Structure-activity relationship for deacetylation of a homologous series of phenacetin analogs and their N-hydroxy derivatives
Estus, G.S.; Mieyal, J.J.
Drug Metabolism and Disposition the Biological Fate of Chemicals 11(5): 471-476
1983
ISSN/ISBN: 0090-9556 PMID: 6138233 Document Number: 202447
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.