title: Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity.
abstract: The biphenyl amides (BPAs) are a novel series of p38alpha MAP kinase inhibitor. The optimisation of the series to give compounds that are potent in an in vivo disease model is discussed. SAR is presented and rationalised with reference to the crystallographic binding mode.
authors.affiliation: GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Angell
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Aston
authors.forename: Paul
authors.initials: P
authors.lastname: Bamborough
authors.forename: Jacky B
authors.initials: JB
authors.lastname: Buckton
authors.forename: Stuart
authors.initials: S
authors.lastname: Cockerill
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: deBoeck
authors.forename: Chris D
authors.initials: CD
authors.lastname: Edwards
authors.forename: Duncan S
authors.initials: DS
authors.lastname: Holmes
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Jones
authors.forename: Dramane I
authors.initials: DI
authors.lastname: Laine
authors.forename: Shila
authors.initials: S
authors.lastname: Patel
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
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: D001549:Benzamides; D001713:Biphenyl Compounds; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14