SYNTHESIS OF GLYCIVIR DERIVATIVES USING MODIFICATION OF SYNTHESIS PROCEDURE STUDYING THEIR ANTIVIRAL ACTIVITY AGAINST ENV-PSEUDOVIROUSES HIV-1
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Abstract
HIV infection still remains a global health problem around the world. The fight against infection is carried out both through preventive measures and timely testing for the presence of HIV and the use of antiretroviral therapy (ART) when it is detected. Researchers are constantly actively searching for new medicinal agents. In this work, new modified methods for the synthesis of glycivir were tested, including changing the holding time of the reaction mixture, varying the amount of starting reagents, adding catalysts, replacing the solvent, and replacing the condensing agent. Ten variants of glycivir were obtained, for each of which, using the MTT test, a 50% cytotoxic concentration was determined against the TZM-bl cell line and antiviral activity on the model of HIV-1 env-pseudoviruses. Sample 10 had the greatest activity against HIV-1 env-pseudoviruses, the synthesis of which involved the complete replacement of phosphorus and pyridine pentachloride with more accessible and less toxic methyl chloroformate and triethylamine in chloroform. These changes made to the original method for the synthesis of glycivir make it possible to obtain a drug that is most similar in biological activity to glycivir, but at the same time replace highly toxic reagents during the synthesis with less toxic and cheaper ones.
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