Thiophene-based vitronectin receptor antagonists.
A series of alpha(v)beta(3) antagonists based on a thiophene scaffold were synthesized via two routes and evaluated for in vitro biological activity. We have identified several structurally similar antagonists with different selectivities towards alpha(IIb)beta(3), alpha(v)beta(5) and alpha(5)beta(1) at the cellular level. In addition, these antagonists exerted an antiangiogenic effect in the chick chorioallantoic membrane (CAM) assay.
Bubenik
Monica
M
Shire BioChem Inc., 275 Armand-Frappier Blvd., Laval, Québec, Canada H7V 4A7. mbubenik@ca.shire.com
Meerovitch
Karen
K
Bergeron
Frédéric
F
Attardo
Giorgio
G
Chan
Laval
L
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects / Q000648:ultrastructure; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D020014:K562 Cells; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D006146:Guanidines; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D013876:Thiophenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C047981:arginyl-glycyl-aspartic acid