Structure-activity relationship for deacetylation of a homologous series of phenacetin analogs and their N-hydroxy derivatives.
Deacetylation of a homologous series of alkoxy acetanilides (p-methoxy-, p-ethoxy- (phenacetin), p-(n)-propoxy- and p-(n)-butoxyacetanilide) and three of the corresponding N-hydroxy derivatives was examined in microsomal fractions from the livers and kidneys of C57BL/6J mice. The rates of deacetylation of the phenacetin analogs to the corresponding amines were found to increase with increasing alkyl chain length. With the N-hydroxy derivatives, the apparent KM was found to decrease with increasing chain length, while the Vmax was relatively unaffected. Treatment of the microsomes with the esterase inhibitor bis-p-nitrophenylphosphate resulted in quite similar extents of inhibition of the deacetylation of the phenacetin analogs and their N-hydroxy derivatives.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology; D010615:Phenacetin / Q000031:analogs & derivatives* / Q000378:metabolism; D013329:Structure-Activity Relationship
D009596:Nitrophenols; C002887:bis(4-nitrophenyl)phosphate; D010615:Phenacetin