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ID: ALA1153335

Journal: Bioorg Med Chem Lett

Title: Incorporation of neutral C-terminal residues in 3-amidinophenylalanine-derived matriptase inhibitors.

Authors: Schweinitz A, Dönnecke D, Ludwig A, Steinmetzer P, Schulze A, Kotthaus J, Wein S, Clement B, Steinmetzer T.

Abstract: A novel series of matriptase inhibitors based on previously identified tribasic 3-amidinophenylalanine derivatives was prepared. The C-terminal basic group was replaced by neutral residues to reduce the hydrophilicity of the inhibitors. The most potent compound 22 inhibits matriptase with a K(i) value of 0.43 nM, but lacks selectivity towards factor Xa. By combination with neutral N-terminal sulfonyl residues several potent thrombin inhibitors were identified, which had reduced matriptase affinity.

CiteXplore: 19250826

DOI: 10.1016/j.bmcl.2009.02.047