UA123633C2 - Сполуки інгібітору jak-кінази для лікування респіраторного захворювання - Google Patents
Сполуки інгібітору jak-кінази для лікування респіраторного захворювання Download PDFInfo
- Publication number
- UA123633C2 UA123633C2 UAA201806062A UAA201806062A UA123633C2 UA 123633 C2 UA123633 C2 UA 123633C2 UA A201806062 A UAA201806062 A UA A201806062A UA A201806062 A UAA201806062 A UA A201806062A UA 123633 C2 UA123633 C2 UA 123633C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- compound
- ethyl
- formula
- hydrogen
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 303
- 208000023504 respiratory system disease Diseases 0.000 title claims abstract description 30
- 238000011282 treatment Methods 0.000 title claims abstract description 18
- 229940043355 kinase inhibitor Drugs 0.000 title description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 39
- 238000002360 preparation method Methods 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 88
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 71
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 57
- 239000000725 suspension Substances 0.000 claims description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
- 150000002367 halogens Chemical class 0.000 claims description 39
- -1 substituted Chemical class 0.000 claims description 39
- 208000006673 asthma Diseases 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 239000000843 powder Substances 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 10
- 206010029888 Obliterative bronchiolitis Diseases 0.000 claims description 10
- 206010035664 Pneumonia Diseases 0.000 claims description 10
- 201000003848 bronchiolitis obliterans Diseases 0.000 claims description 10
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims description 10
- 230000003993 interaction Effects 0.000 claims description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000001179 sorption measurement Methods 0.000 claims description 8
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 7
- 206010014561 Emphysema Diseases 0.000 claims description 7
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 7
- 206010035742 Pneumonitis Diseases 0.000 claims description 7
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 7
- 206010069351 acute lung injury Diseases 0.000 claims description 7
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 7
- 206010006451 bronchitis Diseases 0.000 claims description 7
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 7
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 238000003795 desorption Methods 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229940011051 isopropyl acetate Drugs 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 101100231508 Caenorhabditis elegans ceh-5 gene Proteins 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 125000001743 benzylic group Chemical group 0.000 claims 1
- 239000000571 coke Substances 0.000 claims 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 53
- 239000003112 inhibitor Substances 0.000 abstract description 8
- 239000011541 reaction mixture Substances 0.000 description 101
- 239000000203 mixture Substances 0.000 description 68
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 56
- 239000000243 solution Substances 0.000 description 55
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
- 238000004458 analytical method Methods 0.000 description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 39
- 210000004072 lung Anatomy 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 27
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 24
- 238000003556 assay Methods 0.000 description 24
- 230000014759 maintenance of location Effects 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 22
- 238000002953 preparative HPLC Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 17
- 238000002411 thermogravimetry Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 14
- 108090000695 Cytokines Proteins 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- 238000002390 rotary evaporation Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 229940124597 therapeutic agent Drugs 0.000 description 13
- 239000003981 vehicle Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 229940071648 metered dose inhaler Drugs 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000012458 free base Substances 0.000 description 10
