title: Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists.
abstract: Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive mechanism for the prevention and treatment of a number of thrombotic disease states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP 754 and DMP 802 have been disclosed. In this paper, the synthesis and biological evaluation of a series of potent N-substituted benzamidine isoxazolines are explored. The effect of benzamidine substitution on the duration of antiplatelet efficacy in dog is presented.
authors.affiliation: The DuPont Pharmaceuticals Company, Experimental Station, PO Box 80500, Wilmington, DE 19880-0500, USA. thais.m.sielecki@dupontpharma.com
authors.forename: T M
authors.initials: TM
authors.lastname: Sielecki
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: S A
authors.initials: SA
authors.lastname: Mousa
authors.forename: A L
authors.initials: AL
authors.lastname: Racanelli
authors.forename: E A
authors.initials: EA
authors.lastname: Hausner
authors.forename: R R
authors.initials: RR
authors.lastname: Wexler
authors.forename: R E
authors.initials: RE
authors.lastname: Olson
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; C114713:DMP 802; D007555:Isoxazoles; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013449:Sulfonamides; C104209:XR 299; C104283:roxifiban acetate