title: Potent, orally active inhibitors of lipoprotein-associated phospholipase A(2): 1-(biphenylmethylamidoalkyl)-pyrimidones.
abstract: A series of 1-(biphenylmethylamidoalkyl)-pyrimidones has been designed as nanomolar inhibitors of recombinant lipoprotein-associated phospholipase A(2) with high potency in whole human plasma. 5-(Pyrazolylmethyl) derivative 16 and 5-(methoxypyrimidinylmethyl) derivative 27 demonstrated excellent pharmacodynamic profiles which correlated well with their pharmacokinetic effects.
authors.affiliation: GlaxoSmithKline, Medicines Research Centre, Gunnell's Wood Road, SG1 2NY, Stevenage, UK.
authors.forename: Helen F
authors.initials: HF
authors.lastname: Boyd
authors.forename: Stephen C M
authors.initials: SC
authors.lastname: Fell
authors.forename: Deirdre M B
authors.initials: DM
authors.lastname: Hickey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ife
authors.forename: Colin A
authors.initials: CA
authors.lastname: Leach
authors.forename: Colin H
authors.initials: CH
authors.lastname: Macphee
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Milliner
authors.forename: Ivan L
authors.initials: IL
authors.lastname: Pinto
authors.forename: D Anthony
authors.initials: DA
authors.lastname: Rawlings
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
authors.forename: Ian G
authors.initials: IG
authors.lastname: Stansfield
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Stanway
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Theobald
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Whittaker
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000284:Administration, Oral; D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase