title: The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38alpha MAP kinase inhibitor.
abstract: A novel structural class of p38alpha MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38alpha inhibitor that is orally efficacious in rodent models of acute and chronic inflammation.
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA. john.hynes@bms.com
authors.forename: John
authors.initials: J
authors.lastname: Hynes
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Sidney
authors.initials: S
authors.lastname: Pitt
authors.forename: Ding Ren
authors.initials: DR
authors.lastname: Shen
authors.forename: Rosemary
authors.initials: R
authors.lastname: Zhang
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schieven
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillooly
authors.forename: David J
authors.initials: DJ
authors.lastname: Shuster
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Taylor
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Yang
authors.forename: Kim W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: Murray
authors.initials: M
authors.lastname: McKinnon
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.forename: Punit H
authors.initials: PH
authors.lastname: Marathe
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Kevin
authors.initials: K
authors.lastname: Kish
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kiefer
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.forename: John A
authors.initials: JA
authors.lastname: Newitt
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: John
authors.initials: J
authors.lastname: Dodd
authors.forename: Katerina
authors.initials: K
authors.lastname: Leftheris
mesh_terms: D000818:Animals; D001168:Arthritis / Q000188:drug therapy; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C529303:BMS-640994; D065607:Cytochrome P-450 Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System; D048308:Mitogen-Activated Protein Kinase 14