IN-VITRO EVALUATION AND CRYSTALLOGRAPHIC ANALYSIS OF A NEW CLASS OF SELECTIVE, NON-AMIDE-BASED THROMBIN INHIBITORS

Authors
LU TB TOMCZUK B ILLIG CR BONE R MURPHY L SPURLINO J SALEMME FR SOLL RM
Citation
Tb. Lu et al., IN-VITRO EVALUATION AND CRYSTALLOGRAPHIC ANALYSIS OF A NEW CLASS OF SELECTIVE, NON-AMIDE-BASED THROMBIN INHIBITORS, Bioorganic & medicinal chemistry letters, 8(13), 1998, pp. 1595-1600
Citations number
13
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
13
Year of publication
1998
Pages
1595 - 1600
Database
ISI
SICI code
0960-894X(1998)8:13<1595:IEACAO>2.0.ZU;2-E
Abstract
We describe the in vitro evaluation and crystallographic analysis of a new class of potent and selective, non-aminoacid-based, small-molecul e thrombin inhibitors, exemplified by 14. This class of achiral inhibi tors lacks an amide-based backbone, exhibits nM inhibition of thrombin , and is selective for thrombin. Compound 14 does not interact with th e active-site catalytic apparatus and is anchored to the enzyme via a single network of hydrogen bonds to Asp189 of the S1 pocket. (C) 1998 Elsevier Science Ltd. All rights reserved.