Flurofamide: A Potent Inhibitor of Bacterial Urease with Potential Clinical Utility in the Treatment of Infection Induced Urinary Stones

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Abstract
A novel compound, N-[diaminophosphinyl]-4-fluorobenzamide (flurofamide), has been found to be a potent inhibitor of bacterial urease. The compound, coded EU-4534, is .apprx. 1000 times more potent than acetohydroxamic acid as an inhibitor of the urease in intact Proteus mirabilis cells. Flurofamide is excreted in the urine of rats and dogs following oral administration and is effective in retarding stone formation in the urinary tract of rats infected with P. mirabilis. Measurements of urinary recoveries of urease inhibitory activity following administration of flurofamide indicate that efficacy might be achieved in humans at doses < 1 mg/kg.