Ring constrained analogues of beta-alanine-containing GPIIb/IIIa receptor antagonists.
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.
Sielecki
T M
TM
DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0500, USA. thais.m.sielecki@dupont.harma.com
Wityak
J
J
Liu
J
J
Mousa
S A
SA
Thoolen
M
M
Wexler
R R
RR
Olson
R E
RE
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*
D007555:Isoxazoles; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C104209:XR 299; D015091:beta-Alanine; D009584:Nitrogen