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

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4501-4. doi: 10.1016/j.bmcl.2003.08.070.

Abstract

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.

MeSH terms

  • 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

Substances

  • Indicators and Reagents
  • Indoles
  • Phospholipases A
  • Group IV Phospholipases A2