KR20170002623A - 피라졸로피리딘 및 피라졸로피리미딘 - Google Patents
피라졸로피리딘 및 피라졸로피리미딘 Download PDFInfo
- Publication number
- KR20170002623A KR20170002623A KR1020167034627A KR20167034627A KR20170002623A KR 20170002623 A KR20170002623 A KR 20170002623A KR 1020167034627 A KR1020167034627 A KR 1020167034627A KR 20167034627 A KR20167034627 A KR 20167034627A KR 20170002623 A KR20170002623 A KR 20170002623A
- Authority
- KR
- South Korea
- Prior art keywords
- amino
- methyl
- pyrazolo
- phenyl
- alkyl
- 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.)
- Ceased
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- APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 3
- 150000005229 pyrazolopyridines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 400
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims abstract description 359
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 301
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 177
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 140
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 122
- 125000005843 halogen group Chemical group 0.000 claims abstract description 118
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 96
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 91
- 150000003839 salts Chemical class 0.000 claims abstract description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 79
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 76
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 76
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 70
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 48
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 47
- 125000001424 substituent group Chemical group 0.000 claims abstract description 45
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 44
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 41
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- 239000012453 solvate Substances 0.000 claims abstract description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 28
- 208000006673 asthma Diseases 0.000 claims abstract description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 20
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 18
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 314
- 238000000034 method Methods 0.000 claims description 137
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 136
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 114
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 101
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 85
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 77
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 62
- 235000005152 nicotinamide Nutrition 0.000 claims description 57
- 239000011570 nicotinamide Substances 0.000 claims description 57
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 48
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 14
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 13
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 11
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 11
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 8
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 206010040070 Septic Shock Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 206010028735 Nasal congestion Diseases 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010063837 Reperfusion injury Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 208000017442 Retinal disease Diseases 0.000 claims description 4
- 206010038923 Retinopathy Diseases 0.000 claims description 4
- 208000036142 Viral infection Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- UHNHTTIUNATJKL-UHFFFAOYSA-N n-methylmethanesulfonamide Chemical compound CNS(C)(=O)=O UHNHTTIUNATJKL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 3
- HYBUYRZXNAZTPJ-UHFFFAOYSA-N 2h-pyrazolo[3,4-d]pyrimidine-3-carboxamide Chemical compound N1=CN=CC2=C(C(=O)N)NN=C21 HYBUYRZXNAZTPJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010048962 Brain oedema Diseases 0.000 claims description 3
- 208000031229 Cardiomyopathies 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
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 206010014824 Endotoxic shock Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 3
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000000112 Myalgia Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- 208000011191 Pulmonary vascular disease Diseases 0.000 claims description 3
- 208000006045 Spondylarthropathies Diseases 0.000 claims description 3
- 206010042496 Sunburn 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
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 206010069351 acute lung injury Diseases 0.000 claims description 3
