Unusual Biotransformation of a Pyrrolotriazine Heterocycle

Biotransformations can be diverse and not limited to simple oxidation or dealkylation. An oncologic agent, The BMS-690514, is an example of unexpected metabolism. This compound undergoes multiple biotransformations, among them are P450 mediated oxidations of its heterocycle pyrrolotriazine group. Two major metabolites A and B are resulting from + O biotransformation.  However if the metabolite A shows a hydroxylation of the heterocycle, the metabolite B seems to undergone a unusual rearrangement. The isolation of that metabolite demonstrated the formation a hydroxypyridotriazine group.

This structure was confirmed using NMR spectrometry. The metabolism study of deuterium and tritium isotope label at the oxidized position showed that the label was retain during the formation of the metabolite A and lost during the formation of the metabolite B. The authors concluded that this metabolite was formed via epoxidation.

Haizheng Hong et al. Chem. Res. Toxicol. 201124, 125-134.