title: Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment.
abstract: Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.
authors.affiliation: Wyeth Research, Chemical & Screening Sciences, Princeton, NJ, USA. millerl9@wyeth.com
authors.forename: Lori M
authors.initials: LM
authors.lastname: Miller
authors.forename: Scott C
authors.initials: SC
authors.lastname: Mayer
authors.forename: Dan M
authors.initials: DM
authors.lastname: Berger
authors.forename: Diane H
authors.initials: DH
authors.lastname: Boschelli
authors.forename: Frank
authors.initials: F
authors.lastname: Boschelli
authors.forename: Li
authors.initials: L
authors.lastname: Di
authors.forename: Xuemei
authors.initials: X
authors.lastname: Du
authors.forename: Minu
authors.initials: M
authors.lastname: Dutia
authors.forename: Middleton B
authors.initials: MB
authors.lastname: Floyd
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.forename: Cynthia Hess
authors.initials: CH
authors.lastname: Kenny
authors.forename: Girija
authors.initials: G
authors.lastname: Krishnamurthy
authors.forename: Franklin
authors.initials: F
authors.lastname: Moy
authors.forename: Susan
authors.initials: S
authors.lastname: Petusky
authors.forename: Diane
authors.initials: D
authors.lastname: Tkach
authors.forename: Nancy
authors.initials: N
authors.lastname: Torres
authors.forename: Biqi
authors.initials: B
authors.lastname: Wu
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D006801:Humans; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D011804:Quinolines; D017526:Receptor, IGF Type 1