PYRAZOLPYRIMIDINE COMPOUNDS JAK INHIBITORS AND METHODS

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 IaRrepresents H; Rrepresents -OR, -NRR- or -NRS(O)R; Rrepresents H or C-Calkyl, where said alkyl is optionally substituted with OR; Rrepresents H, C-Calkyl, -(C-Calkyl)(C-Ccycloalkyl), -(C-Calkyl)(C-Cheteroaryl), where heteroaryl contains 1-2 nitrogen atoms as heteroatoms, or -(C-Calkyl)(Caryl), where said alkyl is optionally substituted with group Rand said aryl, cycloalkyl and heteroaryl are optionally substituted with group R; or Rand R, taken together with nitrogen atom, which they are bound to, form Cheterocyclyl, containing 1 nitrogen atom as heteroatom, optionally substituted with group R; Z represents -NRR; Rrepresents H; Rrepresents H, C-Calkyl, -(C-Calkyl)(C-Cheterocyclyl), where heterocyclyl contains oxygen atom as heteroatom, -(C-Calkyl)(C-Ccycloalkyl), -(C-Calkyl)(C-Cheteroaryl), where heteroaryl contains 1 nitrogen atom or 1 oxygen atom or contains 2 atoms, selected fromoxygen, nitrogen and sulphur, as heteroatoms, -(C-Calkyl)(Caryl), where said alkyl is optionally substituted with group R, and said aryl, cycloalkyl, heteroaryl and heterocyclyl are optionally substituted with group R; Rrepresents H; Rand Reach independently represents halogen or OR; Rindependently represents -CN, -CF, halogen, -C(O)OR, -C(O)NRR, -(C-Calkyl)NRR, -(C-Calkyl)OR, -(C-Calkyl)SR, -O[C(R)]O-, C-Calkyl, optionally substituted with F, -(C-Calkyl)(C-Ccycloalkyl), optionally substituted with group oxo or F, -(C-Calkyl)C-Cheterocyclyl, where heterocyclyl contains 1-2 heteroatoms, selected from atoms of oxygen and nitrogen, and where heterocyclyl is optionally substituted with halogen or C-Calkyl, -(C-Calkyl)Caryl, optionally substituted with halogen, or -(C-Calkyl)C-Cheteroaryl, 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 C-Calkyl; Rindependently represents halogen or OR. Other values of radicals are given in the invention formula.EFFECT: obtaining pharmaceutically accep