Abstract
Biotransformation of N-(2-mercapto-2-methylpropanoyl)-L-cysteine (SA96), a dithiol compound developed as an anti-rheumatic, was studied in rats by oral administration. The two S-methylated compounds were isolated from urinary extract by chromatographic methods. By their nuclear magnetic resonance spectra and by comparison with authentic samples, they were identified as N-[2-methyl-2-(methylthio) propanoyl]-L-cysteine (SA679 : S-methylated compound at 2-mercapto-2-methylpropanoic acid moiety of SA96) and as S-methyl-N-[2-methyl-2-(methylthio) propanoyl]-L-cysteine (SA672 : S-methylated compound at both mercapto groups of SA96). However, it was demonstrated that N-(2-mercapto-2-methylpropanoyl)-S-methyl-L-cysteine (SA680), a compound S-methylated only at cysteine moiety of SA96, was absent in the urine. Additionally, (4R)-7, 7-dimethyl-6-oxo-tetrahydro-3H-1, 2, 5-dithiazepine-4-carboxylic acid (SA981 : intramolecular disulfide of SA96), was also detected in the blood and urine. On the basis of these results, the characteristics of metabolic fate of SA96 were discussed.
