Novel bicyclic lactam inhibitors of thrombin: Potency and selectivity optimization through P1 residues

Authors
Levesque, S St-Denis, Y Bachand, B Preveille, P Leblond, L Winocour, PD Edmunds, JJ Rubin, JR Siddiqui, MA
Citation
S. Levesque et al., Novel bicyclic lactam inhibitors of thrombin: Potency and selectivity optimization through P1 residues, BIOORG MED, 11(24), 2001, pp. 3161-3164
Citations number
8
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
24
Year of publication
2001
Pages
3161 - 3164
Database
ISI
SICI code
0960-894X(200112)11:24<3161:NBLIOT>2.0.ZU;2-L
Abstract
Peptidomimetic inhibitors of thrombin lacking the important Ser195-carbonyl interaction have been prepared. The binding energy lost after the removal of the activated carbonyl was recaptured through a series of modifications of the PI residues of the bicyclic lactam inhibitors. Selected substituted compounds displayed useful pharmacological profiles both in vitro and in vi vo. (C) 2001 Elsevier Science Ltd. All rights reserved.