Hydrolytic cleavage of the pyrimidine ring in 2-aryl-[1,2,4]triazole[1,5-c]quinazolines: physico-chemical properties and the hypoglycemic activity of the compounds synthesized

S. V. Kholodnyak, K. P. Schabelnyk, G. A. Shernova, T. Yu. Sergeieva, V. V. Ivchuk, O. Yu. Voskoboynik, S. I. Kovalenko, S. D. Trzhetsinskiy, S. I. Okovytyy, S. V. Shishkina

Abstract


It has been shown that 2-aryl-[1,2,4]triazolo[1,5-c]-quinazolines under the action of nucleophilic agents (hydrazine hydrate, sodium hydroxide, sodium methoxide, hydrochloric acid) undergo hydrolytic cleavage followed by formation of [2-(3-aryl-1H-1,2,4-triazol-5-yl)-phenyl]amines. The rational synthetic protocols for the compounds mentioned above, namely heating in the hydrochloric acid solution at 90-95°C for 60 min, have been proposed. It has been found that substituents in position 2 of the triazoloquinazoline moiety do not significantly affect duration of the reaction and the yields of products. Purity and the structure of the compounds synthesized have been proven by the corresponding physicochemical methods, namely: elemental analysis, LC-MS, 1H, 13C NMR-spectrometry and X-ray structural study. The azole-azole prototropic tautomery has been substantiated using physicochemical analytical methods. According to the data obtained in gas or DMSO medium compounds 2 exist as tautomer A or C, while in the crystal lattice the anilines mentioned exist as A-form. It has been determined that 2-(3-aryl-1H-1,2,4-triazol-5-yl)phenyl]amines (2.1, 2.8, 2.14) in the dose of 10 mg/kg are as good as reference-drugs Metformin (in the doses of 50 and 200 mg/kg) and Gliclazide (in the dose of 50 mg/kg) by their hypoglycemic activity when assessing specific pharmacological activities in oral glucose tolerance test (OGTT), rapid insulin and adrenaline test models.


Keywords


2-aryl-[1,2,4]triazolo[1,5-c]quinazolines; hydrolytic cleavage; hypoglycemic activity

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DOI: https://doi.org/10.24959/88922

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