酮洛芬合成方法研究进展

Study Advances on the Synthetic Methods of Ketoprofen

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。

Abstract:

Ketoprofen is a good 2-aryl propanoic acid non-steroidal anti-inflammatory drug (NSAID). The new advances on its synthetic methods and applications of Ketoprofen in recent years have been reviewed in this paper. Based on systematically summarizing the research, improvement, and development of Ketoprofen production process, the typical process routes for 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 to processes improvement were also indicated.