Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors.
Tumor angiogenesis is mediated by KDR and other VEGFR and PDGFR kinases. Their inhibition presents an attractive approach for developing anticancer therapeutics. Here, we report a series of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors. A number of compounds have been identified to be orally bioavailable and efficacious in the mouse edema model.
Dai
Yujia
Y
Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. yujia.dai@abbott.com
Hartandi
Kresna
K
Soni
Niru B
NB
Pease
Lori J
LJ
Reuter
David R
DR
Olson
Amanda M
AM
Osterling
Donald J
DJ
Doktor
Stella Z
SZ
Albert
Daniel H
DH
Bouska
Jennifer J
JJ
Glaser
Keith B
KB
Marcotte
Patrick A
PA
Stewart
Kent D
KD
Davidsen
Steven K
SK
Michaelides
Michael R
MR
D000284:Administration, Oral; D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014591:Uterine Diseases / Q000188:drug therapy / Q000378:metabolism
D000631:Aminopyridines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D014508:Urea; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor