Metabolism of 7-fluoro-6-(3,4,5,6-tetrahydrophthalimido)-4- (2-propynyl)-2H-1,4-benzoxazin-3(4H)-one (S-53482) in rat. 1. Identification of a sulfonic acid type conjugate.
To examine the metabolic fate of 7-fluoro-6-(3,4,5, 6-tetrahydrophthalimido)-4-(2-propynyl)-2H-1,4-benzoxazin-3( 4H)-one (S-53482), rats were given a single oral dose of [phenyl-(14)C]-S-53482 at 1 (low) or 100 (high) mg/kg. The radiocarbon was almost completely eliminated within 7 days after administration in both groups. (14)C recoveries (expressed as percentages relative to the dosed (14)C) in feces and urine were 56-72 and 31-43%, respectively, for the low dose and 78-85 and 13-23%, respectively, for the high dose. S-53482 and seven metabolites were identified in urine and feces. Six of them were purified by several chromatographic techniques and identified by spectroanalyses (NMR and MS). Alcohol derivatives and an acetoanilide derivative were isolated from urine. Three sulfonic acid conjugates having a sulfonic acid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthalimide moiety were isolated from feces. On the basis of the metabolites identified in this study, the metabolic pathways of S-53482 in rats are proposed.
Tomigahara
Y
Y
Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554, Japan.
Matsui
M
M
Matsunaga
H
H
Isobe
N
N
Kaneko
H
H
Nakatsuka
I
I
Yoshitake
A
A
Yamane
S
S
D000818:Animals; D048588:Benzoxazines; D005260:Female; D006540:Herbicides / Q000378:metabolism*; D008297:Male; D010078:Oxazines / Q000378:metabolism*; D010797:Phthalimides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013451:Sulfonic Acids / Q000378:metabolism
D048588:Benzoxazines; D006540:Herbicides; D010078:Oxazines; D010797:Phthalimides; D013451:Sulfonic Acids; C106487:flumioxazin