- 239000006199 nebulizer Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 210000003979 eosinophil Anatomy 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000013049 sediment Substances 0.000 description 8
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 230000003389 potentiating effect Effects 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000003285 pharmacodynamic effect Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 239000003380 propellant Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 231100000135 cytotoxicity Toxicity 0.000 description 5
- 230000003013 cytotoxicity Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
- VBKNTGMWIPUCRF-UHFFFAOYSA-M potassium;fluoride;hydrofluoride Chemical compound F.[F-].[K+] VBKNTGMWIPUCRF-UHFFFAOYSA-M 0.000 description 5
- 238000000634 powder X-ray diffraction Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 210000002345 respiratory system Anatomy 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 238000005292 vacuum distillation Methods 0.000 description 5
- LTBNCMZYOOIWFC-UHFFFAOYSA-N 1-benzyl-4-iminopyridin-3-amine Chemical compound C1=CC(=N)C(N)=CN1CC1=CC=CC=C1 LTBNCMZYOOIWFC-UHFFFAOYSA-N 0.000 description 4
- GGGMBSBQEAELRI-UHFFFAOYSA-N 2-(2-ethyl-5-fluoro-4-phenylmethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C(C1=CC=CC=C1)OC1=CC(=C(C=C1F)B1OC(C(O1)(C)C)(C)C)CC GGGMBSBQEAELRI-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000029523 Interstitial Lung disease Diseases 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000002327 eosinophilic effect Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 150000005828 hydrofluoroalkanes Chemical class 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000003586 protic polar solvent Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- RKSHRDUFWGVQSL-UHFFFAOYSA-N 1-bromo-2-ethyl-5-fluoro-4-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C(=C1)CC)Br)F RKSHRDUFWGVQSL-UHFFFAOYSA-N 0.000 description 3
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 208000037874 Asthma exacerbation Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 208000000785 Invasive Pulmonary Aspergillosis Diseases 0.000 description 3
- 101100047457 Mus musculus Trpm7 gene Proteins 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001952 enzyme assay Methods 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- JOAKNMHVZBHWFI-UHFFFAOYSA-N 3-methylcyclobutan-1-one Chemical compound CC1CC(=O)C1 JOAKNMHVZBHWFI-UHFFFAOYSA-N 0.000 description 2
- AGPCZZAYJRAENV-UHFFFAOYSA-N 4-bromo-5-ethyl-2-fluorophenol Chemical compound CCC1=CC(O)=C(F)C=C1Br AGPCZZAYJRAENV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 240000005717 Dioscorea alata Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 102100033116 Mitogen-activated protein kinase kinase kinase 20 Human genes 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 2
- 229960004012 amifampridine Drugs 0.000 description 2
- 230000003092 anti-cytokine Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 102000003675 cytokine receptors Human genes 0.000 description 2
- 108010057085 cytokine receptors Proteins 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 229940125369 inhaled corticosteroids Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N methyl tert-butyl ether Substances COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000002733 pharmacodynamic assay Methods 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 208000012802 recumbency Diseases 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- YDBPZCVWPFMBDH-QMMMGPOBSA-N tert-butyl (2s)-2-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C=O YDBPZCVWPFMBDH-QMMMGPOBSA-N 0.000 description 2
- VMKIXWAFFVLJCK-UHFFFAOYSA-N tert-butyl 3-oxoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(=O)C1 VMKIXWAFFVLJCK-UHFFFAOYSA-N 0.000 description 2
- 238000002076 thermal analysis method Methods 0.000 description 2
- 238000001757 thermogravimetry curve Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 108010029307 thymic stromal lymphopoietin Proteins 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- OGFKTAMJLKHRAZ-UHFFFAOYSA-N 2,2-dimethoxyacetaldehyde Chemical compound COC(OC)C=O OGFKTAMJLKHRAZ-UHFFFAOYSA-N 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- FOCKIYZLSZKVDH-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-imidazo[4,5-b]pyridine Chemical group N1C=CC=C2NCNC21 FOCKIYZLSZKVDH-UHFFFAOYSA-N 0.000 description 1
