萘普生2-芳基吗啉乙酯的合成及其对环氧合酶-2的抑制活性  

Synthesis and Cyclooxygenase-2 Inhibitory Activity of 2-(2-Arylmorpholino)ethyl Ester of Naproxen

作　　者：胡艾希[1] 董敏宇[1] 谢艳丽[1] 曹高[1] 叶姣[1] 

机构地区：[1]湖南大学化学化工学院,长沙410082

出　　处：《化学学报》2008年第22期2553-2557,共5页Acta Chimica Sinica

基　　金：湖南省自然基金重点(No.07JJ302)资助项目.

摘　　要：基于萘普生的构效关系对其羧基进行结构修饰,设计合成了萘普生2-芳基吗啉乙酯类化合物.芳基乙酮经过溴代、胺化、还原得到的2-芳基-4-羟乙基吗啉在三乙胺作缚酸剂存在下与萘普生酰氯反应得到萘普生2-芳基吗啉乙酯类化合物,收率24.2%～76.5%.新化合物结构经1H NMR确认.生物活性实验结果表明:在10μmol/L质量浓度时,化合物1d对COX-2的抑制率达96.32%.The 2-（2-arylmorpholino）ethyl esters of naproxen were designed and synthesized according to the structure-activity relationship by the reaction of 2-aryl-4-（2-hydroxyethyl）morpholine with 2-（6-methoxy-2-naphthyl）propionyl chloride in yields of 24.2%-76.5%. 2-Aryl-4-（2-hydroxylethyl）morpholine intermediates were synthesized from arylethanones by bromination, amination and deoxidization. Their structures were confirmed by ^1H NMR. The preliminary bioassays indicated that compound ld exhibited a 96.32% inhibition rate against COX-2 in vitro at 10μmol/L.

关 键 词：萘普生 环氧合酶-2 抑制剂 吗啉衍生物 合成 

分 类 号：TQ463.4[化学工程—制药化工]