The endocannabinoid system dual-target ligand N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide improves disease severity in a mouse model of multiple sclerosis.

The endocannabinoid system dual-target ligand N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide improves disease severity in a mouse model of multiple sclerosis. Eur J Med Chem. 2020 Sep 28;208:112858 Authors: Arena C, Gado F, Di Cesare Mannelli L, Cervetto C, Carpi S, Reynoso-Moreno I, Polini B, Vallini E, Chicca S, Lucarini E, Bertini S, D'Andrea F, Digiacomo M, Poli G, Tuccinardi T, Macchia M, Gertsch J, Marcoli M, Nieri P, Ghelardini C, Chicca A, Manera C Abstract Multiple sclerosis is a chronic inflammatory demyelinating disorder of the central nervous system that eventually leads to progressive neurodegeneration and disability. Recent findings highlighted the emerging role of each target of the endocannabinoid system in controlling the symptoms and disease progression of multiple sclerosis. Therefore, multi-target modulators of the endocannabinoid system could provide a more effective pharmacological strategy as compared to the single target modulation. In this work, N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide (B2) was identified as the most promising compound with dual agonism at cannabinoid receptors type-1 and cannabinoid receptors type-2 and good drug-like properties. In in vitro assays, B2 reduced glutamate release from rat synaptosomes through interaction with cannabinoid receptors type-1 and modulated the production of the pro- and a...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research