Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R).
The discovery and synthesis of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one inhibitors of insulin-like growth factor 1-receptor (IGF-1R) are presented. Installing amine containing side chains at the 4-position of pyridone ring significantly improved the enzyme potency. SAR and biological activity of these compounds is presented.
Velaparthi
Upender
U
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. upender.velaparthi@bms.com
Wittman
Mark
M
Liu
Peiying
P
Stoffan
Karen
K
Zimmermann
Kurt
K
Sang
Xiaopeng
X
Carboni
Joan
J
Li
Aixin
A
Attar
Ricardo
R
Gottardis
Marco
M
Greer
Ann
A
Chang
ChiehYing Y
CY
Jacobsen
Bruce L
BL
Sack
John S
JS
Sun
Yax
Y
Langley
David R
DR
Balasubramanian
Balu
B
Vyas
Dolatrai
D
D001562:Benzimidazoles; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011728:Pyridones; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D011725:Pyridines; D011728:Pyridones; D017526:Receptor, IGF Type 1