COMT INHIBITORS Russian patent published in 2018 - IPC C07D239/88 C07D401/04 C07D401/10 C07D401/12 C07D403/04 C07D403/10 C07D405/04 C07D409/04 C07D409/14 C07D413/14 C07D417/04 C07D417/10 C07D471/04 A61K31/517 A61P25/00 

FIELD: pharmacology.

SUBSTANCE: invention relates to new compounds of the formula (I) and their pharmaceutically acceptable salts which have the properties of a catechol-O-methyltransferase (COMT) inhibitor. In the compound of the formula (I)

,

where R¹ is hydrogen, methyl, Br, F or Cl; R² is hydrogen, lower alkyl, Br, I, C_3-6cycloalkyl, C(O)O-lower alkyl, C(O)NH-lower alkyl substituted by halogen, C(O)(morpholine) or is 3,4-dihydronaphthalen-2-yl optionally substituted by lower alkyl, 1,2,3,4-tetrahydronaphthalen-2-yl, 2,3-dihydrobenzofuran-6-yl, 1-methyl-2,3-dihydro-1H-indolin-5-yl, 1-methylindolin-5-yl, tetrahydropyran-4-yl, 3,6-dihydro-2H-pyran-4-yl, 2-isopropyl-1,2,3-tetrahydroisoquinolin-5-yl, 2,3-dihydro- dimethyl[1,4]dioxin-6-yl, benzo[1,3]-dioxol-5-yl, 1,2,3,4-tetrahydroisoquinolin-7-yl optionally substituted by lower alkyl, cyclohexenyl, morpholinyl, 4-methylpiperazinyl, naphthalen-1-yl, naphtalen-2-yl, or represents (CHR)_n-phenyl optionally substituted by one to five substituents R⁴, where R⁴ is F, Cl, CN, CH₂-CN, lower alkyl, hydroxy, lower alkyl, substituted hydroxy, lower alkoxy, (CH₂)_1.2-lower alkoxy, S-lower alkyl, (CH₂)_1.2-S-lower alkyl, -CH₂)_1.2-S (O)₂-lower alkyl, -S(O)₂-lower alkyl, -S(O)₂-di-lower alkylamino, -S(O)₂-piperidinyl, lower alkyl substituted by halogen, -N=N-phenyl, di-lower alkylamino, (CH₂)_1.2-di-lower alkylamino, (CH₂)₂-NH-lower alkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, CH(CH₃) C(O)O-lower alkyl, O-phenyl, O-benzyl, phenyl, optionally substituted CF₃, SF₅, benzyl, C(O)-lower alkyl, C(O)-phenyl, C(O)-morpholinyl, C(O)-4-methylpiperazinyl, C(O)-di-oxothiomorpholinyl, C(O)-piperidinyl, optionally substituted by F, C(O)-NH-(CH₂)₂-morpholinyl, C(O)-NR-(CH₂)₂-NR₂, C(O)-N-di-lower alkyl, CH₂-O-(CH₂)₂-4-methylpiperazinyl, CH₂-O-(CH₂)₂-di-alkylamino, CH₂-O-(CH₂)₂-pyrrolidinyl, CH₂-O-(CH₂)₂-morpholinyl, CH₂-O-(CH₂)₂-piperidinyl optionally substituted by lower alkyl substituted by halogen or lower alkyl, (CH₂)_3,4-pyrrolidinyl, (CH₂)_2,3-di-lower alkylamino, morpholinyl, CH₂-morpholinyl, CH₂-piperazine substituted by lower alkyl, -S(O)₂-piperazine substituted by lower alkyl, CH₂-O-C(O)-piperazine substituted by lower alkyl, pyrazolyl or (CH₂)_1,2-lower alkoxy; R is hydrogen, lower alkyl or hydroxyl; n is 0, 1, 2, or 3; or R² is C(O)-phenyl optionally substituted by lower alkyl; or is -O-phenyl optionally substituted by F; or is CH=CH-phenyl optionally substituted by lower alkyl; or is C≡C-phenyl; or R² is a heteroaryl selected from the group consisting of pyrazolyl, thiazolyl, pyridinyl, pyrimidinyl, imidazolyl, isoxazolyl, isothiazolyl, thiophenyl, 1-thia-3,4-diazolyl, imidazo[1,2-a]pyridinyl, indazolyl, quinolinyl or isoquinolinyl, and the said groups are optionally substituted by R⁵, where R⁵ is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, hydroxy, (CH₂)_1.2-lower alkoxy, CH₂-di-lower alkylamino, di-lower alkylamino, morpholinyl, piperazinyl, pyrrolidin-1-yl, C(O)-piperidinyl, C(O)-4-methylpiperazinyl, phenyl optionally substituted by halogen, pyridinyl, S(O)₂N(CH₃)₂, C(O)O-lower alkyl, NHC(O)-lower alkyl, or is C(O)-heteroaryl selected from pyridinyl and thiophenyl, where heteroaryl groups are optionally substituted by lower alkyl, n is 0, 1, 2 or 3; R³ is hydrogen, methyl, Br, F, Cl, CF₃, nitro, amino, cyano, NHC(O)-phenyl, or is 1-methyl-1,2,3,6-tetrahydropyridinyl, or is pyridinyl optionally substituted by methyl or morpholinyl, or is phenyl optionally substituted by methyl , SO₂CH₃, CF₃, CN, F or C(O)N (di-lower alkyl).

EFFECT: compounds can be used to treat Parkinson's disease, depression, cognitive impairment and motor symptoms, resistant depression, cognitive impairment, mood and negative symptoms of schizophrenia.

16 cl, 2 tbl, 256 ex