Add time:08/08/2019         Source:sciencedirect.com

Twelve in vitro oxygenated metabolites of 3a,4,5,6,7,7a- hexahydro-3-(l-methyl-5-nitro-lH-imidazol-2-yl) -1,2-benzisoxazole (MK-0436) were produced by incubation of this antiprotozoal agent with the postmitochondriai supernatant (S9) fraction isolated from the livers of rats treated with phenobarbital. Metabolite structure elucidation was achieved using NMR and mass spectrometry. Seven monohydroxy and two dihydroxy metabolites were fully characterized; two other metabolites were partially characterized as dihydroxy derivatives of the drug. The major in vitro metabolite is the 5 axial hydroxy compound, and a minor metabolite is the corresponding ketone. In all cases metabolite formation involved biotransformation on the hexahydrobenzisoxazole ring.

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