Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity.
Novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is presented, along with successful efforts to diminish EGFR activity present in the lead series.
Munchhof
Michael J
MJ
Pfizer Global Research and Development, Groton Laboratories MS8220-2405, Eastern Point Road, Groton, CT 06340, USA. michael_j_munchhof@groton.pfizer.com
Beebe
Jean S
JS
Casavant
Jeffery M
JM
Cooper
Beth A
BA
Doty
Jonathan L
JL
Higdon
R Carla
RC
Hillerman
Stephen M
SM
Soderstrom
Catherine I
CI
Knauth
Elisabeth A
EA
Marx
Matthew A
MA
Rossi
Ann Marie K
AM
Sobolov
Susan B
SB
Sun
Jianmin
J
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D011725:Pyridines; D011743:Pyrimidines; C446540:thienopyridine; C476003:thienopyrimidine; D040301:Vascular Endothelial Growth Factor Receptor-2