CA2948587C - Pyrazolopyridines and pyrazolopyrimidines - Google Patents
Pyrazolopyridines and pyrazolopyrimidines Download PDFInfo
- Publication number
- CA2948587C CA2948587C CA2948587A CA2948587A CA2948587C CA 2948587 C CA2948587 C CA 2948587C CA 2948587 A CA2948587 A CA 2948587A CA 2948587 A CA2948587 A CA 2948587A CA 2948587 C CA2948587 C CA 2948587C
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- Canada
- Prior art keywords
- amino
- methyl
- pyrazolo
- fluoro
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000005229 pyrazolopyridines Chemical class 0.000 title description 4
- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 403
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 181
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 151
- -1 C3-C8 cycloalkl Chemical group 0.000 claims abstract description 149
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 126
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 121
- 125000005843 halogen group Chemical group 0.000 claims abstract description 117
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 116
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 105
- 150000003839 salts Chemical class 0.000 claims abstract description 85
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 84
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 78
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 76
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 75
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 58
- 125000001424 substituent group Chemical group 0.000 claims abstract description 54
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 47
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 37
- 239000012453 solvate Substances 0.000 claims abstract description 35
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 32
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 30
- 208000006673 asthma Diseases 0.000 claims abstract description 25
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 25
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 22
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 10
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract description 10
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 323
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 178
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 94
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 47
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 35
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 8
- 230000005713 exacerbation Effects 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 206010063837 Reperfusion injury Diseases 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 6
- 230000009885 systemic effect Effects 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 206010048962 Brain oedema Diseases 0.000 claims description 3
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
- 206010006482 Bronchospasm Diseases 0.000 claims description 3
- 241000222122 Candida albicans Species 0.000 claims description 3
- 206010007134 Candida infections Diseases 0.000 claims description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 206010014824 Endotoxic shock Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
- 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000000112 Myalgia Diseases 0.000 claims description 3
- 206010028735 Nasal congestion Diseases 0.000 claims description 3
- 206010028741 Nasal inflammation Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000027771 Obstructive airways disease Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 3
