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oai:docta.ucm.es:20.500.14352/1312052026-01-29T00:54:36Zcom_20.500.14352_14col_20.500.14352_15

Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists Murineddu, Gabriele Deligia, Francesco Ragusa, Giulio García Toscano, Laura Gómez Cañas, María Asproni, Battistina Satta, Valentina Cichero, Elena Pazos, Ruth Fossa, Paola Loriga, Giovanni Fernández Ruiz, José Javier Pinna, Gerard A. Sulfenamides Sulfonamides CB1 antagonism Diarylpyridazines ADMET model Docking studies Farmacología (Medicina) Neurociencias (Medicina) 3209 Farmacología 2490 Neurociencias 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. Depto. de Bioquímica y Biología Molecular Fac. de Medicina TRUE pub 2026-01-28T13:48:06Z 2026-01-28T13:48:06Z 2018-01 journal article VoR https://hdl.handle.net/20.500.14352/131205 0968-0896 10.1016/j.bmc.2017.11.051 eng Murineddu G, Deligia F, Ragusa G, García-Toscano L, Gómez-Cañas M, Asproni B, et al. Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists. Bioorganic & Medicinal Chemistry 2018;26:295–307. https://doi.org/10.1016/j.bmc.2017.11.051 restricted access application/pdf Elsevier