Am. Naylorolsen et al., IDENTIFICATION AND SAR FOR A SELECTIVE, NONPEPTIDYL THROMBIN INHIBITOR, Bioorganic & medicinal chemistry letters, 8(13), 1998, pp. 1697-1702
A novel, nonpeptidyl thrombin inhibitor, L-636,619 (1), was identified
via topological similarity searching over the Merck Corporate Sample
Database. X-ray crystallographic studies determined the geometry for l
igand binding to the enzyme. Chemical modification of the P1 and P3 se
gments of the ligand resulted in enhanced potency and improvement in t
he chemical stability of the lead. Analog 9 proved to be the most inte
resting lead from this structurally novel series. (C) 1998 Elsevier Sc
ience Ltd. ATI rights reserved.