Optimisation of the P2 pharmacophore in a series of thrombin inhibitors: Ion-dipole interactions with lysine 60G

Authors
Ambler, J Brown, L Cockcroft, XL Grutter, M Hayler, J Janus, D Jones, D Kane, P Menear, K Priestle, J Smith, G Talbot, M Walker, CV Wathey, B
Citation
J. Ambler et al., Optimisation of the P2 pharmacophore in a series of thrombin inhibitors: Ion-dipole interactions with lysine 60G, BIOORG MED, 9(9), 1999, pp. 1317-1322
Citations number
6
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
9
Year of publication
1999
Pages
1317 - 1322
Database
ISI
SICI code
0960-894X(19990503)9:9<1317:OOTPPI>2.0.ZU;2-V
Abstract
The optimisation of the P2 pharmacophore in a series of thrombin inhibitors is described. The interaction of a number of piperidine P2 functionalities with lysine 60G of thrombin is explored with reference to the crystal stru cture of inhibitor enzyme complexes. A primary ion-dipole interaction betwe en the terminal P2 side chain group and lysine 60G is evoked to explain the SAR in this series. (C) 1999 Elsevier Science Ltd. All rights reserved.