米诺膦酸关键中间体合成工艺研究进展  

Recent development of synthesis of key intermediate of minodronic acid

作　　者：欧永玉 朱冉冉 田天恩 王建耀 陈东 孙长山[2] OU Yong-yu;ZHU Ran-ran;TIAN Tian-en;WANG Jian-yao;CHEN Dong;SUN Chang-shan(Yangtze River Pharmaceutical Group,Beijing Haiyan Pharmaceutical Co.,Ltd.,Beijing 102206,China;Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]扬子江药业集团北京海燕药业有限公司,北京102206 [2]沈阳药科大学,沈阳110016

出　　处：《中国新药杂志》2021年第11期1008-1013,共6页Chinese Journal of New Drugs

摘　　要：米诺膦酸作为第三代含氮芳杂环双膦酸盐类药物,主要用于治疗骨质疏松症以及由骨质疏松症和恶性肿瘤引起的高钙血症。通过对已有文献资料的归纳总结发现,米诺膦酸的合成研究主要集中在关键中间体2-(咪唑并[1,2-a]吡啶-3-基)乙酸的合成,而该中间体的制备较大程度上是来源于咪唑并[1,2-a]吡啶母核结构的3位含有易于进行官能团转化的取代基。而由该中间体通过磷酸化合成米诺膦酸的合成技术较为单一,因此本文主要针对米诺磷酸关键中间体2-(咪唑并[1,2-a]吡啶-3-基)乙酸的合成策略进行综述。Minodronic acid is a third-generation nitrogen-containing heterocyclic bisphosphonate drug mainly used for the treatment of osteoporosis and hypercalcemia caused by osteoporosis and malignant tumors.Through summary of the existing literature,it was found that the research on the synthesis of minodronic acid is mainly concentrated on the synthesis of the key intermediate 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid,and the preparation of this intermediate is mainly based on the fact that the 3-position of the imidazo[1,2-a]pyridine’s structure contains a substituent group which is susceptible to functional group conversion.The synthesis technology of minodronic acid by phosphorylation of this intermediate is relatively simple.The synthesis strategy of the key intermediate 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid is reviewed in this article.

关 键 词：米诺膦酸 关键中间体 骨质疏松症 磷酸化 合成策略 

分 类 号：R977[医药卫生—药品]