title: Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors.
abstract: The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the regulation of cell growth and differentiation, and in protection from apoptosis. IGF-1R has been shown to be an appealing target for the treatment of human cancer. Herein, we report the synthesis, structure-activity relationships (SAR), X-ray cocrystal structure and in vivo tumor study results for a series of 2,4-bis-arylamino-1,3-pyrimidines.
authors.affiliation: Department of Medicinal Chemistry, Amgen Inc., 360 Binney Street, Cambridge, MA 02142, USA. john.buchanan@amgen.com
authors.forename: John L
authors.initials: JL
authors.lastname: Buchanan
authors.forename: John R
authors.initials: JR
authors.lastname: Newcomb
authors.forename: David P
authors.initials: DP
authors.lastname: Carney
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Chaffee
authors.forename: Lilly
authors.initials: L
authors.lastname: Chai
authors.forename: Rod
authors.initials: R
authors.lastname: Cupples
authors.forename: Linda F
authors.initials: LF
authors.lastname: Epstein
authors.forename: Paul
authors.initials: P
authors.lastname: Gallant
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Harmange
authors.forename: Kathy
authors.initials: K
authors.lastname: Hodge
authors.forename: Brett E
authors.initials: BE
authors.lastname: Houk
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Janan
authors.initials: J
authors.lastname: Jona
authors.forename: Smriti
authors.initials: S
authors.lastname: Joseph
authors.forename: H Toni
authors.initials: HT
authors.lastname: Jun
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Lu
authors.forename: Tom
authors.initials: T
authors.lastname: Menges
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morrison
authors.forename: Perry M
authors.initials: PM
authors.lastname: Novak
authors.forename: Simon
authors.initials: S
authors.lastname: van der Plas
authors.forename: Robert
authors.initials: R
authors.lastname: Radinsky
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rose
authors.forename: Satin
authors.initials: S
authors.lastname: Sawant
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Sun
authors.forename: Sekhar
authors.initials: S
authors.lastname: Surapaneni
authors.forename: Susan M
authors.initials: SM
authors.lastname: Turci
authors.forename: Keyang
authors.initials: K
authors.lastname: Xu
authors.forename: Evelyn
authors.initials: E
authors.lastname: Yanez
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; D017526:Receptor, IGF Type 1