The ester of thioctic (α-lipoic) acid and 2-ethyl-6-methyl-3-hydroxypyridine was synthesized. The toxicity decreased while the antihypoxic activity simultaneously increased for an equimolar mixture of thioctic acid and 2-ethyl-6-methyl-3-hydroxypyridine after they were combined into 2-ethyl-6-methylpyridinol-3-yl thioctate (laboratory name thioxypine). The tolerance to asphyxia increased by 51%; to hypercapnic hypoxia, by 47% after intraperitoneal (i.p.) administration of thioxypine at a dose of 145 μmol/kg. Such a combination of effects corresponded to the formal criteria for classifying thioxypine as an antihypoxant. A fourfold reduction in the dosage of thioxypine (to 36.25 μmol/kg) reduced the resistance to histotoxic hypoxia by 32%. The synthesized ether did not affect the resistance to hemic hypoxia.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 57, No. 3, pp. 14 – 19, March, 2023.
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Volchegorskii, I.A., Grobovoi, S.I., Sinitskii, A.I. et al. Synthesis, Toxicological Evaluation, and Antihypoxic Effect of 2-Ethyl-6-Methylpyridinol-3-yl Thioctate. Pharm Chem J 57, 347–352 (2023). https://doi.org/10.1007/s11094-023-02888-z
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DOI: https://doi.org/10.1007/s11094-023-02888-z