- UKFTXWKNVSVVCJ-UHFFFAOYSA-N 2-[(6-hydrazinylpyridazin-3-yl)-(2-hydroxyethyl)amino]ethanol;hydron;dichloride Chemical class Cl.Cl.NNC1=CC=C(N(CCO)CCO)N=N1 UKFTXWKNVSVVCJ-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- LZKSSLYIICHJEO-UHFFFAOYSA-N 3-methoxycyclobutan-1-one Chemical compound COC1CC(=O)C1 LZKSSLYIICHJEO-UHFFFAOYSA-N 0.000 description 1
- DFPWFKJANMVAIA-UHFFFAOYSA-N 4-bromo-2h-indazole-3-carbaldehyde Chemical compound BrC1=CC=CC2=NNC(C=O)=C12 DFPWFKJANMVAIA-UHFFFAOYSA-N 0.000 description 1
- BKIYTAHLOFDKNE-UHFFFAOYSA-N 4-ethyl-1-fluoro-2-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC(=C1)CC)F BKIYTAHLOFDKNE-UHFFFAOYSA-N 0.000 description 1
- YPTHSYKJDRMAJY-UHFFFAOYSA-N 5-bromo-2-fluorophenol Chemical compound OC1=CC(Br)=CC=C1F YPTHSYKJDRMAJY-UHFFFAOYSA-N 0.000 description 1
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 1
- RQQKGUPOPZJRLE-UHFFFAOYSA-N 6-bromo-2h-indazole-3-carbaldehyde Chemical compound C1=C(Br)C=CC2=C(C=O)NN=C21 RQQKGUPOPZJRLE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000036065 Airway Remodeling Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 241000212977 Andira Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000632511 Daviesia arborea Species 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 101100268058 Dictyostelium discoideum zak2 gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000603223 Homo sapiens Nischarin Proteins 0.000 description 1
- 101000844519 Homo sapiens Transient receptor potential cation channel subfamily M member 6 Proteins 0.000 description 1
- 101000795130 Homo sapiens Trehalase Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101100006982 Mus musculus Ppcdc gene Proteins 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- FUSGACRLAFQQRL-UHFFFAOYSA-N N-Ethyl-N-nitrosourea Chemical compound CCN(N=O)C(N)=O FUSGACRLAFQQRL-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 102100038995 Nischarin Human genes 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 241000801924 Sena Species 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 102000003608 TRPM6 Human genes 0.000 description 1
- 102000015774 TYK2 Kinase Human genes 0.000 description 1
- 108010010057 TYK2 Kinase Proteins 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 239000004012 Tofacitinib Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102100029677 Trehalase Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 238000002083 X-ray spectrum Methods 0.000 description 1
- COERJHDMQUPDCV-UHFFFAOYSA-N [K].FB(F)F Chemical compound [K].FB(F)F COERJHDMQUPDCV-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000013567 aeroallergen Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- MXQOYLRVSVOCQT-UHFFFAOYSA-N bis(tri-t-butylphosphine)palladium (0) Substances [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013000 chemical inhibitor Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000010431 corundum Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229920005994 diacetyl cellulose Polymers 0.000 description 1
- 125000004427 diamine group Chemical group 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- HDVBNSFVCUQRRS-UHFFFAOYSA-N ethane-1,1-diol Chemical compound [CH2]C(O)O HDVBNSFVCUQRRS-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000002129 infrared reflectance spectroscopy Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 231100000016 inhalation toxicity Toxicity 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000004964 innate lymphoid cell Anatomy 0.000 description 1
- 230000035990 intercellular signaling Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229940125389 long-acting beta agonist Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- SURZCVYFPAXNGN-UHFFFAOYSA-N methyl-carbamic acid ethyl ester Chemical compound CCOC(=O)NC SURZCVYFPAXNGN-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002206 pro-fibrotic effect Effects 0.000 description 1
