Synthesis and structure-activity relationship study of the new set of trypsin-like proteinase inhibitors

A new set of 25 trypsin-like proteinase inhibitors was prepared and the inh ibiting activity on trypsin, thrombin, plasmin and urokinase was measured. The structure-activity relationship is discussed. High inhibiting activitie s were observed in 4-guanidinobenzoic acid esters only. The replacement of this moiety for N-formamidinyl-isonipecotic acid or an arginine moiety caus ed almost total loss of the activity. In the series of 4-guanidinobenzoic a cid eaters, any important influence of the eater-groups reactivity was obse rved. The trypsin-thrombin selectivity in the compounds with the guanidine- remote carboxylic function was also observed. (C) 1999 Editions scientifiqu es et medicales Elsevier SAS.