2-(Alkylthio)pyrimidin-4-ones as novel, reversible inhibitors of lipoprotein-associated phospholipase A2

H F Boyd; S T Flynn; D M Hickey; R J Ife; M Jones; C A Leach; C H Macphee; K J Milliner; D A Rawlings; B P Slingsby; S A Smith; I G Stansfield; D G Tew; C J Theobald

doi:10.1016/s0960-894x(00)00002-0

2-(Alkylthio)pyrimidin-4-ones as novel, reversible inhibitors of lipoprotein-associated phospholipase A2

Bioorg Med Chem Lett. 2000 Feb 21;10(4):395-8. doi: 10.1016/s0960-894x(00)00002-0.

Authors

H F Boyd¹, S T Flynn, D M Hickey, R J Ife, M Jones, C A Leach, C H Macphee, K J Milliner, D A Rawlings, B P Slingsby, S A Smith, I G Stansfield, D G Tew, C J Theobald

Affiliation

¹ SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.

PMID: 10714508
DOI: 10.1016/s0960-894x(00)00002-0

Abstract

Starting from two weakly active hits from high throughput screening, a novel series of 2-(alkylthio)-pyrimidin-4-ones with high potency and selectivity for lipoprotein-associated phospholipase A2 has been designed. In contrast to previously known inhibitors, these have been shown to act by a non-covalent and substrate competitive mechanism.

MeSH terms

1-Alkyl-2-acetylglycerophosphocholine Esterase
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Phospholipases A / antagonists & inhibitors*
Phospholipases A2
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*
Structure-Activity Relationship
Substrate Specificity

Substances

Enzyme Inhibitors
Pyrimidinones
Phospholipases A
Phospholipases A2
1-Alkyl-2-acetylglycerophosphocholine Esterase