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

T M Sielecki; J Liu; S A Mousa; A L Racanelli; E A Hausner; R R Wexler; R E Olson

doi:10.1016/s0960-894x(01)00406-1

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

Bioorg Med Chem Lett. 2001 Aug 20;11(16):2201-4. doi: 10.1016/s0960-894x(01)00406-1.

Authors

T M Sielecki¹, J Liu, S A Mousa, A L Racanelli, E A Hausner, R R Wexler, R E Olson

Affiliation

¹ The DuPont Pharmaceuticals Company, Experimental Station, PO Box 80500, Wilmington, DE 19880-0500, USA. [email protected]

PMID: 11514170
DOI: 10.1016/s0960-894x(01)00406-1

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.

MeSH terms

Amino Acids / chemistry
Amino Acids / pharmacology
Isoxazoles / chemical synthesis*
Isoxazoles / chemistry
Isoxazoles / pharmacology
Platelet Aggregation Inhibitors / chemistry
Platelet Aggregation Inhibitors / pharmacology
Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Amino Acids
DMP 802
Isoxazoles
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Sulfonamides
XR 299
roxifiban acetate