The Metabolism of 5,7-Dinitroindazole in the Mouse and the Rat

Abstract

1. 5,7-Dinitroindazole was extensively metabolized in both rats and mice. The principal biotransformations were nitro group reduction and aromatic hydroxylation.

2. Selective reduction of the 7-nitro group to yield the 7-amino derivative occurred in both species in vivo. The same specificity of reduction was evident when dinitroindazole was incubated with a mixed culture of rat faecal microorganisms.

3. A species difference in conjugation was found. In the mouse the major urinary excretion product was the N-glucuronide of the 7-amino derivative but this was not found in rat urine, acetylation of the 7-amino group being the preferred biosynthetic reaction.

4. This 7-acetamido derivative is the probable precursor of two other metabolites in the rat. One of these has been identified as 3-hydroxy-5-nitro-7-acetamidoindazole and the other may be an N-hydroxylated derivative.