title: Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
abstract: The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.
authors.affiliation: GlaxoSmithKline, Oncology R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Chamberlain
authors.forename: Anikó M
authors.initials: AM
authors.lastname: Redman
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Wilson
authors.forename: Felix
authors.initials: F
authors.lastname: Deanda
authors.forename: J Brad
authors.initials: JB
authors.lastname: Shotwell
authors.forename: Roseanne
authors.initials: R
authors.lastname: Gerding
authors.forename: Huangshu
authors.initials: H
authors.lastname: Lei
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Stevens
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hassell
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Leesnitzer
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Smith
authors.forename: Peter
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Charity
authors.initials: C
authors.lastname: Atkins
authors.forename: Arthur
authors.initials: A
authors.lastname: Groy
authors.forename: Jason L
authors.initials: JL
authors.lastname: Rowand
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Robert A
authors.initials: RA
authors.lastname: Mook
authors.forename: Ganesh
authors.initials: G
authors.lastname: Moorthy
authors.forename: Samarjit
authors.initials: S
authors.lastname: Patnaik
mesh_terms: D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C538706:4,6-bis-anilino-1H-pyrrolo(2,3-d)pyrimidine; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D017526:Receptor, IGF Type 1; D048670:MAP Kinase Kinase 4