Structure-activity relationship for deacetylation of a homologous series of phenacetin analogs and their N-hydroxy derivatives

GS Estus and JJ Mieyal

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.

Volume 11, Issue 5, pp. 471-476, 09/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics