3-HYDROXYQUINAZOLINE-4(3H)-ONE DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS AND A METHOD FOR PRODUCTION THEREOF Russian patent published in 2021 - IPC C07D239/92 A61K31/517 

FIELD: chemistry.

SUBSTANCE: invention relates to 3-hydroxyquinazoline-4(3H)-one derivatives presented below of general formula, which can be used as histone deacetylase inhibitors. In the general formula of derivatives of 3-hydroxyquinazoline-4(3H)-one R₁ is halogen or OMe; R₂ denotes hydrogen, OMe; n = 5, 6. Invention also relates to a method of producing said compounds, which is carried out according to the following scheme. A solution of derivatives of 2-aminobenzhydroxamic acid, for example 2-amino-5-bromo-N-hydroxybenzamide or 2-amino-4,5-dimethoxy-N-hydroxybenzamide, is boiled in five-fold weight excess of formic acid for 4-6 hours. Then, the reaction mass is poured into a mixture of water with ice, alkali to pH 7 and filtered out the precipitated residue of 3-hydroxyquinazoline derivative, which is then treated with an alkylating agent, methyl 6-bromohexanoate or methyl 7-bromoheptanoate, in dimethylformamide in the presence of potassium carbonate in molar ratio of 3-hydroxyquinazoline derivative to the alkylating agent and potassium carbonate of 1:1.1:1, respectively and stirred at room temperature for 4-6 hours. After that, obtained alkylation product is precipitated by adding water, filtering, washed with water, dried, then subjected to aminolysis with 4-fold molar excess of hydroxylamine in anhydrous methanol, carried out at room temperature for 20-26 hours until formation of the end product, which is separated by filtration, followed by washing with ether.

EFFECT: there are described 3-hydroxyquinazoline-4(3H)-one derivatives as histone deacetylase inhibitors.

3 cl, 1 tbl, 12 ex