PYRROLOPYRAZINE KINASE INHIBITORS Russian patent published in 2018 - IPC C07D487/04 A61K31/4985 A61P29/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I

wherein R is H; R' is C_1-6 alkoxy or or R and R' together form 4-membered heterocycloalkyl having one nitrogen atom as a ring heteroatom optionally substituted with -CN; R¹ is H or R^1a; R^1a is C_1-6alkyl, C_3-8cycloalkyl, C_1-6alkoxy, hydroxy-C_1-6alkyl or halogen-C_1-6alkyl; R¹ is H or C_1-6alkyl; or R^1a and R^1' together form 4-6-membered heterocycloalkyl containing one ring heteroatom selected from N, O and S(=O)₂, C_3-8cycloalkyl, indan-1-yl or phenyl optionally substituted with one or more R^1"; each R^1" is independently hydroxy, amino, oxo, C_1-6alkyl, -C(=O)NH₂, -CN, halogen-C_1-6alkyl, benzyl, cyano-C_1-6alkyl or -NHC(=O)OC(CH₃)₃; R² is H, hydroxy, -CN, -C(=O)OH, -C(=O)OC(CH₃)₃, R^2a or R^2b; R^2a is C_1-6alkyl, phenyl, phenyl-C_1-6alkyl, C_3-8cycloalkyl, heteroaryl, heterocycloalkyl, heterocycloalkyl-C_1-6alkyl, heteroaryl-C_1-6alkyl, phenyl-C_1-6alkoxy, C_1-6alkoxy optionally substituted by one or more R^2a', wherein heteroaryl is selected from oxazolyl, isoxazolyl, 4,5-dihydro-oxazolyl, pyridinyl, imidazolyl and pyrazolyl, and wherein heterocycloalkyl is selected from tetrahydrofuranyl, azetidinyl, oxetanyl, pyrrolidinyl and tetrahydropyranyl; each R^2a' is independently hydroxy, -CN, amino, C_1-6alkyl-sulfonylamino, C_1-6alkoxy, halogen atom, C_1-6alkyl, cyano-C_1-6alkyl, halogen-C_1-6alkyl, C_1-6alkyl-sulfonyl, halogen-C_1-6alkoxy, C_3-8cycloalkyl; R^2b is -C(=O)R³ or -CH₂C(=O)R³; R³ is heterocycloalkyl selected from piperidinyl, azetidinyl, 2-oxa-6-aza-spiro[3.3]heptyl, morpholinyl and pyrrolidinyl optionally substituted with one or more R^3'; each R^3' is independently -CN, a halogen atom or C_1-6alkyl; Q is 1H-indazol-3-yl, 4,5,6,7-tetrahydro-1H-indazol-3-yl, 1H-indol-3-yl, 5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-1-yl, imidazo[1,5-a]pyridin-1-yl, indazol-1-yl, 1H-pyrazolo[3,4-b]pyridin-3-yl, 1H-pyrazolo[4,3-b]pyridin-3-yl, imidazo[1,2-a]pyridin-3-yl, 2-hydroxy-4,5,6,7-tetrahydro-1H-indazol-3-yl, benzoimidazol-1-yl, isoquinolin-1-yl, isoquinolin-8-yl, 1H-thieno[3,2-c]pyrazol-3-yl, 1,4,5,6-tetrahydrocyclopentapriazol-3-yl, 5,6-dihydro-4H-cyclopentapyrazol-1-yl, 1,4,5,6,7,8-hexahydro-cycloheptaprazol-3-yl, 1H-indol-7-yl, 1H-pyrrolo[2,3-c]pyridin-7-yl, 1H-indazol-4-yl or 1H-indazol-7-yl optionally substituted with one or more Q^a or Q^b; each Q^a is independently a halogen atom, hydroxy or -(CH₂)_nC(=O)Q^a'; each Q^a' is independently hydroxy, amino or heterocycloalkyl, wherein heterocycloalkyl is selected from morpholinyl and piperazinyl and is optionally substituted by one or more Q^a"; each Q^a" is independently alkyl or halo-C_1-6alkyl; m is 1, 2 or 3; each Q^b is independently alkyl, C_3-8cycloalkyl, C_1-6alkoxy, phenoxy, alkyl-sulfonyl, heterocycloalkyl, heterocycloalkyl-C_1-6alkyl or heteroaryl-C_1-6alkyl optionally substituted by one or more Q^b', wherein heterocycloalkyl is selected from oxetanyl, azetidinyl, piperidinyl, pyrrolidinyl, morpholinyl and [1,3]dioxanil, and wherein heteroaryl is selected from pyridinyl, pyrazolyl, isoxazolyl and imidazolyl; and each Q^b' is independently hydroxy, a halogen atom, -CN, amino, morpholinyl, C_1-6alkyl, benzyl or C_1-6alkyl-sulfonyl; or a pharmaceutically acceptable salt thereof, inhibiting Janus kinase (JAK) and spleen tyrosine kinase (SYK) and is useful for the treatment of autoimmune and inflammatory diseases.

EFFECT: pyrrolopyrazine kinase inhibitors are proposed.

17 cl, 2 tbl, 466 ex