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 sulfonicacid 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 si ngle oral dose of [phenyl-C-14]-S-53482 at 1 (low) or 100 (high) mg/kg. The radiocarbon was almost completely eliminated within 7 days after administr ation in both groups. C-14 recoveries (expressed as percentages relative to the dosed C-14) in feces and urine were 56-72 and 31-43%, respectively, fo r the low dose and 78-85 and 13-23%, respectively, for the high dose. S-534 82 and seven metabolites were identified in urine and feces. Six of them we re purified by several chromatographic techniques and identified by spectro analyses (NMR and MS). Alcohol derivatives and an acetoanilide derivative w ere isolated from urine. Three sulfonic acid conjugates having a sulfonic a cid group incorporated into the double bond of the 3,4,5,6-tetrahydrophthal imide moiety were isolated from feces. On the basis of the metabolites iden tified in this study, the metabolic pathways of S-53482 in rats are propose d.