%0 Journal Article
%A Murineddu, Gabriele
%A Deligia, Francesco
%A Ragusa, Giulio
%A García Toscano, Laura
%A Gómez Cañas, María
%A Asproni, Battistina
%A Satta, Valentina
%A Cichero, Elena
%A Pazos, Ruth
%A Fossa, Paola
%A Loriga, Giovanni
%A Fernández Ruiz, José Javier
%A Pinna, Gerard A.
%T Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists
%D 2018
%@ 0968-0896
%U https://hdl.handle.net/20.500.14352/131205
%X A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB1 receptors (Ki values of 44.6 nM for CB1 receptors and >40 μM for CB2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB1 receptors with Ki values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB1 receptor in the [35S]-GTPγS binding assays, and none showed adequate predictive blood–brain barrier permeation, exhibiting low estimated LD50. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist.
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