Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase.
Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.
Cee
Victor J
VJ
Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA. vcee@amgen.com
Cheng
Alan C
AC
Romero
Karina
K
Bellon
Steve
S
Mohr
Christopher
C
Whittington
Douglas A
DA
Bak
Annette
A
Bready
James
J
Caenepeel
Sean
S
Coxon
Angela
A
Deak
Holly L
HL
Fretland
Jenne
J
Gu
Yan
Y
Hodous
Brian L
BL
Huang
Xin
X
Kim
Joseph L
JL
Lin
Jasmine
J
Long
Alexander M
AM
Nguyen
Hanh
H
Olivieri
Philip R
PR
Patel
Vinod F
VF
Wang
Ling
L
Zhou
Yihong
Y
Hughes
Paul
P
Geuns-Meyer
Stephanie
S
D000284:Administration, Oral; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors*
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D042787:Receptor, TIE-2