title: Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.
abstract: The evaluation of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines as inhibitors of the IGF-1R (IGF-IR) receptor tyrosine kinase is reported. Examples demonstrate nanomolar potencies in in vitro enzyme and mechanistic cellular assays as well as promising in vivo pharmacokinetics in rat.
authors.affiliation: GlaxoSmithKline, Oncology R&D, 5 Moore Drive, 3.4184.4B, PO Box 13398, Research Triangle Park, NC 27709-3398, USA.
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Chamberlain
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Wilson
authors.forename: Felix
authors.initials: F
authors.lastname: Deanda
authors.forename: Samarjit
authors.initials: S
authors.lastname: Patnaik
authors.forename: Anikó M
authors.initials: AM
authors.lastname: Redman
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Lisa
authors.initials: L
authors.lastname: Shewchuk
authors.forename: Peter
authors.initials: P
authors.lastname: Sabbatini
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Leesnitzer
authors.forename: Arthur
authors.initials: A
authors.lastname: Groy
authors.forename: Charity
authors.initials: C
authors.lastname: Atkins
authors.forename: Roseanne
authors.initials: R
authors.lastname: Gerding
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hassell
authors.forename: Huangshu
authors.initials: H
authors.lastname: Lei
authors.forename: Robert A
authors.initials: RA
authors.lastname: Mook
authors.forename: Ganesh
authors.initials: G
authors.lastname: Moorthy
authors.forename: Jason L
authors.initials: JL
authors.lastname: Rowand
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Stevens
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: J Brad
authors.initials: JB
authors.lastname: Shotwell
mesh_terms: D000818:Animals; D055808:Drug Discovery; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D017526:Receptor, IGF Type 1