含酰基哌嗪片段的呋喃查尔酮衍生物的合成及其抗炎活性研究

摘要

A series of new 4'-(N-substitued-1-piperazinyl) furanyl chalcone derivatives have been synthesized,and their structures were characterized by1H NMR and 13C NMR.The in vitro anti-inflammatory activities of synthesized compounds were evaluated in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages.The results demonstrated that sulfamide compounds showed higher anti-inflammatory activity than their amide analogs.In particular,compound 4d was found to be the most potent anti-inflammatory compound (ICs0 =3.88μmol/L),which has a comparable activity to the positive control drug dexamethasone.%依据活性结构单元的拼合原理,以2-呋喃甲醛和4-氟苯乙酮为原料出发,经Aldol缩合、脱水、哌嗪取代反应生成4'-(1-哌嗪基)呋喃查尔酮(2)后,再与酰氯和磺酰氯反应,得到了10个未见报道的含哌嗪取代的呋喃查尔酮衍生物,其结构经1H NMR和13C NMR确证.采用小鼠巨噬细胞Raw 264.7模型初步测试了目标化合物的体外抗炎活性,结果表明,磺酰胺类化合物的抗炎活性要优于酰胺类化合物,特别是化合物4d能有效抑制NO的生成(IC50=3.88μmol/L),与阳性对照药地塞米松活性相当.