1. Field of the Invention
This invention relates to a series of novel oxazole derivatives which are useful as inhibitors of ADP-induced aggregation of human blood platelets in platelet-rich-plasma.
2. Description of the Art
Platelet aggregation is considered part of a complex physiological mechanism for formation of a thrombus in the vascular system. Thromboembolic phenomena, i.e., the formation of thrombi, are involved in hemostasis and a number of diseased states in mammals including thrombophlebitis, phlebothrombosis, cerebral thrombosis, coronary thrombosis and retinal vessel thrombosis. An increase in propensity for platelet aggregation, sometimes referred to as platelet adhesiveness, is observed following parturition, surgical operations such as coronary artery bypass surgery, organ transplant, angioplasty, prosthetic heart valve implants to name a few; and in ischemic heart disease, atherosclerosis, multiple sclerosis, indracranial tumors, thromboembolism, and hyperlipemia (A. Poplawski, et al, J. Atherosclerosis Research, 8: 721 (1968)).
Octimibate (1) has been revealed to be a broad spectrum inhibitor of platelet aggregation; IC.sub.50 =1 .mu.g/ml (human PRP vs ADP). (U.S. Pat. No. 4,460,598; Lautenschlager, et al Drugs of the Future, 11, 26 (1986)). ##STR2##
EPO 0434034, to Meanwell, et al. , discloses (2), which is an orally active broad spectrum inhibitor of platelet aggregation. ##STR3##
USPTO Backgrounds
USPTO Backgrounds