The thesis work is devoted to the research of quinoline-2-carboxylic acid ani-lide derivatives as potential antihypertensive drugs with diuretic effect. The most active compound 2-carboxyanilide 1-hydroxy-5-methyl-3-oxo-5,6-dihydro-3H-pyrrolo [3,2,1-ij] quinoline-2-carboxylic acid was isolated as a representative of quinoline-2-carboxylic acid anilides acid (conditional name “quinocarb”), which at a dose of 10 mg/kg showed a pronounced diuretic activ-ity (p <0.05) and the severity of the effect exceeded the hydrochlorothiazide in the equivalent dose by 1.4 (p<0.05). Upon intragastric administration to rats, the ED50 of the leader substance is 10 mg/kg, the LD50 upon intraperitoneal administration to mice and rats is 4042±735 and 3708±434 mg/kg, respective-ly, when administered intragastrically, it exceeds 5000 mg/kg (toxicity class VI). In a subchronic experiment, quinocarb with oral daily administration at a dose of 10 ED50 (100 mg/kg) to white rats during 1 month does not have a negative effect on the body weight of animals, does not change the functional state of the cardiovascular system, blood system, antitoxic and metabolic func-tions of the liver and kidneys. It has been proven that changes in the function-al activity of kidneys under the influence of the leading substance depend on the dose, duration of use and the hydration degree of the body. With long-term (7-day) administration of quinocarb in a dose of 10 mg/kg, a pronounced diu-retic effect persists for 7 days. It was found that the mechanisms of the diuretic effect of quinocarb are stipulated by a stimulating effect on the kidney dopa-mine receptors (p<0.05), an increase in glomerular filtration (p<0.05), relaxa-tion of the vascular wall, leading to an increase in the diuretic effect. Quinocarb exposes natriuretic and diuretic effects most pronounced under the terms and conditions of volumetric stimulation, which is probably the result of natriuretic hormone activation. On different models of edematous conditions (adrenaline and chloramonic pulmonary edema, osmotic cerebral edema), quinocarb at a dose of 10 mg/kg exposes pronounced decongestant properties, significantly reduces or prevents the development of pulmonary and cerebral edema, and increases the survival rate of experimental animals. According to the results of morphological studies on the model of hemodynamic pulmonary edema in rats, quinocarb at a dose of 10 mg/kg exposes a distinct anti-edematous effect at the level of the reference drug of hydrochlorothiazide at a dose of 50 mg/kg. The antihypertensive effect of quinocarb was confirmed in vivo in the model of in-domethacin arterial hypertension in rats, in SHR and in vitro on isolated rings of the aorta and renal artery of rats. Upon the terms and conditions of sponta-neous hypertension, there is a significant violation of the electrolyte composi-tion of the blood and the filtration function of the kidneys, reflected by the ac-cumulation of urea and creatinine in the SHR blood serum. Against the back-ground of the quinocarb administration at a dose of 10 mg/kg during 7 days in the SHR, blood pressure decreased (p<0.05), the electrolyte composition was restored (p<0.05), the filtration function of the kidneys improved (p<0.05), se-verity of nonspecific inflammation decreased (p<0.05). By expressiveness of the antihypertensive effect, quinocarb was not undergone to the reference drugs of enalapril (0.5 mg/kg) and hydrochlorothiazide (25 mg/kg), and by the ability to restore the filtration function of the kidneys, it exceeded their effect (p<0.05).
