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Chemical stability of new acyclovir analogues with peptidomimetics
Georgi Hristov1, Ivanka Stankova
1Department of Chemistry, South-West University 'Neofit Rilski', Ivan Michailov str. 66, 2700 Blagoevgrad, Bulgaria.
Abstract:
In the search for new and effective prodrugs against the herpes simplex virus, a series of acyclovir analogues with a thiazole ring containing amino acids (glycine, alanine, valine, leucine) has been investigated. The chemical stability of some of the compounds containing different residues was studied at pH 1 and pH 7.4 at a temperature of 37°C. An HPLC method was developed for quantification of the unchanged ester concentration.Some of the esters (Gly-thiazole, Ala-thiazole-acyclovir, Leu-thiazole-acyclovir) were rather unstable, especially under acidic conditions, and underwent rapid hydrolysis into the chemical precursor acyclovir. At pH 7.4, the stability of Valthiazole-acyclovir was remarkable. At this pH, Val-thiazole-acyclovir showed stability higher than that of valacyclovir (the first effective prodrug of acyclovir).
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