Removal of the beta-ketoamide functionality from L370,518 (K-i = 0.09
nM) provided a 5 nM K-i inhibitor of thrombin: L-371,912. Comparison o
f the enzyme-inhibitor crystal structures suggests a possible explanat
ion for the relatively small change in affinity for thrombin. L-371,91
2 is selective for thrombin over related serine proteases and is effic
acious in an animal model of arterial thrombosis. Copyright (C) 1996 E
lsevier Science Ltd