title: Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR.
abstract: The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure-activity relationships of the series against p38alpha are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.
authors.affiliation: GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Angell
authors.forename: Tony D
authors.initials: TD
authors.lastname: Angell
authors.forename: Paul
authors.initials: P
authors.lastname: Bamborough
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: Murray
authors.initials: M
authors.lastname: Brown
authors.forename: Jacky B
authors.initials: JB
authors.lastname: Buckton
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Cockerill
authors.forename: Chris D
authors.initials: CD
authors.lastname: Edwards
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Jones
authors.forename: Tim
authors.initials: T
authors.lastname: Longstaff
authors.forename: Penny A
authors.initials: PA
authors.lastname: Smee
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Smith
authors.forename: Don O
authors.initials: DO
authors.lastname: Somers
authors.forename: Ann L
authors.initials: AL
authors.lastname: Walker
authors.forename: Malcolm
authors.initials: M
authors.lastname: Willson
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000577:Amides; D001713:Biphenyl Compounds; D010069:Oxadiazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases