PYRIMIDINE DERIVATIVES HAVING MODULATION ACTIVITY ON AMPA-TYPE RECEPTORS Russian patent published in 2019 - IPC C07D239/88 A61K31/517 A61P25/26 A61P25/28 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel pyrimidine derivative of general formula (1) having properties of an AMPA-type glutamate ionotropic ammonium receptor modulator. In general formula (1)

,

R¹, R² can be identical or different substitutes, which include alkyl groups with straight or branched chain containing from 1 to 10 carbon atoms, cycloalkyl groups containing from 3 to 7 carbon atoms. Invention also relates to a method of producing compounds of formula (1). Method involves three-step synthesis involving two successive reactions of aromatic nucleophilic substitution of halogen, first into 2-alkyl- or 2-cycloalkyl-4-fluoro-5,6,7,8-tetrahydroquinazoline 1-oxide (2)

at nucleophile to form 4-[(2-alkyl/cycloalkyl-1-oxide-5,6,7,8-tetrahydroquinazolin-4-yl)oxy]phenol (3)

,

and then with compound (4) to form 4,4'-[1,4-phenylenebis(oxy)]bis(2-alkyl/cycloalkyl-5,6,7,8-tetrahydroquinazoline)-1,1'-dioxide (5), wherein the base used is sodium hydride, at the third step, reducing bis-heterocycle (5)

into pyrimidine derivative (1) under the action of phosphorus trichloride (III). To carry out the aromatic nucleophilic substitution of the halogen to the nucleophile reaction to form monosubstitution product (3), components are taken in molar ratio of 1 mole of compound (2) of at least 1 mole of hydroquinone, in order to form disubstitution product (5), components are taken in molar ratio of 1 mole of compound (3) of not less than 1 mole of compound (4)

.

Sodium hydride for aromatic nucleophilic substitution reaction is taken in ratio of not less than 1 mole per 1 mole of compound (2) or (3). For reduction of bis-heterocycle (5) into end product (1), at least 2 moles of phosphorus (III) trichloride are used per 1 mole of compound (5).

EFFECT: compounds can be used for treating neurodegenerative and psychoneurological diseases mediated by the activity of the glutamate ionotropic AMPA-type receptor.

8 cl, 2 tbl, 13 ex