Patent RU-2642779-C2 (RU)
Inventor: BISSANTS KATERINA
IPC: A61K31/517
Filed: 2013-12-23
Granted: 2018-01-26
Abstract: 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 R 1  is hydrogen, methyl, Br, F or Cl; R 2  is hydrogen, lower alkyl, Br, I, C 3-6 cycloalkyl, 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 R 4 , where R 4  is F, Cl, CN, CH 2 -CN, lower alkyl, hydroxy, lower alkyl, substituted hydroxy, lower alkoxy, (CH 2 ) 1.2 -lower alkoxy, S-lower alkyl, (CH 2 ) 1.2 -S-lower alkyl, -CH 2 ) 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, (CH 2 ) 1.2 -di-lower alkylamino, (CH 2 ) 2 -NH-lower alkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, CH(CH 3 ) C(O)O-lower alkyl, O-phenyl, O-benzyl, phenyl, optionally substituted CF 3 , SF 5 , 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-(CH 2 ) 2 -morpholinyl, C(O)-NR-(CH 2 ) 2 -NR 2 , C(O)-N-di-lower alkyl, CH 2 -O-(CH 2 ) 2 -4-methylpiperazinyl, CH 2 -O-(CH 2 ) 2 -di-alkylamino, CH 2 -O-(CH 2 ) 2 -pyrrolidinyl, CH 2 -O-(CH 2 ) 2 -morpholinyl, CH 2 -O-(CH 2 ) 2 -piperidinyl optionally substituted by lower alkyl substituted by halogen or lower alkyl, (CH 2 ) 3,4 -pyrrolidinyl, (CH 2 ) 2,3 -di-lower alkylamino, morpholinyl, CH 2 -morpholinyl, CH 2 -piperazine substituted by lower alkyl, -S(O) 2 -piperazine substituted by lower alkyl, CH 2 -O-C(O)-piperazine substituted by lower alkyl, pyrazolyl or (CH 2 ) 1,2 -lower alkoxy; R is hydrogen, lower alkyl or hydroxyl; n is 0, 1, 2, or 3; or R 2  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 R 2  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 R 5 , where R 5  is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, hydroxy, (CH 2 ) 1.2 -lower alkoxy, CH 2 -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) 2 N(CH 3 ) 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; R 3  is hydrogen, methyl, Br, F, Cl, CF 3 , 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 , SO 2 CH 3 , CF 3 , 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