PDE-4抑制剂的设计、合成及生物活性研究  

Design, Synthesis, and Biological Evaluation of Novel PDE-4 Inhibitors

作　　者：高粟繁 许勤龙[2] 李家明 储昭兴[2] 何广卫[2] 林高峰 朱正伟 崔勇[2,3] 莫佳佳 郭敬[2] 赵炎[2] 

机构地区：[1]安徽中医药大学药学院,合肥230001 [2]合肥医工医药有限公司,合肥230001 [3]安徽医科大学第一附属医院,合肥230001

出　　处：《有机化学》2018年第2期478-485,共8页Chinese Journal of Organic Chemistry

基　　金：十二五国家科技重大专项(No.2012ZX09401-006)资助项目~~

摘　　要：依据药效团原理,对已报道的磷酸二酯酶(PDE-4)抑制剂Crisaborole进行结构修饰和改造,设计并合成了7个全新的小分子化合物,其结构经~1H NMR、^(13)C NMR和HRMS确证.研究其对磷酸二酯酶-4A(PDE-4A)的抑制活性、抑制炎症因子TNF-α释放效果以及抗炎活性.结果表明,所设计的7个化合物均表现出良好生物活性,其中一个化合物活性明显优于阳性对照药.Based on the reported phosphodiesterase-4（PDE-4） inhibitor of crisaborole, seven compounds with structural novelty were designed and synthesized according to the pharmacophore-combination strategy. The structures of them were identified by NMR and HRMS. Their inhibitory activities against phosphodiesterase-4 A（PDE-4 A） have been investigated. The inhibitory activities of inflammatory factor induced by lipopolysaccharide（LPS） or phorbol ester have been measured by mouse model. The results showed that all compounds exhibited high anti-inflammatory activities. In particular, one compound activity was significantly better than that of positive control drug.

关 键 词：PDE-4抑制剂 Crisaborole 合成 抗炎 

分 类 号：TQ460.1[化学工程—制药化工]