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 3
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 3
- 208000006752 brain edema Diseases 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- XLZLNCSZYWPDRJ-UHFFFAOYSA-N ethanesulfonamide;hydrochloride Chemical compound Cl.CCS(N)(=O)=O XLZLNCSZYWPDRJ-UHFFFAOYSA-N 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 208000019423 liver disease Diseases 0.000 claims description 3
- USJUUYYGHABIBU-UHFFFAOYSA-N methanesulfonamide;hydrochloride Chemical compound Cl.CS(N)(=O)=O USJUUYYGHABIBU-UHFFFAOYSA-N 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 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
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 201000009890 sinusitis Diseases 0.000 claims description 3
- 201000005671 spondyloarthropathy Diseases 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- FHHZSTXNBSIOAQ-UHFFFAOYSA-N 4-[4-(butylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-2-fluoro-5-(2,2,2-trifluoroethyl)phenol Chemical compound C(CCC)NC1=C2C(=NC(=N1)C1=CC(=C(C=C1CC(F)(F)F)O)F)NN=C2 FHHZSTXNBSIOAQ-UHFFFAOYSA-N 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 2
- 206010006482 Bronchospasm Diseases 0.000 claims description 2
- OYHODLAPGNSRGG-UHFFFAOYSA-N C(=O)O.C(#N)C1=CC=CC=C1 Chemical compound C(=O)O.C(#N)C1=CC=CC=C1 OYHODLAPGNSRGG-UHFFFAOYSA-N 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 2
- 208000010412 Glaucoma Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 2
- CKSBCGAQBBVFNI-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 Chemical compound CS(=O)(=O)NC1=C2CCN(CC2=CC=C1)C1=NC(=CC2=C1C=NN2)C1=C(C=C(C=C1)O)CC CKSBCGAQBBVFNI-UHFFFAOYSA-N 0.000 claims description 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
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- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 206010046914 Vaginal infection Diseases 0.000 claims description 2
- 201000008100 Vaginitis Diseases 0.000 claims description 2
- PAEPZXVORXSCRP-UHFFFAOYSA-N [3-ethyl-4-[4-(3-phenoxyazetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]phenyl] formate Chemical compound C(=O)OC1=CC(=C(C=C1)C1=CC2=C(C(=N1)N1CC(C1)OC1=CC=CC=C1)C=NN2)CC PAEPZXVORXSCRP-UHFFFAOYSA-N 0.000 claims description 2
- RKXXPUWGONIRST-UHFFFAOYSA-N [3-ethyl-4-[4-[2-(4-phenylphenyl)ethylamino]-1H-pyrazolo[4,3-c]pyridin-6-yl]phenyl] formate Chemical compound C(=O)OC1=CC(=C(C=C1)C1=CC2=C(C(=N1)NCCC1=CC=C(C=C1)C1=CC=CC=C1)C=NN2)CC RKXXPUWGONIRST-UHFFFAOYSA-N 0.000 claims description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 2
- 201000009267 bronchiectasis Diseases 0.000 claims description 2
- 230000007885 bronchoconstriction Effects 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 208000007451 chronic bronchitis Diseases 0.000 claims description 2
- 201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims description 2
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 238000002651 drug therapy Methods 0.000 claims description 2
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- GEOWCLRLLWTHDN-UHFFFAOYSA-N phenyl formate Chemical compound O=COC1=CC=CC=C1 GEOWCLRLLWTHDN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims 1
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- 201000006938 muscular dystrophy Diseases 0.000 claims 1
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- 239000000203 mixture Substances 0.000 abstract description 34
- 238000011282 treatment Methods 0.000 abstract description 23
- 229910052717 sulfur Inorganic materials 0.000 abstract description 7
- 125000002950 monocyclic group Chemical group 0.000 abstract description 5
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- 125000006163 5-membered heteroaryl group Chemical group 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 179
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 178
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
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- 238000002360 preparation method Methods 0.000 description 126
- 239000000243 solution Substances 0.000 description 113
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 84
- 235000019439 ethyl acetate Nutrition 0.000 description 79
- 238000000746 purification Methods 0.000 description 71
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 56
- 229910052938 sodium sulfate Inorganic materials 0.000 description 55
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
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- 238000004809 thin layer chromatography Methods 0.000 description 33
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- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 14
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2948587C (en) | 2014-05-14 | 2018-07-17 | Pfizer Inc. | Pyrazolopyridines and pyrazolopyrimidines |
