Isolation and identification of the major urinary metabolite of 4-(4-fluorophenoxy)benzaldehyde semicarbazone after oral dosing to rats

4-(4-Fluorophenoxy)benzaldehyde semicarbazone (1) is a novel anticonvulsant affording excellent protection in the rat oral maximal electroshock (MES) screen as well as having an apparent protection index of over 300. The metabolism of this compound was studied by examining the urine or rats dosed orally with 50 mg/kg of 1 which revealed that most of the drug was converted into one metabolite 2. The structure of 2 was shown by mass spectrometry to be 1-[4-(4-fluoro-phenoxy)benzoyl]semicarbazide which was confirmed by an independent synthesis. Compound 2 was bereft of activity in the rat oral MES screen when nine times the ED50 dose of 1 was administered. This datum provided strong evidence that the anticonvulsant activity of 1 and related compounds is due to the intact molecules and is not produced by breakdown products in vivo.