METHOD OF OBTAINING HYDROXAMIC ACIDS, DERIVATIVES OF 2-ARYL-2.3-DIHYDROQUINAZOLIN-4(1H)-ONES Russian patent published in 2021 - IPC C07D239/91 A61K31/505 

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for producing hydroxamic acids, derivatives of 2-aryl-2.3-dihydroquinazolin-4(1H)-s, containing hydroxamic acid, which can be used in medicine for the treatment of various diseases by inhibiting histone deacetylases. Disclosed is a method for producing hydroxamic acids, derivatives of 2-aryl-2.3-dihydroquinazolin-4(1H)-s, having the following general formula, where R is hydrogen or halogen; R₁, R₂, R₃ independently of each other are hydrogen, halogen, OMe where R₄ is halogen at the 2nd, 3rd or 4th position of the phenyl ring; n = 4, 5. The proposed method of obtaining compounds is carried out using derivatives of hydroxamic acid as starting compounds, namely 2-amino-N-(6-(hydroxyamino) -6-oxohexyl) benzamide, 2-amino-N- (7 -(hydroxyamino) -7-oxoheptyl) benzamide or 2-amino-5-fluoro-N- (7- (hydroxyamino) -7-oxoheptyl) -benzamide, to solutions of which in tetrahydrofuran in an argon atmosphere is added a solution of substituted benzaldehyde in tetrahydrofuran in molar ratio of hydroxamic acid derivative to benzaldehyde 1: 1.1, after which the reaction mixture was stirred at room temperature for 2-3 hours, the solvent was removed in vacuum, diethyl ether was added to the residue, the crystals formed were filtered off, washed with diethyl ether and dried. The activity of a number of compounds towards the HDAC1 and HDAC6 enzymes exceeds the activity of the known histone deacetylase inhibitor Vorinostat (SAHA).

EFFECT: invention helps to obtain hydroxamic acids, derivatives of 2-aryl-2.3-dihydroquinazolin-4(1H)-s.

1 cl, 16 ex, 1 tbl