title: Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38 alpha MAP kinase inhibitors.
abstract: A novel series of compounds based on the pyrrolo[2,1-f][1,2,4]triazine ring system have been identified as potent p38 alpha MAP kinase inhibitors. The synthesis, structure-activity relationships (SAR), and in vivo activity of selected analogs from this class of inhibitors are reported. Additional studies based on X-ray co-crystallography have revealed that one of the potent inhibitors from this series binds to the DFG-out conformation of the p38 alpha enzyme.
authors: Department of Immunology Chemistry, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA. stephen.wrobleski@bms.com
authors: Stephen T
authors: ST
authors: Wrobleski
authors: Shuqun
authors: S
authors: Lin
authors: John
authors: J
authors: Hynes
authors: Hong
authors: H
authors: Wu
authors: Sidney
authors: S
authors: Pitt
authors: Ding Ren
authors: DR
authors: Shen
authors: Rosemary
authors: R
authors: Zhang
authors: Kathleen M
authors: KM
authors: Gillooly
authors: David J
authors: DJ
authors: Shuster
authors: Kim W
authors: KW
authors: McIntyre
authors: Arthur M
authors: AM
authors: Doweyko
authors: Kevin F
authors: KF
authors: Kish
authors: Jeffrey A
authors: JA
authors: Tredup
authors: Gerald J
authors: GJ
authors: Duke
authors: John S
authors: JS
authors: Sack
authors: Murray
authors: M
authors: McKinnon
authors: John
authors: J
authors: Dodd
authors: Joel C
authors: JC
authors: Barrish
authors: Gary L
authors: GL
authors: Schieven
authors: Katerina
authors: K
authors: Leftheris
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D018360:Crystallography, X-Ray; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D014227:Triazines; D014409:Tumor Necrosis Factor-alpha; D048308:Mitogen-Activated Protein Kinase 14