Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development.
This report describes the biological activity, characterization, and SAR leading to 9d (BMS-754807) a small molecule IGF-1R kinase inhibitor in clinical development.
Wittman
Mark D
MD
Bristol-Myers Squibb Co, Wallingford, Connecticut 06492, USA.
Carboni
Joan M
JM
Yang
Zheng
Z
Lee
Francis Y
FY
Antman
Melissa
M
Attar
Ricardo
R
Balimane
Praveen
P
Chang
Chiehying
C
Chen
Cliff
C
Discenza
Lorell
L
Frennesson
David
D
Gottardis
Marco M
MM
Greer
Ann
A
Hurlburt
Warren
W
Johnson
Walter
W
Langley
David R
DR
Li
Aixin
A
Li
Jianqing
J
Liu
Peiying
P
Mastalerz
Harold
H
Mathur
Arvind
A
Menard
Krista
K
Patel
Karishma
K
Sack
John
J
Sang
Xiaopeng
X
Saulnier
Mark
M
Smith
Daniel
D
Stefanski
Kevin
K
Trainor
George
G
Velaparthi
Upender
U
Zhang
Guifen
G
Zimmermann
Kurt
K
Vyas
Dolatrai M
DM
D000818:Animals; D035843:Biomedical Research; D004285:Dogs; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
C545990:BMS 754807; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D014227:Triazines; D017526:Receptor, IGF Type 1