第 44 卷第 2 期Vol. 44 No. 2
2014 年 4 月Apr 2014

所属栏目:医药及中间体

囊性纤维化治疗新药Ivacaftor的合成
商青姿 (天津大学 药物科学与技术学院, 天津 300072)
摘 要:Ivacaftor是被FDA批准用于由G551D基因突变引起的囊性纤维化的治疗药物。以2,4-二叔丁基苯酚为原料,经酯化保护、硝化、水解脱保护、硝基还原得到关键中间体2,4-二叔丁基-5-氨基苯酚;苯胺和乙氧亚甲基丙二酸二乙酯经Gould-Jacobs反应得到4-氧代-1,4-二氢喹啉-3-羧酸。2,4-二叔丁基-5-氨基苯酚与4-氧代-1,4-二氢喹啉-3-羧酸缩合得到Ivacaftor,总收率约13%(以苯胺计)。
关键词:Ivacaftor;囊性纤维化;合成
中图分类号:TQ225.24  文献标识码:A  文章编号:1009-9212(2014)02-0028-06
Synthesis of Ivacaftor-A Cystic Fibrosis Drug
SHANG Qing-zi (School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China)
Abstract:Ivacaftor(1) has been approved by FDA for the treatment of cystic fibrosis caused by G551D gene mutation. It was synthesized by the reaction of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid(5)with 5-amino-2,4-di-tert-butylphenol(12) in overall yield of 13% (based on aniline). 5 was prepared via Gould-Jacobs reaction from aniline and diethyl-2-(ethoxymethylene) malonate. 12 was obtained from 2,4-di-tert-butylphenol via ester formation, nitration, ester hydrolysis and the reduction of the nitro group.
Key words:Ivacaftor; cystic fibrosis; synthesis
基金项目:天津市科委资助项目(11ZCGHHZ00800)。
作者简介:商青姿(1987-),女,山东德州人,硕士研究生,研究方向:药物化学(Email:skzqingzi@126.com)。
收稿日期: 2014-04-1