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Novel conformationally constrained analogues of agomelatine as new melatoninergic ligands
Marouan Rami1, Elodie Landagaray, Mohamed Ettaoussi
1University of Lille Nord de France, F-59000 Lille, France. marouanr@yahoo.fr
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.
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