Mechanism of antioxidative activity of fluvastatin-determination of the active position.
In order to clarify the mechanism of action for the antioxidative activity of fluvastatin sodium (FLV, (+/-)-sodium (3RS, 5RS, 6E)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3, 5-dihydroxy-6-heptanoate) and its derivatives, reaction of the corresponding methyl ester of FLV with di-tert-butyl diperoxyoxalate was examined, and the corresponding keto derivative was isolated from the reaction mixture. On the basis of this result, it was concluded that the active site is the allylic carbon conjugated with the indole ring.
Nakamura
T
T
Analytical Chemistry Department, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Nishi
H
H
Kokusenya
Y
Y
Hirota
K
K
Miura
Y
Y
D000924:Anticholesteremic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002853:Chromatography, Liquid; D003497:Cyclic N-Oxides; D004952:Esters / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D000077340:Fluvastatin; D005609:Free Radicals; D006859:Hydrogen / Q000737:chemistry; D007202:Indicators and Reagents; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D013113:Spin Labels; D019097:Spin Trapping
D000924:Anticholesteremic Agents; D000975:Antioxidants; D003497:Cyclic N-Oxides; D004952:Esters; D005229:Fatty Acids, Monounsaturated; D005609:Free Radicals; D007202:Indicators and Reagents; D007211:Indoles; D013113:Spin Labels; D000077340:Fluvastatin; D006859:Hydrogen; C003959:TEMPO