Synthetic inhibitors of serine proteinases. 34. The effect of modification of the amidino function of N-alpha-substituted 4-amidinophenylalanine amides on inhibitory activity

Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are selective inhibitors of thrombin. The exchange of the amidino function for an aminomethyl residue does not influence the selectivity and potency of their inhibitory activity. In contrast, the modification of the amidino function of the N alpha-arylsulfonylaminoacylated compound N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide results in a drastic loss of inhibitory activity. Only the oxamidino derivative possesses considerable high affinity for thrombin. Obviously, in tight binding inhibitors of thrombin structural variation results in any case in a loss of inhibitory activity.