CYCLOALKYL NITRILE PYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS Russian patent published in 2018 - IPC C07D487/04 C07D519/00 A61K31/4162 A61K31/4427 A61K31/4709 A61K31/496 A61K31/5377 A61P11/06 A61P19/02 

FIELD: organic chemistry.

SUBSTANCE: invention relates to organic chemistry, specifically to a compound of formula I or a pharmaceutically acceptable salt thereof (I)

,

where A is selected from phenyl, isoindolinyl, quinolinyl, pyridinyl,

,

2,3-dihydro-1H-indenyl, benzothazolyl and 1,2,3,4-tetrahydroisoquinolinyl; n is 0, 1, 2, or 3; m is 0, 1, 2, or 3; p is 2, 3, or 4; R¹ is selected from: halogen, oxo(=O), C_1-6alkyl(oxy)_0-1(carbonyl)_0-1C_1-6alkyl, C_3-6cycloalkylC_0-6alkyl, heteroaryl (carbonyl)_0-1C_0-6alkyl, where heteroaryl is a 5–6 membered ring containing 1–3 heteroatoms selected from nitrogen, nitrogen and oxygen, and nitrogen and sulphur, (C_3-12)heterocycloalkyl(carbonyl)_0-1C_0-6alkyl, where the 3–12 membered heterocycloalkyl contains 1–2 heteroatoms selected from nitrogen, oxygen, nitrogen, sulphur, nitrogen and oxygen, and oxygen and sulphur, C_1-6alkyl(oxy)₁(carbonyl)₁aminoC_1-6alkyl, heteroaryl(carbonyl)₁aminoC_1-6alkyl, where heteroaryl is a 5–6 membered ring containing 1–2 heteroatoms selected from nitrogen and oxygen, C_0-6alkylamino(carbonyl)_0-1C_1-6alkyl, heteroarylamino(carbonyl)₁C_1-6alkyl, wherein heteroaryl is a 5-membered ring containing 1–2 heteroatoms selected from nitrogen, C_1-6alkylsulfonyl, (C_3-6)cycloheteroalkylsulfonylC_0-6alkyl, where cycloheteroalkyl contains 1–2 heteroatoms selected from nitrogen and oxygen, C_1-6alkylsulfonimidoyl, C_1-6alkylthioC_1-6alkyl, -CO₂H, -SO₂NH₂, -SO₂NH(C_1-6alkyl), -SO₂N(C_1-6alkyl)₂, -(C_1-6alkyl)OH, -C_1-6alkylalkoxy, cyano, and C_1-6haloalkyl; and where two R¹ may optionally bind to ring atoms to which they are attached to form a 3 to 6-membered ring; R² is selected from: halogen, C_1-6alkyl, (C_3-6)heterocycloalkyl, where heterocycloalkyl contains 1 nitrogen heteroatom, C_3-6cycloalkylC_1-6alkylamino, (C_1-6alkyl)_1-2amino, and hydroxy, where two R² may optionally be bound to a ring atom to which each is attached to form a 3–6 membered saturated ring; and where R¹ and R² each is optionally substituted with 1, 2, 3 or 4 substituents R³; R³ is independently selected from: halogen, C_1-6alkyl, phenyl, C_3-6cycloalkyl, piperidinyl, -CO₂(C_1-6alkyl), -CO₂H, amino, (C_1-6alkyl)_1-2amino, hydroxy, (C_1-6alkyl) OH, C_1-6alkoxyC_1-6alkyl, (C_1-6alkyl) cyano, C_1-6alkylsulfinylC_1-6alkyl, -O(C=O)C_1-6alkyl, oxo and C_1-6haloalkyl. Invention also relates to a pharmaceutical composition capable of inhibiting the activity of Janus kinases JAK1 and JAK2, and methods of treatment based on said compounds.

EFFECT: technical result: novel compounds are obtained, that can be used in medicine for treatment of arthritis, asthma and obstructive airways diseases, autoimmune diseases or disorders and cancer.

14 cl, 22 ex, 50 tbl