Identification of canine urinary metabolites of the antiprotozoal agent 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole

Identification of In Vitro (Rat Liver Postmitochondrial S9 Fraction) Metabolites of the Antiprotozoal Agent 3a,4,5,6,7,7a-Hexahydro-3-(l-methyl-5-nitro-1H-imidazol-2-yl)-l,2-benzisoxazole

“…Earlier work demonstrated that at least four dihydroxy metabolites (two fully characterized) and a t least five monohydroxy metabolites of I are found (free andlor conjugated) in dog urine (1,2). The current study shows that monohydroxylation is by far the major in uitro pathway, but that dihydroxylation is not precluded.…”

“…One of the isolated metabolites was shown to be the 7-equatorial hydroxy compound, previously identified as a canine urinary metabolite of I (2) and is thus referred to as metabolite VI (the previous designation). This is the second most abundant of the in uitro metabolites.…”

“…Although hydroxylation at C-4 of I has been recognized previously for an in uivo metabolite [4,5-di-equatorial dihydroxy, I1(2)], this is the first instance of monohydroxylation at this position.The minor metabolite fractions Y and 2 were found, on the basis ofI ' Hiiscan Bll) Svstem lIN/Hewlett-Packard 85 Toluene-ethyl acetate, 3:l; (B) methylene chloride; (C) methylene chloride-methanol, 7:l; (D) trimethylpentane-2-propanol, 4:l.…”

“…imidazol-2-yl)-1,2-benzisoxazole-synthesis of in oitro oxygenated metabolites, characterization by NMR and mass spectrometry, biotransformations on the hexahydrobenzisoxazole ring Metabolitesof 3a,4,5,6,7,7ahexahydro -3-(l-methyl-5-nitro-1H-imidazol -2-y1)-1,2-benzisoxazole, characterization by NMR and mass spectrometry Antiprotozoal agents-3a,4,5,6,7,7a-hexahydro-3-(l-methyl-5-nitro-1H-imidazol-2-yl)-l,2-benzisoxazole and its metabolites, characterization by NMR and mass spectrometry Seven canine urinary metabolites of the antiprotozoal agent 3a,4,5,6,7,7a-hexahydro-3-( l-methyl-5-nitro-lI-Iimidazol-2-yl) -1,2-benzisoxazole (MK-0436, I) have been identified; all of the compounds (11-VIII) are formed by hydroxylation of the hexahydrobenzisoxazole ring (1,2).…”

Urinary Metabolites of the Antiprotozoal Agent cis-3a,4,5,6,7,7a-Hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole in the Rat

“…Ecanow et al (7) have hypothesized that this delay in healing is partially caused by a rupturing of the cells in the wounded area from the high sugar concentrations acting as a structure breaker of these cells. The decrease in the volume of the coacervate layer in the high-concentration sugar samples may be related to the known delayed healing of wounds in diabetics with low insulin and therefore high blood sugar levels.…”