Synthesis of Tripeptide Chloromethyl Ketones and Examination of Their Inhibitory Effects on Plasmin and Plasma Kallikrein

Abstract

With the aim of obtaining selective synthetic inhibitors of plasmin and plasma kallikrein, D-Ile-Phe-Lys-CH2C1, Ile-Phe-Lys-CH2C1, D-Ile-Phe-Arg-CH2C1 and Ile-Phe-Arg-CH2C1 were synthesized and their inhibitory activity against plasmin, plasma kallikrein and other trypsin-like serine proteinases was examined. Among them, D-Ile-Phe-Arg-CH2C1 exhibited a highly selective inhibitory activity against plasma kallikrein, yet D-Ile-Phe-Lys-CH2C1 exhibited nearly the same order of inhibitory activity against plasmin as well as plasma kallikrein. © 1989, The Pharmaceutical Society of Japan. All rights reserved.