Novel 2-oxoamide inhibitors of human group IVA phospholipase A(2)

J Med Chem. 2002 Jul 4;45(14):2891-3. doi: 10.1021/jm025538p.

Abstract

A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA(2) activity at 0.009 mole fraction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Group IV Phospholipases A2
  • Humans
  • Magnetic Resonance Spectroscopy
  • Norleucine / analogs & derivatives*
  • Norleucine / chemical synthesis*
  • Norleucine / chemistry
  • Phospholipases A / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amides
  • Enzyme Inhibitors
  • Norleucine
  • Phospholipases A
  • Group IV Phospholipases A2
  • PLA2G4A protein, human