1,2-Dihydro-2-oxopyridine-3-carboxamides: the C-5 substituent is responsible for functionality switch at CB2 cannabinoid receptor.

The relevance of CB2R-mediated therapeutic effects is well-known for the treatment of inflammatory and neuropathic pain and neurodegenerative disorders. In our search for new cannabinoid receptor modulators, we report the optimization of a series of 1,2-dihydro-2-oxopyridine-3-carboxamide derivatives as CB2R ligands. In particular, N-cycloheptyl-5-(4-methoxyphenyl)-1-(4-fluorobenzyl)-pyridin-2(1H)-on-3-carboxamide (17) showed high CB2R affinity (K(i) = 1.0 nM), accompanied by interesting K(i)(CB1R)/K(i)(CB2R) selectivity ratio (SI = 43.4). Compound 17 was also identified as a potent CB2R neutral antagonist/weak partial inverse agonist. Finally we found that the functionality activity of the series of 1,2-dihydro-2-oxopyridine is controlled by the presence of a substituent in position 5 of the heterocyclic nucleus. In fact when the hydrogen atom in position 5 of the unsubstituted compound 1 was replaced with a phenyl group (compound 18) the CB2R activity was shifted from agonism to inverse agonism whereas the introduction in the same position of p-methoxyphenyl group lead to compound 17 which showed a behavior as CB2R neutral antagonist/weak partial inverse agonist.

Determination of water-soluble vitamins in multivitamin dietary supplements and in artichokes by micellar electrokinetic chromatography.

Several procedures of extraction with solvents for the simultaneous determination of vitamin C and some vitamins belonging to the B group (thiamine, riboflavine, nicotinic acid and nicotinamide) in multivitamin preparations and in artichokes (Cynara cardunculus subsp. scolymus [L.] Hegi) were developed. Different experimental conditions were used, in terms of heat treatment, composition and pH of the extraction mixture, with particular attention to high-temperature steps; purification of the extracts with solid phase extraction and stabilisation through lyophilisation were discussed. Analyses of the extracts were conducted by capillary electrophoresis in micellar electrokinetic chromatography modality. Borate buffer at pH 8.2 was used, and sodium dodecyl sulphate was added to the background electrolyte as surfactant. A range of linearity was determined and calibration curves were plotted for all the analytes.