title: Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38α MAP kinase inhibitors.
abstract: Pyrrolo[2,1-f][1,2,4]triazine based inhibitors of p38α have been prepared exploring functional group modifications at the C6 position. Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models of acute and chronic inflammation.
authors.affiliation: Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-4000, USA. alaric.dyckman@bms.com
authors.forename: Alaric J
authors.initials: AJ
authors.lastname: Dyckman
authors.forename: Tianle
authors.initials: T
authors.lastname: Li
authors.forename: Sidney
authors.initials: S
authors.lastname: Pitt
authors.forename: Rosemary
authors.initials: R
authors.lastname: Zhang
authors.forename: Ding Ren
authors.initials: DR
authors.lastname: Shen
authors.forename: Kim W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillooly
authors.forename: David J
authors.initials: DJ
authors.lastname: Shuster
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: John S
authors.initials: JS
authors.lastname: Sack
authors.forename: Kevin
authors.initials: K
authors.lastname: Kish
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kiefer
authors.forename: John A
authors.initials: JA
authors.lastname: Newitt
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.forename: Punit H
authors.initials: PH
authors.lastname: Marathe
authors.forename: Murray
authors.initials: M
authors.lastname: McKinnon
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: John H
authors.initials: JH
authors.lastname: Dodd
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schieven
authors.forename: Katerina
authors.initials: K
authors.lastname: Leftheris
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D014227:Triazines; D048308:Mitogen-Activated Protein Kinase 14