Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites / drug effects
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CD13 Antigens / antagonists & inhibitors*
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Computer Simulation
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Dose-Response Relationship, Drug
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Drug Design*
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Matrix Metalloproteinase Inhibitors*
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Models, Chemical
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Molecular Conformation
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Sulfones / chemical synthesis
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Sulfones / chemistry
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Sulfones / pharmacology*
Substances
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Matrix Metalloproteinase Inhibitors
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Protease Inhibitors
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Pyrrolidines
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Sulfones
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CD13 Antigens