title: Thiophene-based vitronectin receptor antagonists.
abstract: 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.
authors.affiliation: Shire BioChem Inc., 275 Armand-Frappier Blvd., Laval, Québec, Canada H7V 4A7. mbubenik@ca.shire.com
authors.forename: Monica
authors.initials: M
authors.lastname: Bubenik
authors.forename: Karen
authors.initials: K
authors.lastname: Meerovitch
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bergeron
authors.forename: Giorgio
authors.initials: G
authors.lastname: Attardo
authors.forename: Laval
authors.initials: L
authors.lastname: Chan
mesh_terms: 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
chemical_list: 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