Synthesis and evaluation of N-(phenylalkyl)acetohydroxamic acids as potential substrates for N-arylhydroxamic acid N,O-acyltransferase.

N-(4-Phenylcyclohexyl)acetohydroxamic acid and a series of N-(phenylalkyl)acetohydroxamic acids were synthesized and evaluated as substrates for partially purified rat and hamster hepatic arylhydroxamic acid N,O-acyltransferase systems (AHAT). The compounds were assayed for their abilities to function as acetyl donors in the AHAT-mediated transacetylation of 4-aminoazobenzene and for their abilities to participate in the AHAT-mediated conversion of N-arylhydroxylamines to electrophilic intermediates that form methylthio adducts upon reaction with N-acetylmethionine. None of the newly synthesized compounds displayed significant activity in either of the assays. The results of this study indicate that acetohydroxamic acids that have the nitrogen atom of the hydroxamic acid group attached directly to aliphatic or cycloalkyl groups are not likely to serve as substrates or inhibitors of AHAT.