Development of selective inhibitors against plasma kallikrein.

Specific plasma kallikrein inhibitors were disigned and synthesized and their structure-activity relationship was studied. trans-4-Aminomethylcyclohexanecarbonyl(Tra)-lysyl-4-ethoxycarbonylanilide inhibited plasma kallikrein and plasmin with IC50 values of 23 and 210 μM, respectively, indicating that this compound is fairly specific to plasma kallikrein. Tra-arginyl-4-ethoxycarbonylanilide inhibited plasma kallikrein and plasmin with IC50 values of 16 and 480 μM, respectively. Tra-homoarginyl-4-carboxyanilide inhibited plasma kallikrein and plasmin with IC50 values of 14 μM and 1 mM, respectively. Finally, Tra-Arg(Mts)-4-acetylanilide (ACA) exhibited potent and seletive inhibitory activity against plasma kallikrein (IC50 value for plasma kallikrein : 2 μM and for plasmin : 42 μM).