Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R).
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.
Emmitte
Kyle A
KA
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. kyle.a.emmitte@Vanderbilt.edu
Wilson
Brian J
BJ
Baum
Erich W
EW
Emerson
Holly K
HK
Kuntz
Kevin W
KW
Nailor
Kristen E
KE
Salovich
James M
JM
Smith
Stephon C
SC
Cheung
Mui
M
Gerding
Roseanne M
RM
Stevens
Kirk L
KL
Uehling
David E
DE
Mook
Robert A
RA
Moorthy
Ganesh S
GS
Dickerson
Scott H
SH
Hassell
Anne M
AM
Leesnitzer
M Anthony
MA
Shewchuk
Lisa M
LM
Groy
Arthur
A
Rowand
Jason L
JL
Anderson
Kelly
K
Atkins
Charity L
CL
Yang
Jingsong
J
Sabbatini
Peter
P
Kumar
Rakesh
R
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
D000814:Aniline Compounds; D011725:Pyridines; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C001439:imidazo(1,2-a)pyridine; C023650:aniline