Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors

• DOI: 10.1016/j.ejmech.2007.12.020
• Publication Date: 2008-01-02T22:35:04Z
• Authors: Xian-Chao Cheng; Qiang Wang; Hao Fang; Wei Tang; Wen-Fang Xu
• Keywords: Models, Molecular; Pyrrolidines; Molecular Conformation; CD13 Antigens; Matrix Metalloproteinase Inhibitors; 01 natural sciences; Matrix Metalloproteinases; 0104 chemical sciences; Drug Design; Matrix Metalloproteinase 2; Amino Acid Sequence; Enzyme Inhibitors

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.