title: N-1 substituted pyrimidin-4-ones: novel, orally active inhibitors of lipoprotein-associated phospholipase A2.
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.
authors.affiliation: SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
authors.forename: H F
authors.initials: HF
authors.lastname: Boyd
authors.forename: S C
authors.initials: SC
authors.lastname: Fell
authors.forename: S T
authors.initials: ST
authors.lastname: Flynn
authors.forename: D M
authors.initials: DM
authors.lastname: Hickey
authors.forename: R J
authors.initials: RJ
authors.lastname: Ife
authors.forename: C A
authors.initials: CA
authors.lastname: Leach
authors.forename: C H
authors.initials: CH
authors.lastname: Macphee
authors.forename: K J
authors.initials: KJ
authors.lastname: Milliner
authors.forename: K E
authors.initials: KE
authors.lastname: Moores
authors.forename: I L
authors.initials: IL
authors.lastname: Pinto
authors.forename: R A
authors.initials: RA
authors.lastname: Porter
authors.forename: D A
authors.initials: DA
authors.lastname: Rawlings
authors.forename: S A
authors.initials: SA
authors.lastname: Smith
authors.forename: I G
authors.initials: IG
authors.lastname: Stansfield
authors.forename: D G
authors.initials: DG
authors.lastname: Tew
authors.forename: C J
authors.initials: CJ
authors.lastname: Theobald
authors.forename: C M
authors.initials: CM
authors.lastname: Whittaker
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism*; D015394:Molecular Structure; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D011744:Pyrimidinones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D004791:Enzyme Inhibitors; D008074:Lipoproteins; D011744:Pyrimidinones; D010741:Phospholipases A; D054467:Phospholipases A2