title: Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R).
abstract: The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.
authors.affiliation: GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. kyle.a.emmitte@Vanderbilt.edu
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Emmitte
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Wilson
authors.forename: Erich W
authors.initials: EW
authors.lastname: Baum
authors.forename: Holly K
authors.initials: HK
authors.lastname: Emerson
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Kuntz
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Nailor
authors.forename: James M
authors.initials: JM
authors.lastname: Salovich
authors.forename: Stephon C
authors.initials: SC
authors.lastname: Smith
authors.forename: Mui
authors.initials: M
authors.lastname: Cheung
authors.forename: Roseanne M
authors.initials: RM
authors.lastname: Gerding
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Stevens
authors.forename: David E
authors.initials: DE
authors.lastname: Uehling
authors.forename: Robert A
authors.initials: RA
authors.lastname: Mook
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Moorthy
authors.forename: Scott H
authors.initials: SH
authors.lastname: Dickerson
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hassell
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Leesnitzer
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: Arthur
authors.initials: A
authors.lastname: Groy
authors.forename: Jason L
authors.initials: JL
authors.lastname: Rowand
authors.forename: Kelly
authors.initials: K
authors.lastname: Anderson
authors.forename: Charity L
authors.initials: CL
authors.lastname: Atkins
authors.forename: Jingsong
authors.initials: J
authors.lastname: Yang
authors.forename: Peter
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D011725:Pyridines; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C001439:imidazo(1,2-a)pyridine; C023650:aniline