IDO INHIBITORS Russian patent published in 2017 - IPC C07D487/04 A61K31/4188 A61P37/02 

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, in particular, to derivatives of imidazo[5,1-a]isoindole of structure given below, or to a stereoisomer or pharmaceutically acceptable salt thereof, where bond α is a single or double bond; n = 0 or 1; R¹: halogen or -OR; R²: -C_1-4alkyl-R^A or -C_2-4alkenyl-R³, if bond α is a single bond; and R²: =C(H)R^A, if bond α is a double bond; in which R^A: -CN, -C(O)R³, -C(O)OR³, -C(O)N(R³)(R^C), -C(OR^B)(R³)(R^C), -C(NHR^B)(R³)(R^C), or -C(=N-OR^C)R³, where R^B: hydrogen, -C(O)R³, -C(O)N(H)R³, -C(O)(CH₂)₂COOR, -C(O)(CH₂)_1-4(NR)COOR, -C(O)CH(NH₂)(R^D), or -P(O)(OR³)₂; where R^D: methyl or -CH(CH₃)₂; R³: hydrogen, C_1-6alkyl, phenyl, imidazolyl, furanyl, thiazolyl, pyridinyl, C_5-6cycloalkyl, C_3-8cycloalkenyl, piperidinyl, pyrrolidinyl, tetrahydropyranyl, azetidinyl or C₆cycloalkylC₁alkyl-, where each alkyl, cycloalkyl, piperidinyl, pyrrolidinyl, tetrahydropyranyl and azetidinyl is optionally and independently substituted with one group =R³² and optionally and independently substituted with one or two groups R³¹; each phenyl, imidazolyl, furanyl, thiazolyl and pyridinyl is optionally substituted with one or two groups R³¹; where R³¹: halogen, nitro, C_1-6alkyl, -C_1-6alkyl-R³³, C_1-6haloalkyl, -OR, -N(R)₂, -C(O)OR, -C(O)N(R)₂, -C(O)R, -S(O)₂R, -OC(O)R, -N(R)C(O)R or -N(R)C(O)OR, where R³³: -OR; R³²: =O, =C(R³⁴)₂, =(spiro-C_3-8cycloalkyl), or =(spirodioxalanyl), where R³⁴: hydrogen, halogen, C_1-6alkyl or -C₁alkyl-OR; R^C: hydrogen or C_1-6alkyl; and R: hydrogen or R¹⁰, where R¹⁰: C_1-6alkyl, phenyl, thiophenyl, C_5-6cycloalkyl, pyrrolidinyl, tetrahydropyranyl, phenylC_1-6alkyl, heteroarylC_1-2alkyl- (where heteroaryl group is a pyridine, pyrimidine or imidazole) or tetrahydropyranC₁alkyl, where each of alkyl, phenyl, cycloalkyl and phenylC_1-2alkyl optionally substituted with one or two groups, which independently represent a halogen, C_1-6alkyl, C₁haloalkyl, -OR¹¹, -N(R¹¹)₂ or -N(R¹¹)S(O)₂R¹¹, where R¹¹: hydrogen or C_1-6alkyl. Invention also relates to specific compounds, pharmaceutical composition based on declared imidazo[5,1-a]isoindole and a method of treating indoleamine-2,3-dioxygenase (IDO) mediated immunosuppression.

EFFECT: novel derivatives of imidazo[5,1-a]isoindole are obtained, having useful biological properties.

42 cl, 1 dwg, 75 ex