In vitro studies on the metabolism of dibenzo[c,f]-[1,2]diazepine

Abstract

Dibenzo [c,f]-[1,2] diazepine is a new compound with a tricyclic structure and a double bond between two nitrogen atoms in positions 1 and 2 of the molecule. Its in vitro metabolism has been studied, incubating the compound with rat liver microsomes. Two metabolites have been identified: dibenzo [c,f] - [1,2]diazepine-1-N-oxide and a monohydroxyderivative in the aromatic ring.

In vivo studies on the metabolism of dibenzo [c,f]-[1,2] diazepine

“…This mass spectrum suggested for this compound the structure of a dibenzo [c,f]- [ 1,2] diazepine-Ll-one, which was confirmed by comparison with an authentic sample of dibenzo [c,f]- [1,2] diazepine-l lone (III), which had the same GLC retention time, the same TLC Rf and the same mass spectrum as the metabolic product. The spot with Rf 0.33, analyzed as above, proved to be the l l-hydroxy-derivative of I (IV); in fact, during GLC, it gave only a weak peak, whereas the methyl derivative with trimethylanilinium hydroxide gave an intense peak with a shorter retention time (Figure 2 The spot with Rf 0.24, analyzed by DIS, gave the mass spectrum reported in Figure 7.…”

“…The molecular ion, which is also the base peak, at m/e 212, has 18 mass units more than the parent compound. Loss of a hydrogen atom gives the ion 211; both the ions 212 and 211 lose an oxygen atom to give the peaks ions at m/e 196 and 195 respectively; the presence of the ions at m/ e 165 and 152 suggests, for this compound, the structure of a dibenzo [c,f]- [ 1,2] diazepine-l-Nhydroxy-derivative (V), which was confirmed by the flash methylation reaction, giving the corresponding methylated derivative (Figure 2, XI).…”

“…The in vitro metabolic biotransformation of dibenzo [c,f]- [1,2] diazepine (I) has already been studied and described (1). The present study concerns the in vivo biotransformation of I after i.p.…”