Mechanism of the microsomal N-hydroxylation of para-substituted benzamidines.
With the aid of HPLC analyses and simple Michaelis-Menten kinetics, the maximum rates of the microsomal N-oxygenation of various para-substituted benzamidines 1 to benzamidoximes 2 were determined. The presence of electron-donating substituents increased the rates whereas the presence of electron-accepting substituents decreased them. A significant correlation between the logarithm of the maximum rates with the Hammett sigma p constants was found for a reaction constant of rho = -0.88. These results support the postulated radical mechanism for the N-oxygenation by the cytochrome P-450 enzyme system.
Clement
B
B
Pharmazeutisches Institut, Albert-Ludwigs-Universität, Freiburg, Federal Republic of Germany.
Zimmermann
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M
D000578:Amidines / Q000378:metabolism*; D000818:Animals; D001550:Benzamidines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D011817:Rabbits; D013329:Structure-Activity Relationship
D000578:Amidines; D001550:Benzamidines; D003577:Cytochrome P-450 Enzyme System