nucléaire, Université Lille Nord de France, Faculté des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France;3. Division de Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France;4. Département des Sciences Expérimentales, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France |
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Abstract: | Following our studies of the melatoninergic receptors, we have developed new tetrahydronaphthalenic derivatives of melatonin that have been tested as selective melatonin receptors ligands. Regarding the role of the phenyl substituent to obtain selective ligands, modulation of selectivity and activity have been achieved by modifications of the acyl group and substitutions on the phenyl ring. Ten of the seventeen evaluated derivatives have MT2 receptor affinity similar to that of melatonin. Moreover, we have achieved remarkable MT2 selectivity over MT1 (selectivity >100) and have been able to further extend the RSA of the tetrahydrophthalenic series. However, the compounds presented here display partial agonist or antagonist behavior instead of full agonist. |
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