4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: synthesis and biological evaluation.
A novel series of 4-aryl-5-cyano-2-aminopyrimidines were synthesized and found to have potent VEGF-R2 kinase inhibitory activity. Structure-activity relationships were investigated and compound 14a was shown to be efficacious in a mouse model of corneal neovascularization.
Hughes
Terry V
TV
Johnson & Johnson Pharmaceutical Research and Development, L.L.C, PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA. hughe007@hotmail.com
Emanuel
Stuart L
SL
Beck
Amanda K
AK
Wetter
Steven K
SK
Connolly
Peter J
PJ
Karnachi
Prabha
P
Reuman
Michael
M
Seraj
Jabed
J
Fuentes-Pesquera
Angel R
AR
Gruninger
Robert H
RH
Middleton
Steven A
SA
Lin
Ronghui
R
Davis
Jeremy M
JM
Moffat
David F C
DF
D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D011743:Pyrimidines; D040301:Vascular Endothelial Growth Factor Receptor-2