N-1 substituted pyrimidin-4-ones: novel, orally active inhibitors of lipoprotein-associated phospholipase A2

H F Boyd; S C Fell; S T Flynn; D M Hickey; R J Ife; C A Leach; C H Macphee; K J Milliner; K E Moores; I L Pinto; R A Porter; D A Rawlings; S A Smith; I G Stansfield; D G Tew; C J Theobald; C M Whittaker

doi:10.1016/s0960-894x(00)00510-2

N-1 substituted pyrimidin-4-ones: novel, orally active inhibitors of lipoprotein-associated phospholipase A2

Bioorg Med Chem Lett. 2000 Nov 20;10(22):2557-61. doi: 10.1016/s0960-894x(00)00510-2.

Authors

H F Boyd¹, S C Fell, S T Flynn, D M Hickey, R J Ife, C A Leach, C H Macphee, K J Milliner, K E Moores, I L Pinto, R A Porter, D A Rawlings, S A Smith, I G Stansfield, D G Tew, C J Theobald, C M Whittaker

Affiliation

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

PMID: 11086729
DOI: 10.1016/s0960-894x(00)00510-2

Abstract

From two related series of 2-(alkylthio)-pyrimidones, a novel series of 1-((amidolinked)-alkyl)-pyrimidones has been designed as nanomolar inhibitors of human lipoprotein-associated phospholipase A2. These compounds show greatly enhanced activity in isolated plasma. Selected derivatives such as compounds 51 and 52 are orally active with a good duration of action.

MeSH terms

Administration, Oral
Animals
Enzyme Inhibitors / administration & dosage
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Lipoproteins / metabolism*
Molecular Structure
Phospholipases A / antagonists & inhibitors*
Phospholipases A / metabolism
Phospholipases A2
Pyrimidinones / administration & dosage
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Rabbits

Substances

Enzyme Inhibitors
Lipoproteins
Pyrimidinones
Phospholipases A
Phospholipases A2