title: 1-(Arylpiperazinylamidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-associated phospholipase A(2).
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.
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, Essex, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Bloomer
authors.forename: H F
authors.initials: HF
authors.lastname: Boyd
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: I L
authors.initials: IL
authors.lastname: Pinto
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: S J
authors.initials: SJ
authors.lastname: Stanway
authors.forename: M A
authors.initials: MA
authors.lastname: Taylor
authors.forename: C J
authors.initials: CJ
authors.lastname: Theobald
authors.forename: C M
authors.initials: CM
authors.lastname: Whittaker
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate / Q000502:physiology; D008862:Microsomes, Liver / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000097:blood*; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D011744:Pyrimidinones; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C031503:phenylpiperazine