Regioselectivity and reactivity in microsomal hydroxylation of a series of N-acyl- and N-sulfonylamines in rats.
Regioselectivity and overall reactivity in the hydroxylation of a series of substituted N-benzoyl- and benzenesulfonyl aliphatic and alicyclic amines with rat liver microsomes were investigated. The hydroxylation occurred predominantly at the position gamma to the nitrogen atom. para-Alkyl-substituted benzoylamines were hydroxylated at both the benzylic positions as well as the gamma-position, whereas para-substituted benzenesulfonylamines were hydroxylated mainly at the benzylic position. The relative overall reactivity of primary, secondary, and tertiary carbon atoms was about 1:3:8, and the contribution of substituents adjoining to the reaction site was negligible. Benzylic hydroxylation proceeded stereoselectively, whereas gamma-hydroxylation gave optically inactive metabolites; the inter- and intramolecular isotope effects in the hydroxylation were 1.6 and 7.2, respectively.
D000818:Animals; D001190:Arylsulfonates / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000378:metabolism*
D001190:Arylsulfonates; D013449:Sulfonamides