MACROCYCLIC LRRK2 KINASE INHIBITORS Russian patent published in 2017 - IPC C07D487/18 C07D498/18 C07D515/18 A61K31/504 A61K31/529 A61P25/16 A61P25/28 

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of Formula I:

,

which have the properties of LRRK2 kinase inhibitors. For Formula I, A1 and A2 are selected from C and N; where if A₁ is C, A₂ is N; and if A₂ is C, A₁ is N; R₁ is selected from -H, -halogen -C_1-6alkyl, -O-C_1-6alkyl, -(C=O)-R₄ and -CN; where each of the said C_1-6alkyls is optionally and independently substituted with -OH; R₂ is selected from -H and -C_1-6alkyl; where each of the said C_1-6alkyl is optionally and independently substituted with -OH, -OC-_1-6alkyl or -NR₁₃R₁₄; R₃ is selected from -H and -C_1-6alkyl; R₄ is -NR₁₇R₁₈; R₅ and R₇ are each independently selected from -H and -C_1-6alkyl; where each of the said C_1-6alkyls is optionally and independently substituted with -NR₂₃R₂₄; R₆ is selected from -SO₂-C_1-6alkyl, -(C=O)-OC_1-6alkyl, -(C=O)-C_1-6alkyl, -(C=O)-C_2-6alkenyl, -C_1-6alkyl-(C=O)-NR₃₁R₃₂, -SO₂-C_3-5cycloalkyl, -(C=O)-Het5, -(C=O)-Ar6, where each of the said C_1-6alkyls is optionally and independently substituted with with 1-3 substitutes gselected from -halogen, -OH, -OC_1-6alkyl, -Het5, -NR₂₅R₂₆; R₁₃, R₁₄, R₁₇, R₁₈, R₂₃, R₂₄, R₂₅, R₂₆, R₃₁ and R₃₂, each is independently selected from -H and -C_1-6alkyl; X₁ is selected from -OC_1-6alkylaryl, -SC_1-6alkylaryl, -NR₃-(C=O)-, -NR₃-(C=O)-C_1-6alkyl, -(C=O)-NR₃-C_1-6alkylaryl, -NR₃-C_1-6alkyl-, -C_1-6alkyl-NR₃-C_1-6alkyl-; where each the of said C_1-6alkyls is optionally and independently substituted with -C_1-6alkyl; X₂ is selected from -OC_1-6alkylaryl, -NR₂-FROM_1-6alkyl-; B is selected from -(C=O)-NR_5-, -NR₅-(C=O) -NR_7-, -SO₂-NR₅-, -NR₆-, -NR₅-(C=O)-O-; Ar6 is a 5-member aromatic heterocycle containing 1 or 2 heteroatoms selected from O and N; Het5 is a 5- or 6-member monocyclic heterocycle having 1 to 2 heteroatoms selected from O and N, wherein each heterocyclic ring is optionally and independently substituted with -C_1-6alkyl; each of the said -C_1-6alkyl is optionally substituted by halogen; each Z₁, Z₂, Z₃, Z₄ and Z₅ is selected from C. The invention also relates to the individual compounds, compound application, pharmaceutical composition, methods for prevention and/or treatment of neurological disorders.

EFFECT: new compounds of Formula I are obtained, having the properties of LRRK2 kinase inhibitors.

16 cl, 3 dwg, 4 tbl, 67 ex