Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity

Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-α-thrombin complex. These analogs display competitive kinetics for the inhibition of human α-thrombin. The most...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1996-06, Vol.6 (12), p.1339-1344
Main Authors: Iwanowicz, Edwin J., Lau, Wan F., Lin, James, Roberts, Daniel G.M., Seiler, Steven M.
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-α-thrombin complex. These analogs display competitive kinetics for the inhibition of human α-thrombin. The most potent member of this series 17, shows marked potency for thrombin with an inhibition constant, K i of 260 nM. Utlilizing structural information from the BMS183,507/thrombin complex together with a binding model of 5-amidinoindole led to 17 (IC 50 α-thrombin 1.4 μM; K i = 260 nM).
ISSN:0960-894X
1464-3405
DOI:10.1016/0960-894X(96)00229-6