FIELD: medicine.
SUBSTANCE: invention relates to an azatricyclic compound of formula
Formula (I),
where represents a double bond; one of X and Y is selected from N and the other from CR10; Z is N; each of R1, R2, R3, R4 and R5 is independently selected from H, halogen, C1-8 alkoxy; or R3 and R4 together with the carbon atom to which they are attached can form a 5-membered C 1-4 alkyl or halogen substituted or unsubstituted heteroaryl ring, the 5-membered heteroaryl ring containing 1, 2 or 3 heteroatoms independently selected from N, O or S; R6 is C1-8alkyl, phenyl, pyridyl, C3-8cycloalkyl, C5-6 heterocyclyl containing 1-2 ring heteroatoms selected from N and O; R6 is optionally substituted with R7; R7 is hydroxyl, halogen, C1-8alkyl, C1-8alkoxy, C3-8cycloalkyl, C3-8cycloalkyl substituted with C1-4alkyl, C5-10heterocyclyl containing 1-2 heteroatoms independently selected from nitrogen and oxygen, substituted with C1-4alkyl, C1-4alkylene-OH, -NR11R12, -oxo, - (CO) -C1-4alkyl, - (CO) -NR11R12, C1-4haloalkyl, C3-6cycloalkyl, C3-6cycloalkyl-OH, C4-6heterocyclyl containing 1-2 heteroatoms in the ring selected from nitrogen and oxygen, or C4-6heterocyclyl-C1-4alkyl containing 1-2 heteroatoms in the ring selected from N and O, C5-6heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen, C6heterocyclic carbonyl containing 1-2 nitrogen heteroatoms in the ring, substituted by C1-4 alkyl, -NR11R12, -NR11-C1-8alkylene-NR11R12, -C1-4alkylene-C5-6heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen, C1-4alkylene-C5-6heterocyclyl-C1-4alkyl containing 1-2 nitrogen heteroatoms in the ring, -C1-8alkoxy-C5-6heterocyclyl containing 1-2 heteroatoms in the ring, selected from nitrogen and oxygen, or in the case where R6 is phenyl, R7 is an unsubstituted C5-6 heterocyclic ring containing a nitrogen atom in the ring fused with R6; R10 is H, amino, C1-6alkyl, C3-8cycloalkyl; R10 is optionally substituted with R8; R8 is C1-8alkyl, C4-6heterocyclo-C1-6alkoxy substituted with - (CO) -C2-8alkenyl containing 1-2 heteroatoms selected from nitrogen and oxygen atoms in the ring, phenyl substituted with -NH- (CO) - C2-4 alkenyl or —NH- (CO) —C1-4 alkyl, C3-8 cycloalkyl, C5-6 heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen; mono-, bi- or spiro-C5-10heterocyclyl containing 1-2 nitrogen atoms; substituted by C1-4alkyl, C1-4alkyl (CO) -, C2-4alkenyl-C (O), C1-4alkyl (CO) -NH-, C2-4alkenyl-C (O) -NH- groups or - (CO) - C2-8 alkenyl-CN, mono-, bi- or spiroheterocyclyl containing 1-2 nitrogen atoms, -S (O2) C4-6heterocyclyl- (CO) -C2-4alkenyl, -NR11R12, substituted with C4-6 heterocyclyl- (CO) -C2-4 alkenyl containing 1-2 nitrogen heteroatoms in the ring, or -NR11R12; each of R11 and R12 is H, C1-8alkyl, which functions as an inhibitor of fibroblast growth factor receptors (FGFR) as well as a pharmaceutical composition based on it, and is used in treatment of diseases mediated by FGFR.
EFFECT: treatment of diseases mediated by FGFR.
34 cl, 3 dwg, 12 tbl, 148 ex
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Authors
Dates
2021-03-18—Published
2018-02-27—Filed