METHOD OF OBTAINING HYDROXAMIC ACIDS, DERIVATIVES OF 2-ARYL-2.3-DIHYDROQUINAZOLIN-4(1H)-ONES

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, R3independently of each other are hydrogen, halogen, OMewhere R4is 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 Предлагаемое изобретение относится к способу получения гидроксамовых кислот, производных 2-арил-2,3-Дигидрохиназолин-4(1H)-ов, содержащих гидроксамовую кислоту, которые могут использоваться в медицине для лечения различных заболеваний, посредством ингибирования гистоновых деацетилаз. Предлагается способ получения гидроксамовых кислот, производных 2-арил-2,3-дигидрохиназолин-4(1H)-ов, имеющих нижеприведенную общую формулу, где R представляет собой водород или галоген; R1, R2, R3независимо друг от друга представляют собой водород, галоген, ОМе,где R4представляет собой галоген во 2-м, 3-м или 4-м положении фенильного кольца; n=4, 5. Предлагаемый способ получения соединений осуществляется с использованием в качестве исходных соединений производных гидроксамовой кислоты, а именно 2-амино-N-(6-(гидроксиамино)-6-оксогексил)бензамида, 2-амино-N-(7-(гидроксиамино)-7-оксогептил)бенза