Thienopyridine urea inhibitors of KDR kinase.
A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.
Heyman
H Robin
HR
Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. robin.heyman@abbott.com
Frey
Robin R
RR
Bousquet
Peter F
PF
Cunha
George A
GA
Moskey
Maria D
MD
Ahmed
Asma A
AA
Soni
Niru B
NB
Marcotte
Patrick A
PA
Pease
Lori J
LJ
Glaser
Keith B
KB
Yates
Melinda
M
Bouska
Jennifer J
JJ
Albert
Daniel H
DH
Black-Schaefer
Candace L
CL
Dandliker
Peter J
PJ
Stewart
Kent D
KD
Rafferty
Paul
P
Davidsen
Steven K
SK
Michaelides
Michael R
MR
Curtin
Michael L
ML
D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D004958:Estradiol; D005260:Female; D051379:Mice; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014591:Uterine Diseases / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D011725:Pyridines; C446540:thienopyridine; D004958:Estradiol; D014508:Urea; D040301:Vascular Endothelial Growth Factor Receptor-2