SYNTHESIS, EVALUATION, AND CRYSTALLOGRAPHIC ANALYSIS OF L-371,912 - APOTENT AND SELECTIVE ACTIVE-SITE THROMBIN INHIBITOR

Authors
LYLE TA CHEN ZG APPLEBY SD FREIDINGER RM GARDELL SJ LEWIS SD LI Y LYLE EA LYNCH JJ MULICHAK AM NG AS NAYLOROLSEN AM SANDERS WM
Citation
Ta. Lyle et al., SYNTHESIS, EVALUATION, AND CRYSTALLOGRAPHIC ANALYSIS OF L-371,912 - APOTENT AND SELECTIVE ACTIVE-SITE THROMBIN INHIBITOR, Bioorganic & medicinal chemistry letters, 7(1), 1997, pp. 67-72
Citations number
13
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
1
Year of publication
1997
Pages
67 - 72
Database
ISI
SICI code
0960-894X(1997)7:1<67:SEACAO>2.0.ZU;2-F
Abstract
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