- 208000011191 Pulmonary vascular disease Diseases 0.000 claims description 3
- 206010037660 Pyrexia Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038910 Retinitis Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 206010039094 Rhinitis perennial Diseases 0.000 claims description 3
- 208000036071 Rhinorrhea Diseases 0.000 claims description 3
- 206010039101 Rhinorrhoea Diseases 0.000 claims description 3
- 201000010001 Silicosis Diseases 0.000 claims description 3
- 208000006045 Spondylarthropathies Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 206010042496 Sunburn Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 206010046914 Vaginal infection Diseases 0.000 claims description 3
- 201000008100 Vaginitis Diseases 0.000 claims description 3
- 206010069351 acute lung injury Diseases 0.000 claims description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 3
- 208000006752 brain edema Diseases 0.000 claims description 3
- 201000009267 bronchiectasis Diseases 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 230000007885 bronchoconstriction Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 201000003984 candidiasis Diseases 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 208000007451 chronic bronchitis Diseases 0.000 claims description 3
- 201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims description 3
- 238000002651 drug therapy Methods 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 238000011010 flushing procedure Methods 0.000 claims description 3
- 230000035874 hyperreactivity Effects 0.000 claims description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 208000019423 liver disease Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 201000006938 muscular dystrophy Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 201000008383 nephritis Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 230000003959 neuroinflammation Effects 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 208000005987 polymyositis Diseases 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 201000005671 spondyloarthropathy Diseases 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- SOUUBYMKVDZNMX-UHFFFAOYSA-N N-[2-[[[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-(2-morpholin-4-ylethyl)amino]methyl]phenyl]-N-methylmethanesulfonamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)N(CCN1CCOCC1)CC1=C(C=CC=C1)N(S(=O)(=O)C)C)C=NN2 SOUUBYMKVDZNMX-UHFFFAOYSA-N 0.000 claims 2
- UROXANZIWZQDLE-UHFFFAOYSA-N 1-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-N,N-dimethylpyrrolidine-3-sulfonamide Chemical compound C(C)C1=C(C=CC(=C1)O)C1=CC2=C(C(=N1)N1CC(CC1)S(=O)(=O)N(C)C)C=NN2 UROXANZIWZQDLE-UHFFFAOYSA-N 0.000 claims 1
- 125000000134 2-(methylsulfanyl)ethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])[*] 0.000 claims 1
- ARRUYBCRZQEXRU-UHFFFAOYSA-N 2-[4-amino-2-[[2-[ethyl(ethylsulfonyl)amino]phenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]pyridin-3-yl]-2-iminoacetamide Chemical compound CCN(C1=CC=CC=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(=O)(=O)CC ARRUYBCRZQEXRU-UHFFFAOYSA-N 0.000 claims 1
- JSSUYMWUQFVPRG-UHFFFAOYSA-N 2-[4-amino-2-[[2-[ethyl(methylsulfonyl)amino]-5-methylphenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]pyridin-3-yl]-2-iminoacetamide Chemical compound CCN(C1=CC=C(C)C=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(C)(=O)=O JSSUYMWUQFVPRG-UHFFFAOYSA-N 0.000 claims 1
- TWLJIKCVSLJUIM-UHFFFAOYSA-N 2-[4-amino-2-[[5-chloro-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]pyridin-3-yl]-2-iminoacetamide Chemical compound CN(C1=CC=C(Cl)C=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(C)(=O)=O TWLJIKCVSLJUIM-UHFFFAOYSA-N 0.000 claims 1
- IJHPBWFDHMKENG-UHFFFAOYSA-N 2-[4-amino-6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-2-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)c1c(N)cc(nc1NCc1ccccc1N(C)S(C)(=O)=O)-c1cc(F)c(O)cc1C1CC1 IJHPBWFDHMKENG-UHFFFAOYSA-N 0.000 claims 1
- ZNVOURRPUATFRP-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[2-[2-hydroxyethyl(methylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-iminoacetamide Chemical compound CS(=O)(=O)N(CCO)C1=CC=CC=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F ZNVOURRPUATFRP-UHFFFAOYSA-N 0.000 claims 1
- FIUWLGOGPXZKNM-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)C1=C(NCC2=CC=CN=C2N(C)S(C)(=O)=O)N=C(C=C1N)C1=CC(F)=C(O)C=C1CC(F)(F)F FIUWLGOGPXZKNM-UHFFFAOYSA-N 0.000 claims 1
- FBOHXIKPCPPBCA-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[2-[methyl(pyridin-3-ylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-iminoacetamide Chemical compound CN(C1=CC=CC=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(=O)(=O)C1=CC=CN=C1 FBOHXIKPCPPBCA-UHFFFAOYSA-N 0.000 claims 1
- BOUSUZDOWGVFOY-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)c1c(N)cc(nc1NCc1nccnc1N(C)S(C)(=O)=O)-c1cc(F)c(O)cc1CC(F)(F)F BOUSUZDOWGVFOY-UHFFFAOYSA-N 0.000 claims 1
- ZOLFPEWMVUHAGI-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[5-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)c1c(N)cc(nc1NCc1cc(O)ccc1N(C)S(C)(=O)=O)-c1cc(F)c(O)cc1CC(F)(F)F ZOLFPEWMVUHAGI-UHFFFAOYSA-N 0.000 claims 1
- YEDJPXKZPPPMNF-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[5-hydroxy-2-[methyl(pyridin-3-ylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)c1c(N)cc(nc1NCc1cc(O)ccc1N(C)S(=O)(=O)c1cccnc1)-c1cc(F)c(O)cc1CC(F)(F)F YEDJPXKZPPPMNF-UHFFFAOYSA-N 0.000 claims 1
- RAOSMRQNSKDBMX-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[5-methyl-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-imino-N-methylacetamide Chemical compound CNC(=O)C(=N)c1c(N)cc(nc1NCc1cc(C)ccc1N(C)S(C)(=O)=O)-c1cc(F)c(O)cc1CC(F)(F)F RAOSMRQNSKDBMX-UHFFFAOYSA-N 0.000 claims 1
- WKRKSQPZCXXBLG-UHFFFAOYSA-N 2-[4-amino-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-2-[[5-methyl-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]pyridin-3-yl]-2-iminoacetamide Chemical compound CN(C1=CC=C(C)C=C1CNC1=C(C(=N)C(N)=O)C(N)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(C)(=O)=O WKRKSQPZCXXBLG-UHFFFAOYSA-N 0.000 claims 1
- NDNPKPHRUSXHAY-UHFFFAOYSA-N 2-[4-amino-6-[[2-[benzenesulfonyl(methyl)amino]phenyl]methylamino]-2-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]pyrimidin-5-yl]-2-iminoacetamide Chemical compound CN(C1=CC=CC=C1CNC1=C(C(=N)C(N)=O)C(N)=NC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(=O)(=O)C1=CC=CC=C1 NDNPKPHRUSXHAY-UHFFFAOYSA-N 0.000 claims 1
- ZLZITJPTLFZCBE-UHFFFAOYSA-N 2-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-N-(2-pyrrolidin-1-ylethyl)-3,4-dihydro-1H-isoquinoline-7-sulfonamide Chemical compound C(C)C1=C(C=CC(=C1)O)C1=CC2=C(C(=N1)N1CC3=CC(=CC=C3CC1)S(=O)(=O)NCCN1CCCC1)C=NN2 ZLZITJPTLFZCBE-UHFFFAOYSA-N 0.000 claims 1
- AXUAAROKDDFUCI-UHFFFAOYSA-N 2-fluoro-4-[4-(2-methylpropylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-5-(2,2,2-trifluoroethyl)phenol Chemical compound FC1=C(C=C(C(=C1)C1=NC(=C2C(=N1)NN=C2)NCC(C)C)CC(F)(F)F)O AXUAAROKDDFUCI-UHFFFAOYSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- CWWJGUPPMFHHBU-UHFFFAOYSA-N 3-ethyl-4-[4-(4-methoxypiperidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC(CC2)OC)=C2C=NNC2=C1 CWWJGUPPMFHHBU-UHFFFAOYSA-N 0.000 claims 1
- WBJKFNOYTALWJK-UHFFFAOYSA-N 3-ethyl-4-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=CC(F)=CC=C3C2)=C2C=NNC2=C1 WBJKFNOYTALWJK-UHFFFAOYSA-N 0.000 claims 1
- COIIDULXTXBYHQ-UHFFFAOYSA-N 3-ethyl-4-[4-(6-methoxy-7-phenylmethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=C(C2)C=C(OCC2=CC=CC=C2)C(OC)=C3)=C2C=NNC2=C1 COIIDULXTXBYHQ-UHFFFAOYSA-N 0.000 claims 1
- CMXPYUOPFJEEGA-UHFFFAOYSA-N 3-ethyl-4-[4-(8-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=C(C2)C(OC)=CC=C3)=C2C=NNC2=C1 CMXPYUOPFJEEGA-UHFFFAOYSA-N 0.000 claims 1
- IFOCLNIXUQUORY-UHFFFAOYSA-N 3-ethyl-4-[4-[6-(2-methoxyethoxy)-3,4-dihydro-1H-isoquinolin-2-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl]phenol Chemical compound CCC1=CC(O)=CC=C1C1=NC(N2CCC3=CC(OCCOC)=CC=C3C2)=C2C=NNC2=C1 IFOCLNIXUQUORY-UHFFFAOYSA-N 0.000 claims 1
- YDHPBDFTCLQXLO-UHFFFAOYSA-N 4-(cyclopentylmethylamino)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CCCC1)CNC1=NC(=CC2=C1C(=NN2)C(=O)NC)C2=C(C=C(C(=C2)F)O)CC YDHPBDFTCLQXLO-UHFFFAOYSA-N 0.000 claims 1
- FRFUERGTAKOJMH-UHFFFAOYSA-N 4-(cyclopentylmethylamino)-6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CCCC1)CNC1=NC(=CC2=C1C(=NN2)C(=O)NC)C2=C(C=C(C(=C2)F)O)CC(F)(F)F FRFUERGTAKOJMH-UHFFFAOYSA-N 0.000 claims 1
- YKNVIPJBLFUUQP-UHFFFAOYSA-N 4-[2-[4-(benzenesulfonamido)phenyl]ethylamino]-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCCC1=CC=C(C=C1)NS(=O)(=O)C1=CC=CC=C1)C(=NN2)C(=O)NC YKNVIPJBLFUUQP-UHFFFAOYSA-N 0.000 claims 1
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- VFQLTBRWKTYVKQ-UHFFFAOYSA-N 6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CC1)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)N VFQLTBRWKTYVKQ-UHFFFAOYSA-N 0.000 claims 1
- COAUOAVYHZTIMG-UHFFFAOYSA-N 6-(2-cyclopropyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C1(CC1)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC=1C(=NC=CC1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC COAUOAVYHZTIMG-UHFFFAOYSA-N 0.000 claims 1
- VMCSVMRRMNTTNV-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[2-(4-hydroxyphenyl)ethylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCCC1=CC=C(C=C1)O)C(=NN2)C(=O)NC VMCSVMRRMNTTNV-UHFFFAOYSA-N 0.000 claims 1
- LNRYTDNWEWDQCY-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[2-[ethyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)CC)C(=NN2)C(=O)NC LNRYTDNWEWDQCY-UHFFFAOYSA-N 0.000 claims 1
- YFVIZNVKXROZSI-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[2-[ethylsulfonyl(methyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(C)S(=O)(=O)CC)C(=NN2)C(=O)NC YFVIZNVKXROZSI-UHFFFAOYSA-N 0.000 claims 1
- YSFORCCNHDVKJO-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[2-fluoro-6-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1N(S(=O)(=O)C)C)F)C(=NN2)C(=O)NC YSFORCCNHDVKJO-UHFFFAOYSA-N 0.000 claims 1
- NBQIWMZOJLUOPZ-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[4-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=C(C=C1)O)N(S(=O)(=O)C)C)C(=NN2)C(=O)N NBQIWMZOJLUOPZ-UHFFFAOYSA-N 0.000 claims 1
- LGAVUEXTUHVZEO-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[4-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=C(C=C1)O)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC LGAVUEXTUHVZEO-UHFFFAOYSA-N 0.000 claims 1
- SGYVXZSTJKNPNV-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[5-fluoro-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC(=C1)F)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC SGYVXZSTJKNPNV-UHFFFAOYSA-N 0.000 claims 1
- IPHYEMRMCZKRFY-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-4-[[5-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC(=C1)O)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC IPHYEMRMCZKRFY-UHFFFAOYSA-N 0.000 claims 1
- SLDNTHWIALNKOG-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-(2-methylpropylamino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC(C)C)C(=NN2)C(=O)NC SLDNTHWIALNKOG-UHFFFAOYSA-N 0.000 claims 1
- GTGNVCWEJRBFQX-CQSZACIVSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[(1R)-1-[2-[methyl(methylsulfonyl)amino]phenyl]ethyl]amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)N[C@H](C)C1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC GTGNVCWEJRBFQX-CQSZACIVSA-N 0.000 claims 1
- GTGNVCWEJRBFQX-AWEZNQCLSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[(1S)-1-[2-[methyl(methylsulfonyl)amino]phenyl]ethyl]amino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)N[C@@H](C)C1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC GTGNVCWEJRBFQX-AWEZNQCLSA-N 0.000 claims 1
- KZIWMYSRNRBZJV-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC KZIWMYSRNRBZJV-UHFFFAOYSA-N 0.000 claims 1
- IOCOZGHPXHMJEK-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=NC(=C2C(=N1)NN=C2C(=O)NC)NCC2=C(C=CC=C2)N(S(=O)(=O)C)C IOCOZGHPXHMJEK-UHFFFAOYSA-N 0.000 claims 1
- HUKBNTKAEHEDEF-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[2-[methyl(sulfamoyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(N)(=O)=O)C)C(=NN2)C(=O)NC HUKBNTKAEHEDEF-UHFFFAOYSA-N 0.000 claims 1
- GLHCQBBMHMUVQE-UHFFFAOYSA-N 6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-N-methyl-4-[[5-methyl-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(C)C1=C(C=C(C(=C1)O)F)C1=CC2=C(C(=N1)NCC1=C(C=CC(=C1)C)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC GLHCQBBMHMUVQE-UHFFFAOYSA-N 0.000 claims 1
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- IZAMCANGXNJSFB-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl(3-morpholin-4-ylpropylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)CCCN1CCOCC1)C)C(=NN2)C(=O)N)CC(F)(F)F)O IZAMCANGXNJSFB-UHFFFAOYSA-N 0.000 claims 1
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- RGWGGKUGOBJLKL-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC=1C(=NC=CC1)N(S(=O)(=O)C)C)C(=NN2)C(=O)N)CC(F)(F)F)O RGWGGKUGOBJLKL-UHFFFAOYSA-N 0.000 claims 1
- ABQICQLAAZYVLN-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl-(6-methylpyridin-3-yl)sulfonylamino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C=1C=NC(=CC1)C)C)C(=NN2)C(=O)N)CC(F)(F)F)O ABQICQLAAZYVLN-UHFFFAOYSA-N 0.000 claims 1
- ROLXISZVVXDGHN-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-[methyl-(6-morpholin-4-ylpyridin-3-yl)sulfonylamino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C=1C=NC(=CC1)N1CCOCC1)C)C(=NN2)C(=O)N)CC(F)(F)F)O ROLXISZVVXDGHN-UHFFFAOYSA-N 0.000 claims 1
- BZENPXKJXYPNIH-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[2-fluoro-6-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1N(S(=O)(=O)C)C)F)C(=NN2)C(=O)NC)CC(F)(F)F)O BZENPXKJXYPNIH-UHFFFAOYSA-N 0.000 claims 1
- XGUJFKWJNPKJFG-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[4-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=C(C=C1)O)N(S(=O)(=O)C)C)C(=NN2)C(=O)N)CC(F)(F)F)O XGUJFKWJNPKJFG-UHFFFAOYSA-N 0.000 claims 1
- FALMJPFUCBVHKL-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[4-hydroxy-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=C(C=C1)O)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O FALMJPFUCBVHKL-UHFFFAOYSA-N 0.000 claims 1
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- YFJCJTRBQHCXLT-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[5-fluoro-2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-N-methyl-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound FC=1C=CC(=C(CNC2=C3C(=NC(=N2)C2=C(C=C(C(=C2)F)O)CC(F)(F)F)NN=C3C(=O)NC)C1)N(S(=O)(=O)C)C YFJCJTRBQHCXLT-UHFFFAOYSA-N 0.000 claims 1
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- DMDLUSXJFJBYLZ-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-4-[[5-methyl-2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound CN(C1=NC=C(C)C=C1CNC1=C2C(NN=C2C(N)=O)=CC(=N1)C1=CC(F)=C(O)C=C1CC(F)(F)F)S(C)(=O)=O DMDLUSXJFJBYLZ-UHFFFAOYSA-N 0.000 claims 1
- SVRYJVCODHDAJL-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-(2-methylpropylamino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC(C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O SVRYJVCODHDAJL-UHFFFAOYSA-N 0.000 claims 1
- ALGHXSFRWUBSAW-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-(sulfamoylmethyl)phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)CS(N)(=O)=O)C(=NN2)C(=O)NC)CC(F)(F)F)O ALGHXSFRWUBSAW-UHFFFAOYSA-N 0.000 claims 1
- AELCQCOWVRHKDK-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl(1H-pyrazol-4-ylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C=1C=NNC1)C)C(=NN2)C(=O)NC)CC(F)(F)F)O AELCQCOWVRHKDK-UHFFFAOYSA-N 0.000 claims 1
- YTDNMQPIDMGVDR-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl(methylsulfamoyl)amino]phenyl]methylamino]-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=NC(=C2C(=N1)NN=C2C(=O)NC)NCC2=C(C=CC=C2)N(S(NC)(=O)=O)C)CC(F)(F)F)O YTDNMQPIDMGVDR-UHFFFAOYSA-N 0.000 claims 1
- YJSHIGLIYUPAIT-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl(methylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O YJSHIGLIYUPAIT-UHFFFAOYSA-N 0.000 claims 1
- BBQPXRWWGFVMOX-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl(pyridin-3-ylsulfonyl)amino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C=1C=NC=CC1)C)C(=NN2)C(=O)NC)CC(F)(F)F)O BBQPXRWWGFVMOX-UHFFFAOYSA-N 0.000 claims 1
- BRQCTFOAORTYKM-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl(sulfamoyl)amino]phenyl]methylamino]-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=NC(=C2C(=N1)NN=C2C(=O)NC)NCC2=C(C=CC=C2)N(S(N)(=O)=O)C)CC(F)(F)F)O BRQCTFOAORTYKM-UHFFFAOYSA-N 0.000 claims 1
- CVAKSHSZMWJDKV-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[2-[methyl-(6-methylpyridin-3-yl)sulfonylamino]phenyl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C=1C=NC(=CC1)C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O CVAKSHSZMWJDKV-UHFFFAOYSA-N 0.000 claims 1
- CNLKMAASBAEKQE-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-2H-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=NC(=C2C(=N1)NN=C2C(=O)NC)NCC2=NC=CN=C2N(S(=O)(=O)C)C)CC(F)(F)F)O CNLKMAASBAEKQE-UHFFFAOYSA-N 0.000 claims 1
- ILQBVOMILHZYSA-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[4-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC=1C=NC=CC1N(S(=O)(=O)C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O ILQBVOMILHZYSA-UHFFFAOYSA-N 0.000 claims 1
- IASHJKDORLDCHI-UHFFFAOYSA-N 6-[5-fluoro-4-hydroxy-2-(2,2,2-trifluoroethyl)phenyl]-N-methyl-4-[[5-methyl-2-[methyl(methylsulfonyl)amino]pyridin-3-yl]methylamino]-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound FC=1C(=CC(=C(C1)C1=CC2=C(C(=N1)NCC=1C(=NC=C(C1)C)N(S(=O)(=O)C)C)C(=NN2)C(=O)NC)CC(F)(F)F)O IASHJKDORLDCHI-UHFFFAOYSA-N 0.000 claims 1
- AFPLYFPFUPHZMR-UHFFFAOYSA-N N-[2-[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]-3,4-dihydro-1H-isoquinolin-5-yl]methanesulfonamide formic acid Chemical compound C(=O)O.C(C)C1=C(C=CC(=C1)O)C1=CC2=C(C(=N1)N1CC3=CC=CC(=C3CC1)NS(=O)(=O)C)C=NN2 AFPLYFPFUPHZMR-UHFFFAOYSA-N 0.000 claims 1
- WZULFGLWRRTFDD-UHFFFAOYSA-N N-[2-[[[3-(4,5-dimethyl-1H-imidazol-2-yl)-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino]methyl]phenyl]-N-methylmethanesulfonamide Chemical compound CC=1N=C(NC1C)C1=NNC2=C1C(=NC(=C2)C2=C(C=C(C(=C2)F)O)CC)NCC2=C(C=CC=C2)N(S(=O)(=O)C)C WZULFGLWRRTFDD-UHFFFAOYSA-N 0.000 claims 1
- NXNUCUDLNXMRTO-UHFFFAOYSA-N N-[2-[[[4-amino-6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-3-methanimidoylpyridin-2-yl]-[2-(3,4-dimethoxyphenyl)ethyl]amino]methyl]phenyl]-N-methylmethanesulfonamide Chemical compound CCC1=CC(O)=C(F)C=C1C1=NC(N(CCC2=CC(OC)=C(OC)C=C2)CC2=CC=CC=C2N(C)S(C)(=O)=O)=C(C=N)C(N)=C1 NXNUCUDLNXMRTO-UHFFFAOYSA-N 0.000 claims 1
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- IYPWKCDAGXWKTK-UHFFFAOYSA-N N-[2-[[[6-(2-ethyl-4-hydroxyphenyl)-1H-pyrazolo[4,3-c]pyridin-4-yl]amino]methyl]phenyl]-N-methylmethanesulfonamide hydrochloride Chemical compound Cl.C(C)C1=C(C=CC(=C1)O)C1=CC2=C(C(=N1)NCC1=C(C=CC=C1)N(S(=O)(=O)C)C)C=NN2 IYPWKCDAGXWKTK-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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| US9403810B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
| MD20160121A2 (ro) | 2014-05-14 | 2017-05-31 | Pfizer Inc. | Pirazolopiridine şi pirazolopirimidine |
| US10556901B2 (en) | 2015-11-03 | 2020-02-11 | Topivert Pharma Limited | 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine and 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepine derivatives as Janus kinase inhibitors |
| MY195427A (en) | 2015-11-03 | 2023-01-20 | Theravance Biopharma R&D Ip Llc | Jak Kinase Inhibitor Compounds for Treatment of Respiratory Disease |
| ES2864035T3 (es) | 2015-11-03 | 2021-10-13 | Topivert Pharma Ltd | Derivados de 4,5,6,7-tetrahidro-1h-imidazo[4,5-c]piridina y 1,4,5,6,7,8-hexahidroimidazo[4,5-d]azepina como inhibidores de la quinasa janus |
| AU2018231032B2 (en) | 2017-03-09 | 2021-08-19 | Theravance Biopharma R&D Ip, Llc | JAK inhibitors containing a 4-membered heterocyclic amide |
| RU2764979C2 (ru) | 2017-05-01 | 2022-01-24 | ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи | Способы лечения с использованием соединения-ингибитора jak |
| WO2018204236A1 (en) | 2017-05-01 | 2018-11-08 | Theravance Biopharma R&D Ip, Llc | Crystalline forms of a jak inhibitor compound |
| AR111495A1 (es) | 2017-05-01 | 2019-07-17 | Theravance Biopharma R&D Ip Llc | Compuestos de imidazo-piperidina fusionada como inhibidores de jak |
| KR20200036004A (ko) | 2017-08-01 | 2020-04-06 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 키나아제 억제제로서 피라졸로 및 트리아졸로 비시클릭 화합물 |
| AU2018360059B2 (en) | 2017-11-03 | 2023-07-13 | Aclaris Therapeutics, Inc. | Substituted pyrrolopyrimidine JAK inhibitors and methods of making and using the same |
| AU2019317625B2 (en) | 2018-08-10 | 2025-02-27 | Aclaris Therapeutics, Inc. | Pyrrolopyrimidine ITK inhibitors |
| CN110833555B (zh) * | 2018-08-15 | 2023-03-24 | 广西梧州制药（集团）股份有限公司 | 吡唑并嘧啶衍生物在治疗溃疡性结肠炎的用途 |
| ES2955717T3 (es) | 2018-09-04 | 2023-12-05 | Theravance Biopharma R&D Ip Llc | Amidas heterocíclicas de 5 a 7 elementos como inhibidores de JAK |
| WO2020051135A1 (en) | 2018-09-04 | 2020-03-12 | Theravance Biopharma R&D Ip, Llc | Process for preparing jak inhibitors and intermediates thereof |
| DK3837258T3 (da) | 2018-09-04 | 2024-07-22 | Theravance Biopharma R&D Ip Llc | Dimethyl amino azetidine amides as jak inhibitors |
| JP2022506111A (ja) | 2018-10-29 | 2022-01-17 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｊａｋ阻害剤としての２－アザビシクロヘキサン化合物 |
