SUMMARY
The article describes the study of the antihypoxic action of the compounds previously synthesized, namely indole and 2-oxindole derivatives, containing an ethylamine fragment being characteristic of melatonin, and the “chemical structure – antihypoxic action” dependence based on in vivo and in silico data. The screening has been conducted on the models of acute normobaric and hemic hypoxia in white male mice. The substances under research were administered in the dose of 0.50 mg/kg that was similar to the reference drug melatonin.The second antihypoxic reference drug mexidol was administered in the dose of 42 mg / kg. The compound R-77 (4,3’-spiro[(2-amino-3-cyano-4,5-dihydro-pyrano[3,2-c]chromen-5-on)-5-methyl-2’-oxindole]) caused a maximum effect (of about 101% on the hemic hypoxia model, and 176% on the normobaric hypoxia model). By its effect size the new compound is significantly superior to the reference drug melatonin (the antihypoxic activity is 67.6% and 109%) and somewhat dominates mexidol (the antihypoxic activity is 94.3 % and 161%). A set of essential molecular descriptors (miLogP, TPSA, MV) has been calculated for each of the 30 compounds. The compounds having lipophilicity (miLogP) estimated approximately from 1.2 to 2.5, the calculated topological descriptor of the polar surface molecules area (TPSA) from 85 to 125 and the optimal molecular volume (MV) 250 to 320 have shown the highest antihypoxic activity. The results obtained demonstrate the expediency of a further detailed pharmacological study of spirocyclic oxindole derivatives for the purpose of searching for highly efficient substances with the antihypoxic action.