Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity.
Compound 3 (BMS-536924), a novel small-molecule inhibitor of the insulin-like growth factor receptor kinase with equal potency against the insulin receptor is described. The in vitro and in vivo biological activity of this interesting compound is also reported.
Wittman
Mark
M
Discovery Chemistry, Department of Metabolism and Pharmacokinetics, Department of Computer Aided Drug Design, and Department of Chemical Synthesis, Bristol-Myers Squibb Co, 5 Research Parkway, Wallingford, Connecticut 06492, USA. mark.wittman@bms.com
Carboni
Joan
J
Attar
Ricardo
R
Balasubramanian
Balu
B
Balimane
Praveen
P
Brassil
Patrick
P
Beaulieu
Francis
F
Chang
Chiehying
C
Clarke
Wendy
W
Dell
Janet
J
Eummer
Jeffrey
J
Frennesson
David
D
Gottardis
Marco
M
Greer
Ann
A
Hansel
Steven
S
Hurlburt
Warren
W
Jacobson
Bruce
B
Krishnananthan
Subramaniam
S
Lee
Francis Y
FY
Li
Aixin
A
Lin
Tai-An
TA
Liu
Peiying
P
Ouellet
Carl
C
Sang
Xiaopeng
X
Saulnier
Mark G
MG
Stoffan
Karen
K
Sun
Yax
Y
Velaparthi
Upender
U
Wong
Henry
H
Yang
Zheng
Z
Zimmermann
Kurt
K
Zoeckler
Mary
M
Vyas
Dolatrai
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D000882:Haplorhini; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000187:drug effects; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; C504983:BMS 536924; D001562:Benzimidazoles; D011725:Pyridines; D011728:Pyridones; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin