1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-associated phospholipase A(2)

J C Bloomer; H F Boyd; D M Hickey; R J Ife; C A Leach; C H Macphee; K J Milliner; I L Pinto; D A Rawlings; S A Smith; I G Stansfield; S J Stanway; M A Taylor; C J Theobald; C M Whittaker

doi:10.1016/s0960-894x(01)00346-8

1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-associated phospholipase A(2)

Bioorg Med Chem Lett. 2001 Jul 23;11(14):1925-9. doi: 10.1016/s0960-894x(01)00346-8.

Authors

J C Bloomer¹, H F Boyd, D M Hickey, R J Ife, C A Leach, C H Macphee, K J Milliner, I L Pinto, D A Rawlings, S A Smith, I G Stansfield, S J Stanway, M A Taylor, C J Theobald, C M Whittaker

Affiliation

¹ GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.

PMID: 11459662
DOI: 10.1016/s0960-894x(01)00346-8

Abstract

The lipophilic 1-substituent in a series of 1-((amidolinked)-alkyl)-pyrimidones, inhibitors of recombinant lipoprotein-associated phospholipase A(2), has been modified to give inhibitors of high potency in human plasma and enhanced physicochemical properties. Phenylpiperazineacetamide derivative 23 shows very promising oral activity.

MeSH terms

1-Alkyl-2-acetylglycerophosphocholine Esterase
Administration, Oral
Animals
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Metabolic Clearance Rate / physiology
Microsomes, Liver / metabolism
Phospholipases A / antagonists & inhibitors*
Phospholipases A / blood*
Piperazines / chemical synthesis
Piperazines / pharmacology
Pyrimidinones / chemical synthesis
Pyrimidinones / pharmacology
Rabbits
Rats

Substances

Enzyme Inhibitors
Piperazines
Pyrimidinones
Phospholipases A
1-Alkyl-2-acetylglycerophosphocholine Esterase
phenylpiperazine