抄録
Five kinds of N-substituted 3-hydroxy-2-methyl-4(1H)-pyridinones, and three kinds of 1-hydroxy-2(1H)-pyrimidinones were synthesized. Treatment of 3-hydroxy-4(1H)-pyridinones with VO(acac)2 in CH3OH exclusively gave CH3O-coordinated oxovanadium (V) complexes. On the other hand, treatment with VOSO4 in H2O at pH 10 for 3-hydroxy-4(1H)-pyridinones and at pH 7 for 1-hydroxy-2(1H)-pyrimidinones afforded the corresponding oxovanadium (IV) complexes. These complexes were fully characterized by means of IR, UV-vis, 1H-and 51V-NMR, FAB-MS, ESR spectroscopies, and combustion analysis. From the result of the inhibitory effect of oxovanadium (IV) complexes on free fatty acid (FFA) release from rat adipocytes treated with epinephrine in the presence of glucose in vitro, it was revealed that bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)oxovanadium (IV) showed the highest insulin-mimetic activity. Furher, the in vivo insulin-mimetic activity was evaluated with streptozotocin (STZ)-induced diabetic rats. Blood glucose levels were substantially lowered from hyperglycemic to nomal levels after the treatment with bis (1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato) oxovanadium (IV) by daily intraperitoneal injections.
