Structure determination of metabolites of rilmazafone, a 1H-1,2,4-triazolyl benzophenone derivative in monkey urine.
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-tr iaz ole-3-carboxamide hydrochloride dihydrate (rilmazafone hydrochloride) was studies 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 hydrolysed to M-4, or hydroxylated at the 4-position of benzodiazepine ring or the p-position of the o-chlorophenyl group.
Koike
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Norikura
R
R
Iwatani
K
K
Sugeno
K
K
Takahashi
S
S
Nakagawa
Y
Y
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003500:Cyclization; D005260:Female; D006900:Hydroxylation; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D008252:Macaca fascicularis; D013058:Mass Spectrometry; D008968:Molecular Conformation; D014230:Triazoles / Q000652:urine*
D006993:Hypnotics and Sedatives; D014230:Triazoles; C041075:rilmazafone