Oxidation of Polycyclic N -Arylacetamides to Glycol-amides and Hydroxamic Acids in Rabbits

Abstract

1. After administration to rabbits of N(2-fluorenyl)acetamide, N(4-biphenylyl)-acetamide, N(2-phenanthryl)acetamide, or N(3-phenanthryl)acetamide, the corresponding glycolamides and the N-hydroxy derivatives of the acetamides were isolated from urine and identified by u.v., i.r. or n.m.r. spectra. The glycolamides amounted to less than 1% of the dose of the corresponding acetamides. The proportion of N-hydroxy derivatives was always much higher.

2. The N-hydroxy metabolite of N(4-cyclohexylphenyl)acetamide also was isolated from urine, but the corresponding glycolamide was not unequivocally identified.

3.The N-Hydroxy derivatives or glycolamides were not found in urine after administration of N(3-biphenylyl)acetamide, N(2-naphthyl)acetamide, or N(2-anthryl)acetamide.

4. About 5% of a dose of N(4-sulphamoylphenyl)acetamide was found in rabbits urine as the corresponding glycolamide and another 3% as a product of its further oxidation, namely, N(4-sulphamoylphenyl)oxamic acid.

5. Following intraperitoneal injection of N(2-fluorenyl)glycolamide less than 1% of the dose was found unchanged in urine, but much larger proportions were recovered as N(2-fluorenyl)oxamic acid. N-hydroxy-N(4-chlorophenyl)aceta-amide and N-hydroxy-N(3-biphenylyl)acetamide after intraperitoneal injection, were excreted in urine in widely varying amounts.

6. Urinary excretion by rabbits of N-hydroxy-N-arylacetamides and N-arylglycolamides does not indicate the true extent of transformation of the parent N-arylacetamides into these metabolites.