Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity

Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-α-thrombin complex. These analogs display competitive kinetics for the inhibition of human α-thrombin. The most potent member of this series 17, shows marked potency for thrombin with an inhibition constant, Ki of 260 nM.