PYRAZOLPYRIMIDINE COMPOUNDS JAK INHIBITORS AND METHODS Russian patent published in 2015 - IPC C07D487/04 A61K31/519 A61P35/00 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula Ia, their stereoisomers or pharmaceutically acceptable salts, inhibiting JAK kinase activity. Compounds can be applied in treatment of inflammatory diseases, such as rheumatoid arthritis, psoriasis, contact dermatitis, in treatment of autoimmune diseases, such as lupus, multiple sclerosis, neurodegenerative diseases, such as Alzheimer's disease, etc. In formula Ia R¹ represents H; R² represents -OR⁴, -NR³R⁴- or -NR³S(O)₂R⁴; R³ represents H or C₁-C₆alkyl, where said alkyl is optionally substituted with OR^a; R⁴ represents H, C₁-C₆alkyl, -(C₀-C₅alkyl)(C₃-C₆cycloalkyl), -(C₀-C₅alkyl)(C₄-C₅heteroaryl), where heteroaryl contains 1-2 nitrogen atoms as heteroatoms, or -(C₀-C₅alkyl)(C₆aryl), where said alkyl is optionally substituted with group R⁸ and said aryl, cycloalkyl and heteroaryl are optionally substituted with group R⁹; or R³ and R⁴, taken together with nitrogen atom, which they are bound to, form C₃heterocyclyl, containing 1 nitrogen atom as heteroatom, optionally substituted with group R¹³; Z represents -NR⁵R⁶; R⁵ represents H; R⁶ represents H, C₁-C₁₀alkyl, -(C₀-C₅alkyl)(C₄-C₅heterocyclyl), where heterocyclyl contains oxygen atom as heteroatom, -(C₀-C₅alkyl)(C₃-C₈cycloalkyl), -(C₀-C₅alkyl)(C₃-C₅heteroaryl), where heteroaryl contains 1 nitrogen atom or 1 oxygen atom or contains 2 atoms, selected fromoxygen, nitrogen and sulphur, as heteroatoms, -(C₀-C₅alkyl)(C₆aryl), where said alkyl is optionally substituted with group R¹⁰, and said aryl, cycloalkyl, heteroaryl and heterocyclyl are optionally substituted with group R¹¹; R⁷ represents H; R⁸ and R¹⁰ each independently represents halogen or OR^a; R⁹ independently represents -CN, -CF₃, halogen, -C(O)OR^a, -C(O)NR^aR^b, -(C₀-C₅alkyl)NR^aR^b, -(C₀-C₅alkyl)OR^a, -(C₀-C₅alkyl)SR^a, -O[C(R^a)₂]_1-3O-, C₁-C₃alkyl, optionally substituted with F, -(C₀-C₅alkyl)(C₃-C₆cycloalkyl), optionally substituted with group oxo or F, -(C₀-C₅alkyl)C₃-C₆heterocyclyl, where heterocyclyl contains 1-2 heteroatoms, selected from atoms of oxygen and nitrogen, and where heterocyclyl is optionally substituted with halogen or C₁-C₃alkyl, -(C₀-C₅alkyl)C₆aryl, optionally substituted with halogen, or -(C₀-C₅alkyl)C₄-C₅heteroaryl, where heteroaryl contains 1 nitrogen atom or 1 oxygen atom or contains 2 atoms, selected from atom of oxygen, nitrogen and sulphur as heteroatoms, and where heteroaryl is optionally substituted with or C₁-C₃alkyl; R¹⁰ independently represents halogen or OR^a. Other values of radicals are given in the invention formula.

EFFECT: obtaining pharmaceutically acceptable salts, inhibiting JAK kinase activity.

15 cl, 4 tbl, 452 ex