酮洛芬合成方法研究进展  

Study of Research Progress in the Synthetic Methods of Ketoprofen

作　　者：石开云[1,2] 余清宝[2] 邹晓川[1,2] 

机构地区：[1]重庆第二师范学院药物化学研究所,重庆400067 [2]重庆第二师范学院生物与化学工程系,重庆400067

出　　处：《精细化工》2015年第8期841-848,共8页Fine Chemicals

基　　金：重庆市教委科学技术研究项目资助(KJ131513)~~

摘　　要：酮洛芬是优良的2-芳基丙酸类非甾体抗炎药物。在系统总结近年来酮洛芬生产工艺研究、改进与开发取得的新进展基础上,根据药物合成工艺设计原理,重点对具有一定工业化潜质的典型工艺路线进行了系统总结、对比分析和科学评价,包括2-(或4-)氨基二苯甲酮法、3-甲基-2-二氢吲哚酮法、2-(3-苯甲酰基苯基)丙腈法、3-氰甲基苯甲酸法合成酮洛芬和S-(+)-酮洛芬的不对称合成及其酶法拆分等。其中,2-(或4-)氨基二苯甲酮法、3-甲基-2-二氢吲哚酮法和2-(3-苯甲酰基苯基)丙腈法是实现规模化生产酮洛芬的可行方法,并指明了其工艺改进的主要研究方向,旨在为开发酮洛芬新工艺提供资鉴。Ketoprofen is a good 2-aryl propanoic acid non-steroidal anti-inflammatory drug （NSAID）. The new advances in the synthetic methods and applications of Ketoprofen in recent years have been reviewed in this paper. Based on a systematic summary of the research,improvement, and development of Ketoprofen production process, the typical process routes for the synthesis of Ketoprofen with certain industrial potentials,including 2 （or 4）-aminobenzophenone method,3-methyl-2-indolinone method,2- （3-benzoylphenyl） propanenitrile method, 3-cyanomethylbenzoic acid method, asymmetric synthesis and enzymatic resolution of S-（ ＋ ）-Ketoprofen,were analyzed and evaluated. Among these process routes,2 （ or 4 ） -aminobenzophenone method, 3 -methyl-2-indolinone method, 2 - （ 3 -benzoylphenyl ） propanenitrile method, and 3-cyanomethylbenzoic acid method may be suitable for large-scale production of Ketoprofen. The main directions for process improvement were also indicated.

关 键 词：酮洛芬 2-氨基二苯甲酮 3-甲基-2-二氢吲哚酮 2-(3-苯甲酰基苯基)丙腈 不对称合成 综论 

分 类 号：R971[医药卫生—药品] R1[医药卫生—药学]