西洛司特衍生物的合成及其抗炎活性  

Synthesis and anti-inflammatory activities of cilomilast derivatives

作　　者：向伟国[1] 陈国华[1] 吴斐华[2] 李强[1] 朱航昌[1] 

机构地区：[1]中国药科大学药物化学教研室 [2]中国药科大学中药药理学教研室,南京210009

出　　处：《中国药科大学学报》2006年第4期297-300,共4页Journal of China Pharmaceutical University

摘　　要：目的：研究西洛司特衍生物的合成及其抗炎活性。方法：由4-（3-环戊氧基-4-甲氧基苯基）-4-氰基环己酮通过Darzens反应、重排和水解、酰胺化等反应合成目标化合物；应用二甲苯致小鼠耳肿胀模型评价其抗炎活性。结果：合成了11个目标化合物Ⅳ1-11，其结构经IR、ESI-MS质谱、^1H NMR和元素分析确证。结论：合成的目标化合物均未见文献报道，初步药理筛选结果显示大部分目标化合物有不同程度的抗炎活性，其中Ⅳ10的抗炎活性与西洛司特相当。Aim：To study the synthesis and anti-inflammatory activities of cyano-4- （3-cyclopentyloxy -4-methoxyphenyl ）- 1-cyclohexone as a leading cilomilast derivatives. Methods：Using 4- compound, Darzens reaction, rearrangement as well as hydrolysis and amidation were used in the synthesis of the title compounds. Their anti-inflammatory activities against mice of xylene-induced ear swelling were evaluated. Results： Eleven new compounds （ Ⅳ1- 11 ） were synthesized, and their structures were identified by IR, ^1 H NMR, ESI-MS and elemental analysis. Conclusion： The preliminary biological screenings show that most of the compounds possess inhibition activity. Among these compounds, Ⅳ10 exhibits comparable activity to that of cilomilast.

关 键 词：西洛司特 衍生物 选择性PDFA抑制剂 合成 抗炎活性 

分 类 号：TQ463.2[化学工程—制药化工]