NEW ETERIAL DERIVATIVES OF ISOXAZOLE AS POSITIVE ALLOSTERIC MODULATORS OF THE GABA A ALFA 5 RECEPTOR Russian patent published in 2022 - IPC C07D413/14 A61K31/4439 A61K31/501 A61P25/28 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where X is selected from N and CH; Y is selected from N and CR¹⁰; Z is selected from N and CR¹¹; R¹ is selected from i) C_1-6-alkyl, ii) halo- C_1-6-alkyl, iii) C_1-6-alkoxy, iv) halo- C_1-6-alkoxy, v) hydroxy-C1-6-alkyl, vi ) C_3-8-cycloalkyl, vii) halogen and viii) amino substituted on the nitrogen atom with one or two substituents independently selected from H, C1-6-alkyl and C_3-8-cycloalkyl; R² is selected from H and halo; R³ is selected from i) H, ii) C_1-6 alkyl, iii) C_3-8 cycloalkyl, iv) hydroxy C_1-6 alkyl, and v) halo C_1-6 alkyl; R⁴ is selected from i) H, ii C_1-6 alkyl, iii) C_1-6 alkoxy, iv) C_3-8 cycloalkyl, and v) halogen; R⁵ is H; R⁶ is selected from i) H, ii) C_1-6 alkyl, iii) C_3-8 cycloalkyl substituted with R⁷, R⁸ and R⁹, iv) C_3-8-cycloalkyl-C1-6-alkyl substituted with R⁷, R⁸ and R⁹, v) C_1-6-alkylsulfonyl- C_1-6-alkyl, vi) cyano- C_1-6-alkyl, vii) hydroxy- C_1-6-alkyl, viii) dihydroxy- C_1-6-alkyl, ix) halo- C_1-6-alkyl, x) heterocycloalkyl substituted with R⁷, R⁸ and R⁹, where heterocycloalkyl is selected from oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, thiolanyl, oxaspiro- [3.3]-heptanyl, tetrahydrothiopyranyl, 7-oxabicyclo[2.2.1]heptanyl and oxepanyl, and xi) heterocycloalkyl- C_1-6-alkyl substituted with R⁷, R⁸ and R⁹, where heterocycloalkyl is oxetanyl; R¹⁰ is selected from i) H, ii) C_1-6 alkyl, iii) C_1-6 alkoxy, iv) C_3-8 cycloalkyl, and v) halogen; ^R11 is selected from i) H, ii) C_1-6 alkyl, iii) C_1-6 alkoxy, iv) C_3-8 cycloalkyl, and v) halogen; or R⁵ and R¹⁰ together form -( CH₂)_n-; or R⁵ and R11 together form -(CH₂)_n-; or R⁵ and R⁶ together with the nitrogen atom to which they are attached form a heterocycloalkyl substituted with R⁷, R⁸ and R⁹, where the heterocycloalkyl is azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, oxa-6-azaspiro[3.3]heptanyl, 2-thia-6-azaspiro[3.3]heptanyl,3-oxa-6-azabicyclo[3.1.1]heptanyl,thiomorpholinyl or azaspiro[3.3]heptanyl; n is selected from 1 and 2; or pharmaceutically acceptable salts. The invention also relates to the use of compounds of formula (I) for the use or prevention of diseases associated with GABA α5 receptors.

EFFECT: compounds that are selective positive allosteric modulators (PAM) of GABAA α5 receptors.

15 cl, 2 tbl, 193 ex