Patent RU-2745035-C1 (RU)
Inventor: XU XIAOFENG
IPC: C07D487/14
Filed: 2018-02-27
Granted: 2021-03-18
Abstract: 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 CR 10 ; Z is N; each of R 1 , R 2 , R 3 , R 4  and R 5  is independently selected from H, halogen, C 1-8  alkoxy; or R 3  and R 4  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; R 6  is C 1-8 alkyl, phenyl, pyridyl, C 3-8 cycloalkyl, C 5-6  heterocyclyl containing 1-2 ring heteroatoms selected from N and O; R 6  is optionally substituted with R 7 ; R 7  is hydroxyl, halogen, C 1-8 alkyl, C 1-8 alkoxy, C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted with C 1-4 alkyl, C 5-10 heterocyclyl containing 1-2 heteroatoms independently selected from nitrogen and oxygen, substituted with C 1-4 alkyl,  C1-4 alkylene-OH, -NR 11 R 12 , -oxo, - (CO) -C 1-4 alkyl, - (CO) -NR 11 R 12 , C 1-4 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-OH, C 4-6 heterocyclyl containing 1-2 heteroatoms in the ring selected from nitrogen and oxygen, or C 4-6 heterocyclyl-C 1-4 alkyl containing 1-2 heteroatoms in the ring selected from N and O, C 5-6 heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen, C 6 heterocyclic carbonyl containing 1-2 nitrogen heteroatoms in the ring, substituted by C 1-4  alkyl, -NR 11 R 12 , -NR 11 -C 1-8 alkylene-NR 11 R 12 , -C 1-4 alkylene-C 5-6 heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen, C 1-4 alkylene-C 5-6 heterocyclyl-C 1-4 alkyl containing 1-2 nitrogen heteroatoms in the ring, -C 1-8 alkoxy-C 5-6 heterocyclyl containing 1-2 heteroatoms in the ring, selected from nitrogen and oxygen, or in the case where R 6  is phenyl, R 7  is an unsubstituted C 5-6  heterocyclic ring containing a nitrogen atom in the ring fused with R 6 ; R 10  is H, amino, C 1-6 alkyl, C 3-8 cycloalkyl; R 10  is optionally substituted with R 8 ; R 8  is C 1-8 alkyl, C 4-6 heterocyclo-C 1-6 alkoxy substituted with - (CO) -C 2-8 alkenyl containing 1-2 heteroatoms selected from nitrogen and oxygen atoms in the ring, phenyl substituted with -NH- (CO) - C 2-4  alkenyl or —NH- (CO) —C 1-4  alkyl, C 3-8  cycloalkyl, C 5-6  heterocyclyl containing 1-2 heteroatoms selected from nitrogen and oxygen; mono-, bi- or spiro-C 5-10 heterocyclyl containing 1-2 nitrogen atoms; substituted by C 1-4 alkyl, C 1-4 alkyl (CO) -, C 2-4 alkenyl-C (O), C 1-4 alkyl (CO) -NH-, C 2-4 alkenyl-C (O) -NH- groups or - (CO) - C 2-8  alkenyl-CN, mono-, bi- or spiroheterocyclyl containing 1-2 nitrogen atoms, -S (O2) C 4-6 heterocyclyl- (CO) -C 2-4 alkenyl, -NR 11 R 12 , substituted with C 4-6  heterocyclyl- (CO) -C 2-4  alkenyl containing 1-2 nitrogen heteroatoms in the ring, or -NR 11 R 12 ; each of R 11  and R 12  is H, C 1-8 alkyl, 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