Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands

Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT(1) and MT(2) melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compoun...

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Detalles Bibliográficos
Autores principales: Rami, Marouan, Landagaray, Elodie, Ettaoussi, Mohamed, Boukhalfa, Koussayla, Caignard, Daniel-Henri, Delagrange, Philippe, Berthelot, Pascal, Yous, Saïd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269769/
https://www.ncbi.nlm.nih.gov/pubmed/23262445
http://dx.doi.org/10.3390/molecules18010154
Descripción
Sumario:Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT(1) and MT(2) 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 MT(1). Compounds 7a and 7b exhibiting nanomolar affinity towards the MT(2) receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT(2)-selectivity.

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