摘要/Abstract
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、13C 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.
关键词: PDE-4抑制剂, Crisaborole, 合成, 抗炎
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-4A (PDE-4A) 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.
Key words: PDE-4 inhibitor, crisaborole, synthesis, anti-inflammatory
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