Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (PMS1062) derivatives specific for group II enzyme

Bioorg Med Chem. 2005 Mar 15;13(6):1989-2007. doi: 10.1016/j.bmc.2005.01.016.

Abstract

We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A(2) (hGIIA PLA(2)) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA(2) versus porcine group IB PLA(2). The SAR results, as well as the logP and pK(a) values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Inhibitory Concentration 50
  • Molecular Structure
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry*
  • Oxazoles / pharmacology*
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A / classification
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Structure-Activity Relationship

Substances

  • 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one
  • Enzyme Inhibitors
  • Oxazoles
  • Phospholipases A
  • Phospholipases A2