布洛芬衍生物的合成及抗炎镇痛活性

基于环氧合酶-2(COX-2)与COX-1结构上的差异, 设计了在布洛芬苯环3位引入取代苯甲酰胺基的系列化合物, 以期利用COX-2的侧面口袋, 增加对COX-2的结合作用. 以布洛芬为原料经五步反应合成12个目标化合物, 其结构经核磁共振氢谱、质谱和元素分析(或高分辨质谱)确证. 体外筛选结果表明, 化合物有一定的COX-2抑制活性; 对化合物7g和7h进行了体内实验, 结果表明抗炎活性弱, 但镇痛活性比较强.

Study on the Synthesis and Anti-inflammatory and Analgesic Activities of the Derivatives of Ibuprofen

Based on the structural differences between cyclooxygenase-2 (COX-2) and COX-1, a series of ibuprofen derivatives was designed, in which, a substituted benzamido group was introduced to the 3 posi- tion of the phenyl ring of ibuprofen. The purpose of this modification was to add a structural segment to oc- cupy the side pocket in COX-2 so as to enhance their affinity for COX-2. The twelve target compounds were synthesized in five steps with ibuprofen as the starting material and structurally confirmed by 1H NMR, MS and elemental analysis (or HRMS). The biological tests showed that some of them have inhibitory activity against COX-2 in vitro. Compounds 7g and 7h were evaluated in vivo and exhibited weak anti-inflammatory but potent analgesic activities.