Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors

A series of new sulfonyl pyrrolidine derivatives was 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 compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than the positive control LY52. The FlexX docking was done to explain the reason for the different potency between MMP-2 and AP-N. Structure-activity relationships were also briefly discussed. (C) 2008 Elsevier Ltd. All rights reserved.