Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists

Authors
Barrow, JC Nantermet, PG Selnick, HG Glass, KL Ngo, PL Young, MB Pellicore, JM Breslin, MJ Hutchinson, JH Freidinger, RM Condra, C Karczewski, J Bednar, RA Gaul, SL Stern, A Gould, R Connolly, TM
Citation
Jc. Barrow et al., Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists, BIOORG MED, 11(20), 2001, pp. 2691-2696
Citations number
31
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
20
Year of publication
2001
Pages
2691 - 2696
Database
ISI
SICI code
0960-894X(20011022)11:20<2691:DAISRO>2.0.ZU;2-I
Abstract
Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, anta gonists of the thrombin receptor have potential utility for the treatment o f thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this stru cture produced 11k, which inhibits thrombin receptor stimulated secretion a nd aggregation of platelets. (C) 2001 Elsevier Science Ltd. All rights rese rved.