Structure determination of metabolites of rilmazafone, a1H-1,2,4-triazolyl benzophenone derivative in monkey urine

Abstract

1. The metabolism of a new hypnotic 5-[(2-aminoacetamido)methyl]-1-[4-chloro-2-(o-chlorobenzoyl)phenyl]-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide hydrochloride dihydrate (rilmazafone hydrochloride) was studied in female cynomolgus monkeys. 2. The structures of ten urinary metabolites were determined by mass spectrometry, and confirmed by comparison with synthetic authentic compounds. 3. Pathways of metabolism are postulated indicating that rilmazafone is desglycylated and cyclized to M-1, demethylated successively to M-2 and M-3, then hydrolyzed to M-4, or hydroxylated at the 4-position of benzodiazepine ring or the p-position of the o-chlorophenyl group.