Rashed M S, Streeter A J, Nelson S D
Department of Medicinal Chemistry, University of Washington, Seattle 98195.
Drug Metab Dispos. 1989 Jul-Aug;17(4):355-9.
The hydroxamic acid of 3'-hydroxyacetanilide (AMAP) was synthesized to test the hypothesis that different reactive metabolites of AMAP and acetaminophen account for similarities in covalent binding of the two positional isomers to hepatic proteins, but for differences in their ability to cause hepatotoxicity. N-OH-AMAP was found to be a relatively stable hydroxamic acid, but it was not detected as a metabolite of AMAP formed in vitro by mouse liver microsomes or in urine of mice administered AMAP. Therefore, metabolites other than N-OH-AMAP must be responsible for covalent binding observed with AMAP to mouse liver proteins.
合成了3'-羟基乙酰苯胺的异羟肟酸（AMAP），以验证以下假设：AMAP和对乙酰氨基酚的不同反应性代谢产物导致这两种位置异构体与肝蛋白的共价结合具有相似性，但在引起肝毒性的能力上存在差异。发现N-OH-AMAP是一种相对稳定的异羟肟酸，但在小鼠肝微粒体体外形成的AMAP代谢产物或给予AMAP的小鼠尿液中未检测到它。因此，除N-OH-AMAP之外的其他代谢产物必定是AMAP与小鼠肝蛋白共价结合的原因。
