Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase.
Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays.
Patnaik
Samarjit
S
GlaxoSmithKline, Oncology R&D, NC 27709, USA. patnaiks@mail.nih.gov
Stevens
Kirk L
KL
Gerding
Roseanne
R
Deanda
Felix
F
Shotwell
J Brad
JB
Tang
Jun
J
Hamajima
Toshihiro
T
Nakamura
Hiroko
H
Leesnitzer
M Anthony
MA
Hassell
Anne M
AM
Shewchuck
Lisa M
LM
Kumar
Rakesh
R
Lei
Huangshu
H
Chamberlain
Stanley D
SD
D015195:Drug Design; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D017526:Receptor, IGF Type 1