| TWI714528B (zh) | 2014-05-14 | 2021-01-01 | 瑞士商諾華公司 | 甲醯胺衍生物 |
| EP3712152B1 (en) | 2015-11-03 | 2021-01-13 | 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 |
| KR20180073687A (ko) * | 2015-11-03 | 2018-07-02 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 호흡기 질환의 치료를 위한 jak 키나제 저해제 화합물 |
| EP3371185B1 (en) | 2015-11-03 | 2020-09-30 | 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 |
| AU2018231035B2 (en) | 2017-03-09 | 2021-09-09 | Theravance Biopharma R&D Ip, Llc | Fused imidazo-piperidine JAK inhibitors |
| JP7096268B2 (ja) | 2017-05-01 | 2022-07-05 | 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阻害剤化合物の結晶形態 |
| EP3609498A1 (en) | 2017-05-01 | 2020-02-19 | Theravance Biopharma R&D IP, LLC | Methods of treatment using 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 |
| TW201920150A (zh) * | 2017-08-01 | 2019-06-01 | 美商施萬生物製藥研發 Ip有限責任公司 | 作為jak激酶抑制劑之吡唑并及三唑并雙環化合物 |
| BR112020008850A2 (pt) | 2017-11-03 | 2020-10-20 | Aclaris Therapeutics, Inc. | composto, composição farmacêutica e método para tratar uma doença mediada por jak1 e jak3 |
| CN119080779A (zh) | 2018-08-10 | 2024-12-06 | 阿克拉瑞斯治疗股份有限公司 | 吡咯并嘧啶itk抑制剂 |
| 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 |
| AU2019335199A1 (en) | 2018-09-04 | 2021-03-11 | Theravance Biopharma R&D Ip, Llc | Process for preparing jak inhibitors and intermediates thereof |
| US10836763B2 (en) | 2018-09-04 | 2020-11-17 | Theravance Biopharma R&D Ip, Llc | 5 to 7 membered heterocyclic amides as JAK inhibitors |
| JP7324836B2 (ja) | 2018-09-04 | 2023-08-10 | 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阻害剤としてのジメチルアミノアゼチジンアミド |
| KR20210084512A (ko) | 2018-10-29 | 2021-07-07 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 억제제로서 2-아자비시클로 헥산 화합물 |
| CN113498352A (zh) | 2019-01-23 | 2021-10-12 | 施万生物制药研发Ip有限责任公司 | 作为jak抑制剂的咪唑并[1,5-a]吡啶、1,2,4-三唑并[4,3-a]吡啶和咪唑并[1,5-a]吡嗪 |
| HUE067145T2 (hu) * | 2019-02-25 | 2024-10-28 | Henan Medinno Pharmaceutical Tech Co Ltd | JAK inhibitor vegyület és alkalmazása |
| 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 |
| 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 |
| AU2020265828A1 (en) | 2019-05-02 | 2021-09-09 | 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 |
| 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 |
| MX2022008627A (es) | 2020-01-13 | 2022-11-08 | Verge Analytics Inc | Pirazolo-pirimidinas sustituidas y usos de las mismas. |
| 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 |
| JP2024524214A (ja) | 2021-06-25 | 2024-07-05 | 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阻害剤としてのイミダゾロインダゾール化合物 |
| 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 |
| IL318992A (en) | 2022-05-02 | 2025-04-01 | Precirix N V | Cancer treatment through advance directives |
| WO2025217560A1 (en) * | 2024-04-12 | 2025-10-16 | Theravance Biopharma R&D Ip, Llc | Triazolo indazole compounds as jak inhibitors |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
| GB9518953D0 (en) | 1995-09-15 | 1995-11-15 | Pfizer Ltd | Pharmaceutical formulations |
| WO2000035298A1 (en) | 1996-11-27 | 2000-06-22 | Wm. Wrigley Jr. Company | Chewing gum containing medicament active agents |
| GB9711643D0 (en) | 1997-06-05 | 1997-07-30 | Janssen Pharmaceutica Nv | Glass thermoplastic systems |
| US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
| EP1562898A1 (en) | 2002-11-19 | 2005-08-17 | Takeda Pharmaceutical Company Limited | 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 |
| JP4782239B2 (ja) | 2007-04-18 | 2011-09-28 | ファイザー・プロダクツ・インク | 異常細胞増殖治療のためのスルホニルアミド誘導体 |
| CN101883774A (zh) * | 2007-10-16 | 2010-11-10 | 惠氏有限责任公司 | 噻吩并嘧啶和吡唑并嘧啶化合物及其用作mtor激酶和pi3激酶抑制剂的用途 |
| JP2011503103A (ja) * | 2007-11-07 | 2011-01-27 | フォールドアールエックス ファーマシューティカルズ インコーポレーティッド | タンパク質輸送の調節方法 |
| US20090149458A1 (en) * | 2007-11-27 | 2009-06-11 | Wyeth | PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS |
| CN102014914A (zh) * | 2008-01-15 | 2011-04-13 | 惠氏有限责任公司 | 3h-[1,2,3]三唑并[4,5-d]嘧啶化合物、其作为mtor激酶和pi3激酶抑制剂的用途、以及它们的合成 |
| JP5608099B2 (ja) * | 2008-01-30 | 2014-10-15 | ジェネンテック， インコーポレイテッド | ピラゾロピリミジンｐｉ３ｋ阻害剤化合物および使用方法 |
| US8163743B2 (en) * | 2008-06-05 | 2012-04-24 | GlaxoGroupLimited | 4-carboxamide indazole derivatives useful as inhibitors of PI3-kinases |
| 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 |
| JPWO2010058846A1 (ja) | 2008-11-21 | 2012-04-19 | 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 |
| US20100317646A1 (en) * | 2009-03-19 | 2010-12-16 | Medical Research Council Technology | Compounds |
| 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 |
| CA2948587C (en) | 2014-05-14 | 2018-07-17 | Pfizer Inc. | Pyrazolopyridines and pyrazolopyrimidines |
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