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Molecules 2013, 18(1), 154-166; doi:10.3390/molecules18010154
Article

Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands

1,2,* , 1,2, 1,2, 1,2, 3, 3, 1,2 and 1,2
1 University of Lille Nord de France, F-59000 Lille, France 2 UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France 3 Sciences Expérimentales, Institut de Recherches Servier, 92150 Suresnes, France
* Author to whom correspondence should be addressed.
Received: 29 October 2012 / Revised: 14 December 2012 / Accepted: 18 December 2012 / Published: 24 December 2012
(This article belongs to the Section Medicinal Chemistry)
Download PDF [226 KB, 18 June 2014; original version 18 June 2014]

Abstract

Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT1 and MT2 melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compound 5), oxazolidinone (compound 7a), pyrrolidinone (compound 7b), imidazolidinedione (compound 12), thiazole (compounds 13 and 14) and isoxazole moieties (compound 15) led to a decrease of the melatoninergic binding affinities, particularly at MT1. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT2 receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT2-selectivity.
Keywords: agomelatine; agonist; conformationally restriction; melatonin agomelatine; agonist; conformationally restriction; melatonin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Rami, M.; Landagaray, E.; Ettaoussi, M.; Boukhalfa, K.; Caignard, D.-H.; Delagrange, P.; Berthelot, P.; Yous, S. Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands. Molecules 2013, 18, 154-166.

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