Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: An investigation of the 1,8-naphthyridin-2(1H)-one scaffold

Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis

“…In general terms, however, CB1 and CB2 receptor agonists have been found to have inhibitory effects on tumor cell growth, whereas antagonists and inverse agonists have been found to have stimulatory effects (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Moreover, clinical studies have shown that cannabinoid receptor agonists exert analgesic and muscle relaxant properties in patients with metastatic pain (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) Most recent interest has been focused on the potential role of CB2-selective agonists in the treatment of malignant disease, because these agents (a) lack of adverse psychotropic effects that are associated with CB1-selective ligands (19), (b) exert anti-proliferative effects on different cancer cell lines (20,21), (c) inhibit cancer-induced osteolysis and fractures (22), and (d) reduce bone pain in various preclinical models (22,23). At the present time CB2 agonists are considered to exert these effects by inhibiting tumor cell growth and by suppressing the release of cytokines and chemokines from cancer cells (24).…”

Effects on Immune Cells of a New 1,8-Naphthyridin-2-One Derivative and Its Analogues as Selective CB2 Agonists: Implications in Multiple Sclerosis

“…In this study, we assessed the immune-modulatory effects of novel described CB2 selective agonists, 1,8-naphthyridine, pyridine and quinoline derivatives [23], [24], [27]. In particular, we compared the effects of these compounds in lymphocytes isolated from both MS patients and healthy donors.…”

“…1,8-naphthyridin-2-one derivative: N -(4-methylcyclohexyl)-1-benzyl-1,8-naphthyridin-2(1 H )-on-3-carboxamide (CB74), [24] quinolin-2-one derivative: N -cyclohepthyl-1-(2-morpholin-4-ylethyl)-quinolin-2(1 H )-on-3-carboxamide (VL23); [27] pyridine-2-one derivative: N -cyclohepthyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide (AF4) [27]. Drugs and SR144528 were dissolved in DMSO.…”

“…In macrophages/microglia, CB2 receptor stimulation suppressed the release of pro-inflammatory factors [20], [21] and some studies suggest the potential immunosuppressive role of CB2 selective ligands [22]. Recently, novel CB2 receptor agonists, 1,8-naphthyridine, pyridine and quinoline derivatives [23], [24], [25], [26], [27] have been designed with high CB2 affinity and CB2 versus CB1 selectivity in agreement with molecular modeling studies [23]. Some of these compounds exhibited pharmacological properties like inhibitory action on immunological human basophil activation mediated by the CB2 receptor [23], [24].…”

A convenient approach to the synthesis of substituted 2-(methylamino)quinoline-3-carboxamides

“…Крім цього, ці спо-луки є потенційними інгібіторами β-секретази (BACE) [13], ацетилхолінестерази [14], тирозин-кінази [15], а також агоністами каннабіноїдних рецепторів СВ1 та СВ2 [16][17][18][19].…”