Structure-activity relationships in the formation of amides from substituted N-benzylanilines

1. The in vitro hepatic microsomal metabolism of certain substituted N-benzylanilines was studied in the male hamster to establish the mechanism(s) and process(es) involved in the formation of the corresponding amides.2. N-Benzyl-2,4,6-trihalogeno, N-benzyl-4-cyano- and N-benzyl-4-nitroanilines were only metabolized by N-debenzylation. However, N-benzyl-4-methyl- and N-benzyl-2,4,6-trimethylanilines gave rise to both the corresponding amide and nitrone metabolites together with dealkylation products. These latter two substrates also produced hydroxymethyl metabolites as major products. Metabolism of N-(2,4,6,-trimethylbenzyl)aniline also led to the formation of an amide metabolite. The dealkylation products, the corresponding imine and an unknown metabolite, probably an hydroxylated product were also detected with this substrate.3. N-(2,4-Dichlorobenzyl) and N-(2,6-dichlorobenzyl) anilines yielded the corresponding nitrone metabolites; but no amide metabolite was detected. Oxidative dealkylation leading t...