Matskevych K. Experimental study of phosphorylated oxazole derivatives as potential antihypertensive agents

The thesis is dedicated to the experimental substantiation of an expediency of development of medicines with antihypertensive action on the basis of phosphorylated oxazole derivatives. In the dissertation for the first time the scientific data on vasodilatory activity of a number of original phosphorylated oxazole derivatives in vitro on isolated segments of rat aorta is established, which manifests itself as well as with simultaneous perfusion with a blocker of slow potential dependent calcium channels of L-type, verapamil. It has been proved that the leader compound 1,3-oxazole-4-yl-phosphonic acid (OVP-1) derivative belongs to the V class of "practically non-toxic compounds" at intragastric administration and to the VI class of toxicity "relatively harmless compounds" at intraperitoneal administration. With long-term use of OVP-1 for 6 months the absence of its toxic effects in rats on appearance, physiological state, behavior, body and internal organs weight, indicators of functional state of liver and heart were determined. Scientific data on the effect of oxazole derivative on cardiovascular function in anesthetized rabbits were obtained when modeling acute arterial hypertension, in particular a decrease in mean blood pressure, which may be mediated by a decrease in total peripheral vascular resistance and left ventricular working index. The effectiveness of the antihypertensive action of OVP-1 against the background of the formed stable arterial hypertension and at its formation in rats with the purpose of preventing the development of this pathology was experimentally proved. Mechanisms of antihypertensive action of oxazole derivative mediated by nitric oxide system, influence on phosphodiesterase activity, content of calcium ions and fatty acid spectrum of serum, aortic and cardiac tissues were investigated for the first time.