Development of Selective Inhibitors against Plasma Kallikrein

Abstract

Specific plasma kallikrein inhibitors were designed and synthesized and their structure-activity relationship was studied. tra/fs-4-Aminomethylcyclohexanecarbonyl(Tra)-lysyl-4-ethoxycarbonylanilide inhibited plasma kallikrein and plasmin with IC50 values of 23 and 210/im, 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 fiM, respectively. Tra-homoarginyl-4-carboxyanilide inhibited plasma kallikrein and plasmin with IC50 values of 14 fiM and ImM, respectively. Finally, Tra-Arg(Mts)-4-acetylanilide (ACA) exhibited potent and selective inhibitory activity against plasma kallikrein (IC50 value for plasma kallikrein: 2 pM and for plasmin: 42/im). © 1991, The Pharmaceutical Society of Japan. All rights reserved.