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)-butoxy-acetanilide) 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 K(M) was found to decrease with increasing chain length, while the V(max) 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.