title: The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2.
abstract: Modification of the pyrimidone 5-substituent in clinical candidate SB-435495 has given a series of inhibitors of recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency. Cyclopentyl fused derivative 21, SB-480848, showed an enhanced in vitro and in vivo profile versus SB-435495 and has been selected for progression to man.
authors.affiliation: Medicines Research Centre, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
authors.forename: Josie A
authors.initials: JA
authors.lastname: Blackie
authors.forename: Jackie C
authors.initials: JC
authors.lastname: Bloomer
authors.forename: Murray J B
authors.initials: MJ
authors.lastname: Brown
authors.forename: Hung Yuan
authors.initials: HY
authors.lastname: Cheng
authors.forename: Beverley
authors.initials: B
authors.lastname: Hammond
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: V Ann
authors.initials: VA
authors.lastname: Lewis
authors.forename: Colin H
authors.initials: CH
authors.lastname: Macphee
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Milliner
authors.forename: Kitty E
authors.initials: KE
authors.lastname: Moores
authors.forename: Ivan L
authors.initials: IL
authors.lastname: Pinto
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: Maxine A
authors.initials: MA
authors.lastname: Taylor
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Theobald
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000097:blood; D054467:Phospholipases A2; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D001713:Biphenyl Compounds; D004048:Diethylamines; D013440:Sulfides
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; D011744:Pyrimidinones; D011994:Recombinant Proteins; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D013440:Sulfides