α-Bromoacylureidesの生体内脱ブロム反応に関する研究(第1報) : Bromural, CarbromalおよびAcetylcarbromalの脱ブロムについて

抄録

It has been known that bromo compounds are debrominated in vivo by four types of mechanisms, i.e., reduction, hydrolysis, dehydrobromination, and mercapturic acid synthesis. Of these, reductive debromination was found recently by Curry, Tamminen, and Butler to occur in two bromoacylurea hypnotics, Bromural and Carbromal. The present investigation was undertaken in order to reconfirm whether or not this reaction is common in substances with the structure of =CBrCONHCONH-, using Bromural, Carbromal, and Acetylcarbromal. Rabbits were used as experimental animals. The detection and determination of debrominated metabolites in urine, blood, and various organs were carried out by gas and thin-layer chromatographies. The metabolites obtained from urine extracts of rabbits receiving above three drugs were purified by column chromatography, isolated as crystals, and identified as 3-methylbutyrylurea (from Bromural), and 2-ethyl-butyrylurea (from Carbromal and Acetylcarbromal), respectively. It seemed very likely that acetylcarbromal was first hydrolyzed to Carbromal and then reduced to 2-ethylbutyrylurea. It may reasonably be concluded that the bromine atom in α-position of ureid compound was displaced with hydrogen, the ureid chain remaining unchanged. It seems very interesting that this reductive debromination occurs also in a rabbit, like in man, dog, and mouse.