Design, Synthesis and pharmacological evaluation of new compounds 1,2,5-oxadiazole-2-oxide useful as preventive of atherothrombosis.

Abstract

In Brazil, cardiovascular diseases account for the increased mortality rate in all regions, representing 30% of all deaths in the country in individuals between 30 and 69 years. Among cardiovascular diseases, atherosclerosis is highly prevalent. The disease is progressive and characterized by the accumulation of lipids and fibrous components in arteries leading to the formation of atheromas. These decrease or block the caliber of the vessels causing ischemic events. There is a close association between atherosclerosis and atherothrombosis. After the rupture or erosion of atherosclerotic plaque is extravasated prothrombotic contents into the circulation leading to platelet adhesion and aggregation, thrombin generation, fibrin and thrombus formation. Due to the essential activity of platelets in thromboembolic disease, antiplatelet drugs have important therapeutic value as a preventive atherothrombosis in reducing morbidity and mortality due to atherothrombotic disease. The AAS is one of the most used antiplatelet drugs in the prevention of atherothrombosis. The drug inhibits the formation of thromboxane (platelet aggregation inducer and vasoconstrictor properties holder). However, AAS use has limitations as a series of induction of gastric ulcers, weak inhibition of platelet function, blocking only one pathway mediated by thromboxane interpaciente variable and response ("resistance") with weak inhibition of aggregation in some patients. Once therapy with aspirin has limitations and undesirable effects, the use of tools such as molecular changes, such as the hybridization is a strategy for discovery of more effective antiplatelet drugs. In this context, through the agency of different pathways: inhibition of thromboxane associated with the donation of nitric oxide by spaced subunit N-acyl hydrazone, is being sought synthetically compounds with antiplatelet activity are optimized for the original prototype AAS.