Urinary Metabolites of 3a,4,5,6,7,7a‐Hexahydro‐3‐(1‐methyl‐5‐nitro‐1H‐imidazol‐2‐yl)‐1,2‐benzisoxazole in the Dog

The antiprotozoal drug 3a,4,5,6,7,7a‐hexahydro‐3‐(1‐methyl‐5‐nitro‐1H‐imidazol‐2‐yl)‐1,2‐benzisoxazole (I), which exhibits activity against trypanosomiasis, is also antibacterialin vivo. Since the urine from a dog dosed with I showed a broader spectrum of antibacterial activity than I itself, metabolites from this urine were isolated and partially characterized. The metabolites were mono‐ and dihydroxy‐substituted species with the hydroxyl groups on carbons 4‐7 of the hexahy‐drobenzisoxazole ring. These observations led to the synthesis of several such hydroxy derivatives of I, and their properties fully supported the proposed positions of metabolic hydroxylation. One synthetic compound, the 6,7‐cis‐dihydroxy compound, exhibited higher antibacterial activity againstSalmonella schottmuelleriin mice and greater trypanocidal activityin vivoagainstTrypanosoma cruzi(Brazil strain) than I.