Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.
1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.
Developmental Research Laboratories, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
T
T
Ohkawa
S
S
Goto
S
S
Miki
A
A
Sato
T
T
Kuroda
K
K
Iwatani
M
M
Takeuchi
M
M
Nakano
D000818:Animals; D019380:Anti-HIV Agents; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
D019380:Anti-HIV Agents; D007093:Imidazoles; C113604:S 1153