RT Journal Article
T1 New pyridazinone-4-carboxamides as new cannabinoid receptor type-2 inverse agonists: Synthesis, pharmacological data and molecular docking
A1 Ragusa, Giulio
A1 Gómez Cañas, María
A1 Morales, Paula
A1 Pazos, María
A1 Rodríguez Cueto, Carmen Aurora
A1 Asproni, Battistina
A1 Cichero, Elena
A1 Fossa, Paola
A1 Pinna, Gerard
A1 Jagerovic, Nadine
A1 Fernández Ruiz, José Javier
A1 Murineddu, Gabriele
AB 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.
PB Elsevier
SN 0223-5234
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/93394
UL https://hdl.handle.net/20.500.14352/93394
LA eng
NO Ragusa G, Gómez-Cañas M, Morales P, Rodríguez-Cueto C, Pazos MR, Asproni B, Cichero E, Fossa P, Pinna GA, Jagerovic N, Fernández-Ruiz J, Murineddu G. New pyridazinone-4-carboxamides as new cannabinoid receptor type-2 inverse agonists: Synthesis, pharmacological data and molecular docking. Eur J Med Chem. 2017 Feb 15;127:398-412. doi: 10.1016/j.ejmech.2017.01.002. Epub 2017 Jan 4. PMID: 28088085.
NO Ministerio Economía y competitividad (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 9 abr 2025