Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.
Chamberlain
Stanley D
SD
GlaxoSmithKline, Oncology R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
Redman
Anikó M
AM
Wilson
Joseph W
JW
Deanda
Felix
F
Shotwell
J Brad
JB
Gerding
Roseanne
R
Lei
Huangshu
H
Yang
Bin
B
Stevens
Kirk L
KL
Hassell
Anne M
AM
Shewchuk
Lisa M
LM
Leesnitzer
M Anthony
MA
Smith
Jeffery L
JL
Sabbatini
Peter
P
Atkins
Charity
C
Groy
Arthur
A
Rowand
Jason L
JL
Kumar
Rakesh
R
Mook
Robert A
RA
Moorthy
Ganesh
G
Patnaik
Samarjit
S
D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C538706:4,6-bis-anilino-1H-pyrrolo(2,3-d)pyrimidine; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D017526:Receptor, IGF Type 1; D048670:MAP Kinase Kinase 4