N-烷基-4-烷氧甲酰基苯并噁唑酮类化合物的合成及体外抗炎活性研究  

Synthesis and in vitro anti-inflammatory activity of N-alkyl-4-alkoxyformylbenzoxazolone derivatives

作　　者：赵蓓 李带田 罗捷然 葛睿[1] 唐莉[1] 李青山[1] ZHAO Bei;LI Dai-tian;LUO Jie-ran;GE Rui;TANG Li;LI Qing-shan(School of Pharmaceutical Science,Shanxi Medical University,Taiyuan 030001,China;Department of Pharmacy,The Central Hospital of Shaoyang,Shaoyang 422000,China)

机构地区：[1]山西医科大学药学院,山西太原030001 [2]邵阳市中心医院药学部,湖南邵阳422000

出　　处：《中国药物化学杂志》2020年第10期583-588,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(81602976);山西省青年科技研究基金项目(201901D211350);山西省回国留学人员重点科研项目(2014-重点2)

摘　　要：目的设计合成系列N-烷基-4-烷氧甲酰基苯并噁唑酮类化合物,并测定其体外抗炎活性,以期发现高活性的新化合物。方法以3-羟基-2-氨基苯甲酸为原料,经过酯化、成环和取代反应制得目标化合物,通过MS、NMR谱对其结构进行确证。建立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,采用ELISA法测定炎症因子IL-1β和IL-6的含量以评价化合物的体外抗炎活性。结果与结论合成了14个未见文献报道的新化合物,其结构均经MS、1H-NMR和13C-NMR谱确证。体外抗炎活性研究结果表明,大多数化合物对IL-1β和IL-6均呈现出较好的抑制活性,尤其是化合物3k,对IL-1β的IC50值为(1.93±0.71)μmol·L-1,明显优于阳性药塞来昔布,对IL-6的IC50值为(27.29±7.08)μmol·L-1,与阳性对照药塞来昔布活性相当,具有进一步研究的价值。Benzoxazolone has attracted the sustained attention of scientists for its diversity of biological activity.In order to find new compounds with high anti-inflammatory activity,fourteen N-alkyl-4-alkoxyformylbenzaxazolone derivatives were designed and synthesized via esterification,cyclization and substitution reaction with 3-hydroxy-2-aminobenzoic acid as the starting material.All the target compounds were characterized by MS,1H-NMR and 13C-NMR spectra.The results of anti-inflammatory activities of target compounds in LPS-induced RAW264.7 cell showed that most of the compounds presented certain inhibitory activities against NO,IL-1βand IL-6,and compound 3 k showed the highest activity against IL-1βand IL-6 with IC50 values of(1.93±0.71)μmol·L-1 and(27.29±7.08)μmol·L-1,respectively,which were higher than or equivalent to those of the positive drug celecoxib[IL-1β:IC50=(8.45±1.38)μmol·L-1,IL-6:IC50=(36.69±6.95)μmol·L-1]■.

关 键 词：N-烷基-4-烷氧甲酰基苯并噁唑酮 合成 抗炎活性 

分 类 号：R914[医药卫生—药物化学]