Cheng Xian-Chao, Wang Qiang, Fang Hao, Tang Wei, Xu Wen-Fang
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
Eur J Med Chem. 2008 Oct;43(10):2130-9. doi: 10.1016/j.ejmech.2007.12.020. Epub 2007 Dec 31.
A series of novel pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The hydroxamates 8a-c were equally or more potent MMP-2 inhibitors than the positive control LY52. The binding mode of the most potent compound 8a with MMP-2 was proposed. Structure-activity relationships were also briefly discussed.
设计、合成了一系列新型吡咯烷衍生物，并测定了它们对基质金属蛋白酶2（MMP-2）和氨肽酶N（AP-N）的抑制活性。结果表明，与AP-N相比，这些吡咯烷衍生物对MMP-2表现出高度选择性抑制。异羟肟酸酯8a-c作为MMP-2抑制剂的活性与阳性对照LY52相当或更强。提出了最有效的化合物8a与MMP-2的结合模式。还简要讨论了构效关系。
