Inhibitors of hepatic mixed function oxidase. 3. Inhibition of hepatic microsomal aniline hydroxylase and aminopyrine demethylase by 2,6- and 2,4-dihydroxyphenyl alkyl ketones and related compounds.

A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-dihydroxyacetophenone (27). In the 2,6 series activity against both microsomal systems varied only over a relatively narrow range, 6-allyloxy-2-hydroxyacetophenone (19) being the most potent inhibitor. In the 2,4 series, activity against aniline hydroxylase was poor or absent in most cases. tthe most potent inhibitor was 5-ethyl-2,4-dihydroxyacetophenone (31). In contrast, high activity against aminopyrine demethylase was frequently displayed in this series, 3,5-dibromo-2,4-dihydroxypropiophenone (36) showing greatest inhibitory potency. The effects of some compounds on hexobarbital sleeping times and zoxazolamine paralysis times in mice were also examined.