Metabolism of Drugs. LXX. Further Study on Antipyrine Metabolism

Abstract

In the previous paper, it was shown that antipyrine was oxidized not only to 4-hydroxyantipyrine, but also to 3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-one which was characterized on the basis of analytical and spectral data. The present study established the latter pathway, the oxidation of methyl group at 3-position of pyrazolinone ring by the chemical synthesis of authentic sample, and also demonstrated chromatographically the subsequent pathway to 2-methyl-1-phenyl-5-oxo-3-pyrazolin-3-carboxylic acid. Possible importance of this serial oxidation steps was discussed concerning with antipyrine allergy problem. By the preliminary test it was shown that 3-hydroxymethyl metabolite did not retain the antipyretic acitivity.