title: Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase.
abstract: Novel potent trisubstituted pyridazine inhibitors of p38 MAP (mitogen activated protein) kinase are described that have activity in both cell-based assays of cytokine release and animal models of rheumatoid arthritis. They demonstrated potent inhibition of LPS-induced TNF-alpha production in mice and exhibited good efficacy in the rat collagen induced arthritis model.
authors.affiliation: Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. ntamayo@amgen.com
authors.forename: Nuria
authors.initials: N
authors.lastname: Tamayo
authors.forename: Lillian
authors.initials: L
authors.lastname: Liao
authors.forename: Martin
authors.initials: M
authors.lastname: Goldberg
authors.forename: David
authors.initials: D
authors.lastname: Powers
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tudor
authors.forename: Violeta
authors.initials: V
authors.lastname: Yu
authors.forename: Lu Min
authors.initials: LM
authors.lastname: Wong
authors.forename: Bradley
authors.initials: B
authors.lastname: Henkle
authors.forename: Scot
authors.initials: S
authors.lastname: Middleton
authors.forename: Rashid
authors.initials: R
authors.lastname: Syed
authors.forename: Timothy
authors.initials: T
authors.lastname: Harvey
authors.forename: Graham
authors.initials: G
authors.lastname: Jang
authors.forename: Randall
authors.initials: R
authors.lastname: Hungate
authors.forename: Celia
authors.initials: C
authors.lastname: Dominguez
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011724:Pyridazines; D048051:p38 Mitogen-Activated Protein Kinases