4-烷氧甲酰基苯并噁唑酮类化合物的合成及其体外抗炎活性研究  

Synthesis of 4-alkyloxycarbonyl-benzoxazolone compounds and their anti-inflammatory activities in vitro

作　　者：李带田 罗捷然 唐莉[1] 李青山[1,2] 

机构地区：[1]山西医科大学药学院,山西太原030001 [2]山西中医药大学,山西太原030024

出　　处：《现代药物与临床》2017年第8期1397-1402,共6页Drugs & Clinic

基　　金：国家自然科学基金资助项目(81602976);山西省青年科技研究基金(201601D021159);山西省回国留学人员重点科研资助项目(2014-重点2);山西省高等学校科技创新项目(2014132、2015150);山西医科大学博士启动金(03201319)

摘　　要：目的设计并合成4-烷氧甲酰基苯并噁唑酮类化合物,并对其进行体外抗炎活性研究。方法以3-羟基-2-氨基苯甲酸为起始原料,经过酯化、成环和取代反应合成目标化合物,并对其进行结构确证。采用LPS诱导的小鼠巨噬细胞RAW264.7炎症模型,通过Griess法测定细胞培养液中NO的释放量,ELISA法测定细胞培养液中IL-6和IL-1β的量以评价化合物的体外抗炎活性。结果共合成了10个目标化合物,均通过ESI-MS、~1H-NMR及^(13)C-NMR对其结构进行确证。体外抗炎活性测定结果表明,化合物3d在25μmol/L时对IL-1β的抑制率达63.96%,对IL-6的抑制率达60.99%,与阳性对照药塞来昔布活性相当。结论 4-烷氧甲酰基苯并噁唑酮类化合物可通过抑制NO、IL-6和IL-1β炎症因子的释放而发挥抗炎活性。Objective To design and synthesize 4-alkyloxycarbonyl-benzoxazolone compounds, and to study their anti-inflammatory activity in vitro. Methods 3-Hydroxy-2-amino benzoic acid was used as the starting material to gain a series of target compounds through esterification, cyclization, and substitution reaction, and their structures were confirmed. Subsequently, all of the synthesized compounds were incubated with lipopolysaccharide （LPS） induced rat macrophage RAW264.7 cell, then the expression of NO, IL-1β, and IL-6 were determined by Griess and ELISA assays kits to evaluate the anti-inflammatory activity in vitro. Results Ten benzoxazolone compounds were synthesized, and the structures were characterized by ESI-MS, 1H-NMR, and 13C-NMR. The anti-inflammatory activity assays showed that compound 3d had good inhibitory activity against IL-1β and IL-6 with inhibition rate of 63.96% and 60.99%, and it was near to that of the control drug celecoxib. Conclusion 4-Alkyloxycarbonyl-benzoxazolone compounds exhibit anti-inflammatory activity by inhibiting the expression of NO, IL-6 and IL-1β.

关 键 词：苯并唑酮 3-羟基-2-氨基苯甲酸 塞来昔布 合成 抗炎活性 

分 类 号：R914.2[医药卫生—药物化学] R966[医药卫生—药学]