Arena, Chiara; Gado, Francesca; Di Cesare Mannelli, Lorenzo; Cervetto, Chiara; Carpi, Sara; Reynoso-Moreno, Ines; Polini, Beatrice; Vallini, Erika; Chicca, Stefano; Lucarini, Elena; Bertini, Simone; D′Andrea, Felicia; Digiacomo, Maria; Poli, Giulio; Tuccinardi, Tiziano; Macchia, Marco; Gertsch, Jurg; Marcoli, Manuela; Nieri, Paola; Ghelardini, Carla; Chicca, Andrea; Manera, Clementina published the artcile< 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>, Safety of 1-Chloropyrrolidine-2,5-dione, the main research area is endocannabinoid modulator preparation multiple sclerosis cannabinoid receptor analgesic; 1,2-Dihydropyridine-2-oxo-3-carboxamides; EAE mouse Model multiple sclerosis; Endocannabinoid system; Glutamate release; Microglial cell; Neuropathic pain.
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 pharmacol. 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 anti-inflammatory cytokines (interleukins IL-1β and IL-6 and interleukin IL-10 resp.) via cannabinoid receptors type-2 activation. Furthermore, B2 demonstrated antinociceptive effects in an animal model of neuropathic pain and efficacy in an exptl. autoimmune encephalomyelitis model of multiple sclerosis.
European Journal of Medicinal Chemistry published new progress about Analgesics. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Safety of 1-Chloropyrrolidine-2,5-dione.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics