The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70. doi: 10.1016/s0960-894x(03)00058-1.

Abstract

Modification of the pyrimidone 5-substituent in clinical candidate SB-435495 has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency. Cyclopentyl fused derivative 21, SB-480848, showed an enhanced in vitro and in vivo profile versus SB-435495 and has been selected for progression to man.

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Animals
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A / blood
  • Phospholipases A2
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology*
  • Rabbits
  • Recombinant Proteins / antagonists & inhibitors

Substances

  • Cytochrome P-450 CYP2D6 Inhibitors
  • Enzyme Inhibitors
  • Pyrimidinones
  • Recombinant Proteins
  • Phospholipases A
  • Phospholipases A2
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • darapladib