- 230000004647 pro-inflammatory pathway Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 201000009732 pulmonary eosinophilia Diseases 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- ACNRTYKOPZDRCO-UHFFFAOYSA-N tert-butyl n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC=O ACNRTYKOPZDRCO-UHFFFAOYSA-N 0.000 description 1
- BHCQBVYOPYNGKL-UHFFFAOYSA-N tert-butyl n-(3-bromo-2-fluoropropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(F)CBr BHCQBVYOPYNGKL-UHFFFAOYSA-N 0.000 description 1
- MSWTVSDFEYSRMQ-UHFFFAOYSA-N tert-butyl n-methyl-n-(2-oxoethyl)carbamate Chemical compound O=CCN(C)C(=O)OC(C)(C)C MSWTVSDFEYSRMQ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 1
- 229960001350 tofacitinib Drugs 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562250113P | 2015-11-03 | 2015-11-03 | |
| PCT/US2016/059999 WO2017079205A1 (en) | 2015-11-03 | 2016-11-02 | Jak kinase inhibitor compounds for treatment of respiratory disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA123633C2 true UA123633C2 (uk) | 2021-05-05 |
Family
ID=57442794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA201806062A UA123633C2 (uk) | 2015-11-03 | 2016-11-02 | Сполуки інгібітору jak-кінази для лікування респіраторного захворювання |
Country Status (22)
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3712152T3 (da) | 2015-11-03 | 2021-03-22 | Topivert Pharma Ltd | 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridin og 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepinderivater som janus kinase-inhibitorer |
| PL3371185T3 (pl) | 2015-11-03 | 2021-04-06 | Topivert Pharma Limited | Pochodne 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pirydyny i 1,4,5,6,7,8-heksahydroimidazo[4,5-d]azepiny jako inhibitory kinaz janusowych |
| KR20180073687A (ko) | 2015-11-03 | 2018-07-02 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 호흡기 질환의 치료를 위한 jak 키나제 저해제 화합물 |
| JP6974487B2 (ja) | 2017-03-09 | 2021-12-01 | 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 | ４員ヘテロ環式アミドを含むｊａｋ阻害剤 |
| CN110573157B (zh) * | 2017-05-01 | 2023-04-04 | 施万生物制药研发Ip有限责任公司 | 使用jak抑制剂化合物的治疗方法 |
| AU2018261591B2 (en) | 2017-05-01 | 2021-09-02 | 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 |
| WO2019104225A1 (en) | 2017-11-22 | 2019-05-31 | Dauntless 2, Inc. | Therapeutic compound formulations |
| EP3810094A1 (en) | 2018-06-20 | 2021-04-28 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a jak or other kinase inhibitor |
| SG11202101785UA (en) * | 2018-09-04 | 2021-03-30 | Theravance Biopharma R&D Ip Llc | Process for preparing jak inhibitors and intermediates thereof |
| FI3837258T3 (fi) | 2018-09-04 | 2024-05-27 | Theravance Biopharma R&D Ip Llc | Dimetyyliaminoatsetidiiniamideja jak-estäjinä |
| KR20210056380A (ko) | 2018-09-04 | 2021-05-18 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 억제제로서 5원 내지 7원 헤테로사이클릭 아마이드 |
| MX2021004582A (es) * | 2018-10-29 | 2021-06-15 | Theravance Biopharma R&D Ip Llc | Compuesto 2-azabiciclo hexano inhibidor de jak. |
| CN113316577A (zh) | 2018-11-19 | 2021-08-27 | 纽约大学 | 作为治疗剂的GLi1抑制剂 |
| JP7514025B2 (ja) * | 2019-02-25 | 2024-07-10 | ホーナン メディノ ファーマシューティカル テクノロジー カンパニー リミテッド | Ｊａｋ阻害剤化合物及びその使用 |
| 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 |
| KR20210137087A (ko) | 2019-03-05 | 2021-11-17 | 인사이트 코포레이션 | 만성 폐 동종이식 기능장애의 치료를 위한 jak1 경로 억제제 |
| BR112021018168B1 (pt) | 2019-03-21 | 2023-11-28 | Onxeo | Composição farmacêutica, combinação e kit compreendendo uma molécula dbait e um inibidor de quinase para o tratamento de câncer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021136345A1 (zh) * | 2019-12-30 | 2021-07-08 | 路良 | Jak抑制剂化合物及其用途 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| 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 |
| WO2022178215A1 (en) | 2021-02-19 | 2022-08-25 | Theravance Biopharma R&D Ip, Llc | Amino amide tetrahydro imidazo pyridines as jak inhibitors |
| CN117083273A (zh) | 2021-03-26 | 2023-11-17 | 施万生物制药研发Ip有限责任公司 | Jak抑制剂化合物的二盐酸盐的晶型 |
| 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 |
| CN114181055A (zh) * | 2021-12-21 | 2022-03-15 | 苏州楚凯药业有限公司 | 1-苄氧基-4-溴-5-乙基-2-氟苯的制备方法 |
| JP2025515078A (ja) | 2022-05-05 | 2025-05-13 | 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 | 噴霧経口吸入による送達のためのネズルシチニブ |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| CA2532800C (en) | 2003-07-23 | 2013-06-18 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
