%0 Journal Article
%A Ragusa, Giulio
%A Gómez Cañas, María
%A Morales, Paula
%A Pazos, María 
%A Rodríguez Cueto, Carmen Aurora
%A Asproni, Battistina
%A Cichero, Elena
%A Fossa, Paola
%A Pinna, Gerard 
%A Jagerovic, Nadine
%A Fernández Ruiz, José Javier
%A Murineddu, Gabriele
%T New pyridazinone-4-carboxamides as new cannabinoid receptor type-2 inverse agonists: Synthesis, pharmacological data and molecular docking
%D 2017
%@ 0223-5234
%U https://hdl.handle.net/20.500.14352/93394
%X In the last few years, cannabinoid type-2 receptor (CB2R) selective ligands have shown a great potential as novel therapeutic drugs in several diseases. With the aim of discovering new selective cannabinoid ligands, a series of pyridazinone-4-carboxamides was designed and synthesized, and the new derivatives tested for their affinity toward the hCB1R and hCB2R. The 6-(4-chloro-3-methylphenyl)-2-(4-fluorobenzyl)-N-(cis-4-methylcyclohexyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (9) displayed high CB2-affinity (KiCB2 = 2.0 ± 0.81 nM) and a notable selectivity (KiCB1/KiCB2 > 2000). In addition, 9 and other active new synthesized entities have demonstrated to behave as CB2R inverse agonists in [35S]-GTPγS binding assay. ADME predictions of the newly synthesized CB2R ligands suggest a favourable pharmacokinetic profile. Docking studies disclosed the specific pattern of interactions of these derivatives. Our results support that pyridazinone-4-carboxamides represent a new promising scaffold for the development of potent and selective CB2R ligands.
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