title: Ring constrained analogues of beta-alanine-containing GPIIb/IIIa receptor antagonists.
abstract: A series of ring constrained analogues of the GPIIb/IIIa receptor antagonist XR299 (1) was investigated as potential inhibitors of glycoprotein IIb/IIIa, a platelet receptor that plays a key role in platelet aggregation and platelet adhesion. Ring size was found to have a large effect on in vitro potency. Selected compounds showed good in vitro activity, a preference for binding to activated platelets, and modest duration of action when dosed i.v. as a racemate in a canine model.
authors.affiliation: DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0500, USA. thais.m.sielecki@dupont.harma.com
authors.forename: T M
authors.initials: TM
authors.lastname: Sielecki
authors.forename: J
authors.initials: J
authors.lastname: Wityak
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: S A
authors.initials: SA
authors.lastname: Mousa
authors.forename: M
authors.initials: M
authors.lastname: Thoolen
authors.forename: R R
authors.initials: RR
authors.lastname: Wexler
authors.forename: R E
authors.initials: RE
authors.lastname: Olson
mesh_terms: D006801:Humans; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D007555:Isoxazoles; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C104209:XR 299; D015091:beta-Alanine; D009584:Nitrogen