title: 2-(Alkylthio)pyrimidin-4-ones as novel, reversible inhibitors of lipoprotein-associated phospholipase A2.
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.
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 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: M
authors.initials: M
authors.lastname: Jones
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: D A
authors.initials: DA
authors.lastname: Rawlings
authors.forename: B P
authors.initials: BP
authors.lastname: Slingsby
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
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase