Quinone bioactivation pathways

An example of this overall approach in elucidating novel bioactivation pathways is highlighted with studies on the potassium channel opener, maxipost (BMS-204352) (Figure 6.2), which undergoes a unique P450-mediated bioactivation reaction in rats, dogs, and humans to yield an electrophilic o-quinone-methide intermediate, which covalently binds to albumin in vivo in animals and human.33-34 Acidic hydrolysis of plasma collected after intravenous administration of [14C]-BMS-204352 to rats and human led to the characterization of a... 

SCHEME 1 Bioactivation pathways leading to quinone formation. 

Besides participating in quinone-imine formation, primary anilines can also undergo an alternate CYP- or peroxidase-catalyzed bioactivation pathway that involves an initial Y-hydroxylation on the aniline nitrogen to afford the Y-hydroxylamine metabolite followed by further oxidation to a reactive nitroso species, which, in some cases, can be trapped with GSH (Scheme 10)... 

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