Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.
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.
Chamberlain
Stanley D
SD
GlaxoSmithKline, Oncology R&D, 5 Moore Drive, 3.4184.4B, PO Box 13398, Research Triangle Park, NC 27709-3398, USA.
Wilson
Joseph W
JW
Deanda
Felix
F
Patnaik
Samarjit
S
Redman
Anikó M
AM
Yang
Bin
B
Shewchuk
Lisa
L
Sabbatini
Peter
P
Leesnitzer
M Anthony
MA
Groy
Arthur
A
Atkins
Charity
C
Gerding
Roseanne
R
Hassell
Anne M
AM
Lei
Huangshu
H
Mook
Robert A
RA
Moorthy
Ganesh
G
Rowand
Jason L
JL
Stevens
Kirk L
KL
Kumar
Rakesh
R
Shotwell
J Brad
JB
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*
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D017526:Receptor, IGF Type 1