Ogunbiyi O, Kajbaf M, Lamb J H, Jahanshahi M, Gorrod J W, Naylor S
Department of Pharmacy, King's College, University of London, UK.
Toxicol Lett. 1995 Jun;78(1):25-33. doi: 10.1016/0378-4274(94)03231-u.
We have investigated the in vitro hamster hepatic microsomal metabolism of the amino-azaheterocycle, 2-amino-1-benzylbenzimidazole (ABB). Three major metabolites were isolated and structurally characterized, using a combination of off-line HPLC, in conjunction with both electron ionization and fast atom bombardment ionization tandem mass spectrometry. ABB was shown to be debenzylated to afford 2-aminobenzimidazole (AB), as well as N- and C-oxidized to give 1-benzyl-N2-hydroxyaminobenzimidazole (BHB) and 2-amino-1-benzyl-hydroxybenzimidazole, respectively. The possible reasons for formation of the exocyclic hydroxylamine BHB are discussed. Furthermore, ABB is proposed as a suitable model compound for investigating parameters that control formation of toxic hydroxylamines derived from amino-azaheterocycles.
我们研究了氨基氮杂环化合物2-氨基-1-苄基苯并咪唑（ABB）在体外仓鼠肝微粒体中的代谢情况。使用离线高效液相色谱（HPLC）结合电子电离和快原子轰击电离串联质谱，分离并确定了三种主要代谢产物的结构。结果表明，ABB发生去苄基化反应生成2-氨基苯并咪唑（AB），同时还发生N-氧化和C-氧化反应，分别生成1-苄基-N2-羟基氨基苯并咪唑（BHB）和2-氨基-1-苄基-羟基苯并咪唑。讨论了外环羟胺BHB形成的可能原因。此外，ABB被认为是一种合适的模型化合物，可用于研究控制氨基氮杂环衍生的有毒羟胺形成的参数。
