IDENTIFICATION AND SAR FOR A SELECTIVE, NONPEPTIDYL THROMBIN INHIBITOR

Authors
NAYLOROLSEN AM PONTICELLO GS LEWIS SD MULICHAK AM CHEN ZG HABECKER CN PHILLIPS BT SANDERS WM TUCKER TJ SHAFER JA VACCA JP
Citation
Am. Naylorolsen et al., IDENTIFICATION AND SAR FOR A SELECTIVE, NONPEPTIDYL THROMBIN INHIBITOR, Bioorganic & medicinal chemistry letters, 8(13), 1998, pp. 1697-1702
Citations number
18
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
1697 - 1702
Database
ISI
SICI code
0960-894X(1998)8:13<1697:IASFAS>2.0.ZU;2-L
Abstract
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.