3H－1，2－二氢－2－（4－甲基苯胺基）甲基－1－吡咯里嗪酮在家兔体内主要代谢产物的研究  

STUDY ON MAJOR METABOLITES OF 3H-1,2-DIHYDRO-2-(4-METHYLPHENYLAMINO)-METHYL-1-PYRROLIZINONE IN RABBITS

作　　者：钟大放[1] 顾景凯[1] 陈仁弟[1] 罗旭[1] 

机构地区：[1]沈阳药科大学药学系

出　　处：《药学学报》1996年第11期855-860,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：用高效液相色谱法对家兔单剂量ｉｇ７５０ｍｇ新抗炎镇痛剂３Ｈ－１，２二氢－２－（４－甲基苯胺基）－甲基－１－吡咯里嗪酮（Ｚ－４７）后尿中的代谢物进行了分离、检测。根据代谢物的色谱行为及与Ｚ－４７结构有关的其它药物的代谢途径，推测Ｚ－４７羧基衍生物［４－（３Ｈ－１，２－二氢－１－吡咯里嗪酮－２－甲基胺基）苯甲酸］是一可能的代谢产物，遂用化学方法合成了该衍生物。利用色谱保留值、紫外双波长吸收比值等对代谢物和标准品进行比较，并对尿样的酶水解产物进行色谱分析，证实Ｚ－４７羧基衍生物及其酯型β－Ｄ－葡糖苷酸结合物是Ｚ－４７在家兔体内的主要代谢产物。The metabolites of a 750 mg oral dose of Z-47 [3H-1,2-dihydro-2(4-methylphenylamino)methyl-1-pyrrolizinone],a new anti-inflammatory and analgesic agent,in rabbiturine were separated and detected with high performance liquid chromatographic methed.On basis ofthe chromatographic behavior of Z-47 metabolites and biotransformation pathways of drugs with partialstructure of Z-47,the carboxylic derivative of Z-47 [4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid] was proposed as a potential metabolite so that the compound wassynthesized.The authentic substance was then compared with one of the metahalites by thechromatographic retention time and the ratio of their UV-absorbances at two wavelengths.Theenzyme-hydrolyzed product of another metabolite was also analysed.It was consequently confirmedthat the carboxylic derivative of Z-47 and its acyl β-D-glucuronide are major metabolits of Z-47 inrabbits.

关 键 词：吡咯里嗪酮 合成 甲基苯胺基 消炎镇痛药 

分 类 号：TQ463.53[化学工程—制药化工] R971.1[医药卫生—药品]