title: Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors.
abstract: The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.
authors.affiliation: Department of Medicinal Chemistry, Ambit Biosciences Corporation, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Abraham
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hadd
authors.forename: Lan
authors.initials: L
authors.lastname: Tran
authors.forename: Troy
authors.initials: T
authors.lastname: Vickers
authors.forename: Janice
authors.initials: J
authors.lastname: Sindac
authors.forename: Zdravko V
authors.initials: ZV
authors.lastname: Milanov
authors.forename: Mark W
authors.initials: MW
authors.lastname: Holladay
authors.forename: Shripad S
authors.initials: SS
authors.lastname: Bhagwat
authors.forename: Helen
authors.initials: H
authors.lastname: Hua
authors.forename: Julia M
authors.initials: JM
authors.lastname: Ford Pulido
authors.forename: Merryl D
authors.initials: MD
authors.lastname: Cramer
authors.forename: Dana
authors.initials: D
authors.lastname: Gitnick
authors.forename: Joyce
authors.initials: J
authors.lastname: James
authors.forename: Alan
authors.initials: A
authors.lastname: Dao
authors.forename: Barbara
authors.initials: B
authors.lastname: Belli
authors.forename: Robert C
authors.initials: RC
authors.lastname: Armstrong
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Treiber
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D064127:Aurora Kinases; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D014227:Triazines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases