Pyrazolo[3,4-d]pyrimidines as potent inhibitors of the insulin-like growth factor receptor (IGF-IR).
A high throughput screen of Abbott's compound repository revealed that the pyrazolo[3,4-d]pyrimidine class of kinase inhibitors possessed moderate potency for IGF-IR, a promising target for cancer chemotherapy. The synthesis and subsequent optimization of this class of compounds led to the discovery of 14, a compound that possesses in vivo IGF-IR inhibitory activity.
Hubbard
Robert D
RD
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. robert.d.hubbard@abbott.com
Bamaung
Nwe Y
NY
Palazzo
Fabio
F
Zhang
Qian
Q
Kovar
Peter
P
Osterling
Donald J
DJ
Hu
Xiaoming
X
Wilsbacher
Julie L
JL
Johnson
Eric F
EF
Bouska
Jennifer
J
Wang
Jieyi
J
Bell
Randy L
RL
Davidsen
Steven K
SK
Sheppard
George S
GS
D000284:Administration, Oral; D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D051379:Mice; D010766:Phosphorylation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011720:Pyrazoles; D011743:Pyrimidines; D017451:Receptors, Somatomedin; C014175:pyrazolo(3,4-d)pyrimidine; D020794:Receptor Protein-Tyrosine Kinases