title: Novel and selective spiroindoline-based inhibitors of Sky kinase.
abstract: We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.
authors: Pfizer Global Research & Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. napowell@comcast.net
authors: Noel A
authors: NA
authors: Powell
authors: Jeffrey T
authors: JT
authors: Kohrt
authors: Kevin J
authors: KJ
authors: Filipski
authors: Michael
authors: M
authors: Kaufman
authors: Derek
authors: D
authors: Sheehan
authors: Jeremy E
authors: JE
authors: Edmunds
authors: Amy
authors: A
authors: Delaney
authors: Yuli
authors: Y
authors: Wang
authors: Francis
authors: F
authors: Bourbonais
authors: Doh-Yeel
authors: DY
authors: Lee
authors: Frank
authors: F
authors: Schwende
authors: Fang
authors: F
authors: Sun
authors: Pat
authors: P
authors: McConnell
authors: Cornel
authors: C
authors: Catana
authors: Huifen
authors: H
authors: Chen
authors: Jeff
authors: J
authors: Ohren
authors: Lisa A
authors: LA
authors: Perrin
mesh_terms: D000042:Absorption; D000255:Adenosine Triphosphate / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007422:Intestines / Q000187:drug effects*; D008956:Models, Chemical; D010974:Platelet Aggregation; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000255:Adenosine Triphosphate; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human