The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2

H F Boyd; B Hammond; D M Hickey; R J Ife; C A Leach; V A Lewis; C H Macphee; K J Milliner; I L Pinto; S A Smith; I G Stansfield; C J Theobald; C M Whittaker

doi:10.1016/s0960-894x(01)00038-5

The identification of a potent, water soluble inhibitor of lipoprotein-associated phospholipase A2

Bioorg Med Chem Lett. 2001 Mar 12;11(5):701-4. doi: 10.1016/s0960-894x(01)00038-5.

Authors

H F Boyd¹, B Hammond, D M Hickey, R J Ife, C A Leach, V A Lewis, C H Macphee, K J Milliner, I L Pinto, S A Smith, I G Stansfield, C J Theobald, C M Whittaker

Affiliation

¹ GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.

PMID: 11266173
DOI: 10.1016/s0960-894x(01)00038-5

Abstract

Modification of the pyrimidone 5-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, lipophilic inhibitors of lipoprotein-associated phospholipase A2, has given inhibitors of nanomolar potency and improved physicochemical properties. Compound 23 was identified as a potent, highly water soluble. CNS penetrant inhibitor suitable for intravenous administration.

MeSH terms

Animals
Arteriosclerosis / drug therapy
Drug Administration Routes
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology*
Humans
Male
Molecular Structure
Phospholipases A / antagonists & inhibitors*
Phospholipases A / metabolism
Phospholipases A2
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*
Rabbits
Rats
Solubility
Water / chemistry

Substances

Enzyme Inhibitors
Pyrimidinones
Water
Phospholipases A
Phospholipases A2