N-Hydroxylamines as a class of compounds are problematic. The alkyl-N-hydroxylamines tend to be toxic, and many of the hydroxylamines of arylamines and arylamides are carcinogenic.1

Alkyl- and aryl-N-hydroxylamines are readily oxidized to chemically reactive nitroso compounds that are at least as toxic as the parent. They form quasiirreversible inhibitors of the enzyme that produces them,126 through generation of tightly bound heme Fe2 + complexes characterized by an ultraviolet spectrum with an absorbance maximum at around 455 nm, analogous to the MI complexes generated from methylenedioxy substrates. The phenomenon is general, and encompasses many widely used drugs,127 including major antibiotics such as troleandomycin and erythromycin,128-130 thereby raising its potential as a source of drug-drug interactions.

N-Hydroxylation is not restricted to amines or amides. Other nitrogen-based functional groups that have at least one N-H bond are susceptible to cytochrome P450-catalyzed N-hydroxylation. Examples include the amidino group of the antiprotozoal drug pentamidine (86)131 (eqn [31]), the guanidino group of the antihypertensive debrisoquine (88)132 (eqn [32]), or the iminoguanidino group of the antihypertensive gaunabenz (90)133 (eqn [33]).

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