SYNTHESIS AND HDAC INHIBITORY ACTIVITY OF PYRIMIDINE-BASED AMIDOXIMES, 1,2,4-OXADIAZOLES, AND 1,2,3,5-OXATHIADIAZOLES

Авторы

  • Virginija Jakubkiene Department of Organic Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, 24 Naugarduko St., 03225 Vilnius
  • Aleksandra Kopranovic Department of Chemical Engineering and Biotechnology, University of Applied Sciences, 7 Stephanstr., 64295 Darmstadt
  • Franz-Josef Meyer-Almes Department of Chemical Engineering and Biotechnology, University of Applied Sciences, 7 Stephanstr., 64295 Darmstadt
  • Sigitas Tumkevičius Department of Organic Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, 24 Naugarduko St., 03225 Vilnius

Ключевые слова:

amidoximes, nitrogen heterocycles, 1,2,4-oxadiazoles, 1,2,3,5-oxathiadiazoles, non-hydroxamate HDAC inhibitors

Аннотация

A series of new pyrimidine-based amidoximes, 1,2,4-oxadiazoles, and 1,2,3,5-oxathiadiazoles were synthesized by sequential O-alkylation of 2-substituted 6-methylpyrimidin-4(3H)-ones with chloroacetonitrile followed by the reaction of the obtained nitriles with hydroxylamine to give the corresponding amidoximes and their cyclization under the treatment with 1,1'-carbonyldiimidazole, 1,1'-thiocarbonyldiimidazole, or thionyl chloride into 1,2,4-oxadiazol-5(4H)-ones, 1,2,4-oxadiazole-5(4H)-thiones, or 3H-1,2,3,5-oxathiadiazole 2-oxides, respectively. Study of the inhibitory activity of 15 newly synthesized compounds against the human hystone deacetylase HDAC4 and HDAC8 revealed that, out of the tested series, only N'-hydroxy-2-[6-methyl-2-(piperidin-1-yl)pyrimidin-4-yloxy]acetimidamide moderately inhibited HDAC8 (IC50 5 μM).

Биографии авторов

Virginija Jakubkiene, Department of Organic Chemistry, Faculty of Chemistry and Geosciences, Vilnius University, 24 Naugarduko St., 03225 Vilnius

Faculty of Chemistry and Geosciences

assoc. prof.

Aleksandra Kopranovic, Department of Chemical Engineering and Biotechnology, University of Applied Sciences, 7 Stephanstr., 64295 Darmstadt

Department of Chemical Engineering and Biotechnology

Franz-Josef Meyer-Almes, Department of Chemical Engineering and Biotechnology, University of Applied Sciences, 7 Stephanstr., 64295 Darmstadt

Department of Chemical Engineering and Biotechnology

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Опубликован

2025-09-18

Выпуск

Том 61 № 5/6 (2025)

Раздел

Оригинальные статьи