Structure-activity relationships of indole cytosolic phospholipase A(2)alpha inhibitors: substrate mimetics

An SAR effort focused on generating cPLA(2)alpha inhibitors using a substrate mimetic approach is reported. Indole inhibitors of cPLA(2)alpha with promising pharmacokinetic parameters that were active in both an isolated enzyme assay and in cell-based assays were discovered. Modeling these compounds...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2003-12, Vol.13 (24), p.4501-4504
Main Authors: McKew, John C, Lovering, Frank, Clark, James D, Bemis, Jean, Xiang, YiBin, Shen, Marina, Zhang, Wen, Alvarez, Juan C, Joseph-McCarthy, Diane
Format: Article
Language:English
Subjects:
Binding Sites
Group IV Phospholipases A2
Indicators and Reagents
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Kinetics
Molecular Conformation
Phospholipases A - antagonists & inhibitors
Phospholipases A - chemistry
Protein Conformation
Static Electricity
Structure-Activity Relationship
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:An SAR effort focused on generating cPLA(2)alpha inhibitors using a substrate mimetic approach is reported. Indole inhibitors of cPLA(2)alpha with promising pharmacokinetic parameters that were active in both an isolated enzyme assay and in cell-based assays were discovered. Modeling these compounds into the cPLA(2)alpha structure validated the assumptions made at the start of the SAR effort.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2003.08.070