Coronary heart disease (CHD) and hypertensive disease (HD) is the most common disorders of the cardiovascular system. Despite significant progress made in their treatment, they remain the most common causes of disability and mortality. Therapy of patients with ischemic heart disease (IHD) and arterial hypertension (AH) is an important problem of cardiology. Based on the results of the analysis of “structure-activity” among modern antianginal drugs (β-adrenoblockers, calcium blockers channels, activators of potassium channels etc.), we have theoretically proved and selected direction on creation of antianginal funds.

SPC “Pharmatron” was theoretically justified and selected direction on creation of β-adrenoceptor blocking of funds through chemical modification of molecules 1,2,4-triazole in 1 and 4 position of azaheterocycles and receive bromide 1-carboxyalkyl-4-ylideneamino-1,2,4-triazole and bromide 1-alkyl-4- ylideneamino -1,2,4-triazole. As a result of investigations, it was established that the studied compounds derived bromide 1-alkyl (carboxyalkyl)-4-ylideneamino-1,2,4-triazole belong to the III and IV toxicity class, because their LD50 intraperitoneal injection lies within 29.5–290 mg/kg.

LD50 in a series of bromide 1-alkyl (carboxyalkyl)-4-ylideneamino -1,2,4-triazole depends on the length of alkyl radical in 1 position of the molecule 1,2,4-triazole, from the nature of the substituent in para-position of benzyladenine in position 4 – introduction of methoxy groups or proton in para-position of benz- ylideneamine reduces the toxicity and introduction dimethylamino group or chlorine leads to rise. Among the 12 compounds of bromine 1-alkyl (carboxy alkyl)-4-ylideneamino-1,2,4-triazole, administered in a dose of 1/50 LD50 animals with the preliminary introduction of izadrin (adrenoagonists), 7 show the-adrenoceptor blocking activity, aimed at reducing HR.

β-adrenoceptor blocking activity in a number of bromides 1-alkyl (carboxyalkyl)-4-ylideneamino-1,2,4-triazole depends on the nature of substituent in 1 location (beta-phenylethyl, carboxypropyl, octyl) and 4 position (amino-, p-methoxybenzylylideneamino – group).

Compounds MT, AE-401, GE-81 by reducing the heart rate in animals with “load” of izadrin significantly exceed the therapeutic efficacy of metoprolol. Comparative evaluation of β-adrenoceptor blocking and physico-chemical properties of the compounds of this number identifies the most promising compounds under the working cipher MT (1-(β-phenylethyl)-4-amino-1,2,4-triazole bromide) that is neutral and stable in aqueous solutions, low toxicity (LD50 295 mg/kg), is the effect of dose 1/100 LD50. Compounds MT, the most negative chronotropic effect in the circumstances “load” of izadrin exerts significant antihypertensive effects at the doses of 1/15 1/30 and LD50, significantly reducing blood pressure in rats SHR 8% and 20% respectively. Metoprolol in the dose of 10 mg/kg had no reliable antihypertensive action of single administration to rats of line SHR. Thus, the obtained experimental data suggest that the compound MT (1-(β-phenylethyl)-4-amino-1,2,4-triazole bromide) has expressed β-adrenoceptor blocking and antihypertensive effects.

Keywords: 4-amino-1, 2, 4-triazole, β-adrenoceptor blocking action, acute toxicity

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