Medicinal azides. Part 8. The in vitro metabolism of p-substituted phenyl azides

Abstract

1. A series of p-substituted aromatic azides was synthesized and their metabolism investigated in suspensions of mouse liver microsomes and mouse hepatocytes. Metabolite analysis was performed by h.p.l.c. 2. On incubation with microsomes under anaerobic conditions p-nitro, p-cyano- and p-chlorophenyl azide afforded metabolites which co-chromatographed with the respective aromatic amines. The rate at which p-nitrophenyl azide was metabolically reduced was approximately 20-fold that observed for p-cyano- and p-chlorophenyl azide. 3. Phenyl azide, p-methoxyphenyl azide and the aliphatic congener, phenethyl azide, did not furnish detectable amounts of metabolites on incubation with microsomes under anaerobic conditions. When phenyl azide and p-methoxyphenyl azide were incubated with hepatocytes or microsomes under aerobic conditions the resulting chromatograms furnished peaks which co-eluted with authentic p-hydroxyphenyl azide. 4. The microsomal reduction of p-nitrophenyl azide was dependent upon the presence of viable microsomes and NADPH, and on the absence of oxygen above the incubation medium.