Development of plasmin-selective inhibitors and studies of their structure-activity relationship.

Various compounds were synthesized by combining three components at positions P1, P1' and P2'. Of these, N-(trans-4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-bromobenzylo xycarbonyl)- octylamide inhibited plasmin selectively with IC50 values of 0.80 and 0.23 microM towards S-2251 and fibrin, respectively. This compound also inhibited plasma kallikrein, urokinase, thrombin and trypsin with IC50 values of 10, > 50, > 50 and 1.6 microM, respectively.