新型布洛芬衍生物的合成及其抗炎活性

Synthesis and Anti-inflammatory Activities of Novel Ibuprofen Derivatives

以布洛芬为原料,依次与草酰氯和氨基酸(2a^2d)反应制得中间体布洛芬衍生物(3a^3d);3与可缓慢释放H2S的5-对羟基苯基-1,2-二硫杂环戊烯-3-硫酮(4)经酯化反应,合成了4个新型的S-(+)-布洛芬衍生物(5a^5d)。α-溴乙酰氯与4经酯化反应制得5-(4-α-溴乙酰氧基)-苯基-1,2-二硫杂环戊烯-3-硫酮(6);6与1经偶联反应合成了一个新型的S-(+)-布洛芬衍生物(7),5和7的结构经1H NMR,IR和HR-MS表征。二甲苯致小鼠耳肿胀试验结果表明:5a,5c,5d和7均有较强的抗炎活性。

Four intermediates（ 3a - 3d）,ibruprofen derivatives,were prepared by reaction of ibuprofen with oxalyl chloride then amino acid（ 2a - 2d）,respectively. Four novel S-（ ＋）-ibuprofen derivatives（ 5a - 5d） were synthesized by the esterification reaction of 3 with H2 S controlled-release donor（ 5-p-hydroxyphenyl-1,2-dithicydopentene-3-thione）（ 4）. An intermediate 5-4-（ α-bromoacetoxy）-phenyl-1,2-dithio-cyclopentene-3-thione（ 6） was prepared by esferificationtion reaction of bromoacetyl chloride with 4. A novel S-（ ＋）-ibuprofen derivative（ 7） was synthesized by the coupling reaction of 6 with 1. The structures of 5 and 7 were characterized by^1 H NMR,IR and HR-MS. The results of anti-inflammation by xylene-induced mice ear swelling showed that 5a,5c,5d and 7 exhibited better anti-inflammatory activities.