Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists

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. (C) 2001 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.