| US10851102B2 (en) | 2019-01-23 | 2020-12-01 | Theravance Biopharma R&D Ip, Llc | Imidazole and triazole containing bicyclic compounds as JAK inhibitors |
| AU2020228799B2 (en) | 2019-02-25 | 2024-12-05 | Henan Medinno Pharmaceutical Technology Co., Ltd. | JAK inhibitor compound and use thereof |
| CN114075200A (zh) * | 2020-08-14 | 2022-02-22 | 河南迈英诺医药科技有限公司 | 用于治疗重症肺炎的jak抑制剂化合物 |
| CN114075199A (zh) * | 2020-08-14 | 2022-02-22 | 河南迈英诺医药科技有限公司 | Jak抑制剂化合物及其用途 |
| US11420966B2 (en) | 2019-05-02 | 2022-08-23 | Aclaris Therapeutics, Inc. | Substituted pyrrolopyridines as JAK inhibitors |
| WO2021022178A1 (en) * | 2019-07-31 | 2021-02-04 | Aclaris Therapeutics, Inc. | Substituted sulfonamide pyrrolopyridines as jak inhibitors |
| WO2021136345A1 (zh) * | 2019-12-30 | 2021-07-08 | 路良 | Jak抑制剂化合物及其用途 |
| TWI885039B (zh) | 2020-01-13 | 2025-06-01 | 美商邊際分析公司 | 經取代吡唑并嘧啶及其用途 |
| CN113101975B (zh) * | 2020-01-13 | 2022-04-22 | 万华化学集团股份有限公司 | 一种多膦配体催化剂体系及其在乙烯齐聚反应的应用 |
| TW202144343A (zh) | 2020-03-02 | 2021-12-01 | 美商施萬生物製藥研發 Ip有限責任公司 | Jak抑制劑化合物之結晶水合物 |
| CN111548269B (zh) * | 2020-04-29 | 2023-10-27 | 兰州大学 | 一种二芳基甲烷结构化合物的制备方法 |
| GB202010408D0 (en) * | 2020-07-07 | 2020-08-19 | Reviral Ltd | Pharmaceutical compounds |
| WO2022053651A2 (en) | 2020-09-10 | 2022-03-17 | Precirix N.V. | Antibody fragment against fap |
| TW202317550A (zh) | 2021-06-25 | 2023-05-01 | 美商施萬生物製藥研發 Ip有限責任公司 | 作為jak抑制劑之咪唑吲唑化合物 |
| CN115557947B (zh) * | 2021-07-02 | 2024-04-02 | 成都百裕制药股份有限公司 | 吡唑并[4,3-c]吡啶衍生物及其在医药上的应用 |
| CN113480543B (zh) * | 2021-07-07 | 2022-05-17 | 无锡市第二人民医院 | 2,6,8-多取代咪唑并[1,2-a]吡嗪及其合成方法和应用 |
| WO2023203135A1 (en) | 2022-04-22 | 2023-10-26 | Precirix N.V. | Improved radiolabelled antibody |
| WO2023213801A1 (en) | 2022-05-02 | 2023-11-09 | Precirix N.V. | Pre-targeting |
| WO2025217560A1 (en) * | 2024-04-12 | 2025-10-16 | Theravance Biopharma R&D Ip, Llc | Triazolo indazole compounds as jak inhibitors |
Family Cites Families (21)
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| US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
| US20060223826A1 (en) | 2002-11-19 | 2006-10-05 | Takeda Pharmaceutical Company Limited Intellectual Property Department | Indole derivatives as somatostatin agonists or antagonists |
| US20080234262A1 (en) * | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| BRPI0810411B8 (pt) | 2007-04-18 | 2021-05-25 | Pfizer Prod Inc | derivados de sulfonil amida para o tratamento de crescimento celular anormal, seu sos, bem como composição farmacêutica |
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| CA2711759A1 (en) * | 2008-01-30 | 2009-08-06 | Genentech, Inc. | Pyrazolopyrimidine pi3k inhibitor compounds and methods of use |
| JP5502858B2 (ja) * | 2008-06-05 | 2014-05-28 | グラクソ グループ リミテッド | Ｐｉ３キナーゼの阻害剤として有用な４−カルボキサミドインダゾール誘導体 |
| WO2009153261A1 (en) * | 2008-06-18 | 2009-12-23 | Solvay Pharmaceuticals Gmbh | HYDROXYPHENYL-SUBSTITUTED PYRROLO[2,3d]PYRIMIDINE DERIVATIVES, PROCESSES AND INTERMEDIATE PRODUCTS FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING THESE COMPOUNDS |
| WO2010058846A1 (ja) | 2008-11-21 | 2010-05-27 | アステラス製薬株式会社 | ４，６-ジアミノニコチンアミド化合物 |
| RU2011142182A (ru) * | 2009-03-19 | 2013-04-27 | Медикал Рисерч Каунсил Текнолоджи | Соединения |
| WO2012045195A1 (en) | 2010-10-09 | 2012-04-12 | Abbott Laboratories | Pyrrolopyrimidines as fak and alk inhibiters for treatment of cancers and other diseases |
| US8575336B2 (en) | 2011-07-27 | 2013-11-05 | Pfizer Limited | Indazoles |
| MD20160121A2 (ro) | 2014-05-14 | 2017-05-31 | Pfizer Inc. | Pirazolopiridine şi pirazolopirimidine |
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