| US20050090529A1 (en) | 2003-07-31 | 2005-04-28 | Pfizer Inc | 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
| US7884109B2 (en) | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
| DK2089369T3 (da) | 2006-10-19 | 2011-05-09 | Rigel Pharmaceuticals Inc | 2,4-pyrimidindiaminderivater som hæmmere af JAK-kinaser til behandling af autoimmune sygdomme |
| US8648069B2 (en) | 2007-06-08 | 2014-02-11 | Abbvie Inc. | 5-substituted indazoles as kinase inhibitors |
| JP5512665B2 (ja) | 2008-06-20 | 2014-06-04 | ジェネンテック， インコーポレイテッド | トリアゾロピリジンｊａｋ阻害剤化合物と方法 |
| US20110184013A1 (en) | 2008-10-01 | 2011-07-28 | Shelley Allen | Imidazo[1,2-a]Pyridine Compounds As Receptor Tyrosine Kinase Inhibitors |
| CL2009001884A1 (es) * | 2008-10-02 | 2010-05-14 | Incyte Holdings Corp | Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco. |
| JP2010111624A (ja) | 2008-11-06 | 2010-05-20 | Shionogi & Co Ltd | Ｔｔｋ阻害作用を有するインダゾール誘導体 |
| JP5651681B2 (ja) | 2009-04-03 | 2015-01-14 | 大日本住友製薬株式会社 | 代謝型グルタミン酸受容体５介在障害の治療のための化合物、およびその使用方法 |
| EP2459195A1 (en) | 2009-07-28 | 2012-06-06 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| ES2652287T3 (es) | 2009-12-21 | 2018-02-01 | Samumed, Llc | 1H-pirazol [3,4-b] piridinas y usos terapéuticos de las mismas |
| EP2338888A1 (en) | 2009-12-24 | 2011-06-29 | Almirall, S.A. | Imidazopyridine derivatives as JAK inhibitors |
| CN103476770B (zh) | 2010-11-25 | 2017-02-15 | 拉蒂欧制药有限责任公司 | 阿法替尼盐和多晶型物 |
| US8575336B2 (en) | 2011-07-27 | 2013-11-05 | Pfizer Limited | Indazoles |
| PH12017500997A1 (en) | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
| TW201513861A (zh) * | 2013-01-17 | 2015-04-16 | Galapagos Nv | 用於治療退化性及發炎疾病之新穎化合物 |
| MD4649C1 (ro) | 2013-12-05 | 2020-04-30 | Pfizer Inc. | Pirol[2,3-d]pirimidinil, pirol[2,3-b]pirazinil şi pirol[2,3-d]piridinil acrilamide |
| ES2737696T3 (es) * | 2014-05-14 | 2020-01-15 | Pfizer | Pirazolopiridinas y pirazolopirimidinas |
| WO2016026078A1 (en) | 2014-08-19 | 2016-02-25 | Changzhou Jiekai Pharmatech Co., Ltd. | Heterocyclic compounds as erk inhibitors |
| KR101663277B1 (ko) | 2015-03-30 | 2016-10-06 | 주식회사 녹십자 | TNIK, IKKε 및 TBK1 억제제로서의 피라졸계 유도체 및 이를 포함하는 약학적 조성물 |
| DK3712152T3 (da) | 2015-11-03 | 2021-03-22 | Topivert Pharma Ltd | 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridin og 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepinderivater som janus kinase-inhibitorer |
| PL3371185T3 (pl) | 2015-11-03 | 2021-04-06 | Topivert Pharma Limited | Pochodne 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pirydyny i 1,4,5,6,7,8-heksahydroimidazo[4,5-d]azepiny jako inhibitory kinaz janusowych |
| KR20180073687A (ko) | 2015-11-03 | 2018-07-02 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 호흡기 질환의 치료를 위한 jak 키나제 저해제 화합물 |
| JP6974487B2 (ja) | 2017-03-09 | 2021-12-01 | 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 | ４員ヘテロ環式アミドを含むｊａｋ阻害剤 |
| CN110573157B (zh) | 2017-05-01 | 2023-04-04 | 施万生物制药研发Ip有限责任公司 | 使用jak抑制剂化合物的治疗方法 |
| AR111495A1 (es) | 2017-05-01 | 2019-07-17 | Theravance Biopharma R&D Ip Llc | Compuestos de imidazo-piperidina fusionada como inhibidores de jak |
| AU2018261591B2 (en) | 2017-05-01 | 2021-09-02 | Theravance Biopharma R&D Ip, Llc | Crystalline forms of a JAK inhibitor compound |
| SG11202101785UA (en) | 2018-09-04 | 2021-03-30 | Theravance Biopharma R&D Ip Llc | Process for preparing jak inhibitors and intermediates thereof |
| FI3837258T3 (fi) | 2018-09-04 | 2024-05-27 | Theravance Biopharma R&D Ip Llc | Dimetyyliaminoatsetidiiniamideja jak-estäjinä |
| KR20210056380A (ko) | 2018-09-04 | 2021-05-18 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | Jak 억제제로서 5원 내지 7원 헤테로사이클릭 아마이드 |
| MX2021004582A (es) | 2018-10-29 | 2021-06-15 | Theravance Biopharma R&D Ip Llc | Compuesto 2-azabiciclo hexano inhibidor de jak. |
| CN117083273A (zh) | 2021-03-26 | 2023-11-17 | 施万生物制药研发Ip有限责任公司 | Jak抑制剂化合物的二盐酸盐的晶型 |
-
2016
- 2016-11-02 KR KR1020187015680A patent/KR20180073687A/ko not_active Withdrawn
- 2016-11-02 TW TW105135436A patent/TWI710560B/zh not_active IP Right Cessation
- 2016-11-02 MY MYPI2018701385A patent/MY195427A/en unknown
- 2016-11-02 HK HK18111992.5A patent/HK1252685A1/zh unknown
- 2016-11-02 EP EP16804947.6A patent/EP3371186A1/en not_active Withdrawn
- 2016-11-02 AU AU2016350816A patent/AU2016350816B2/en not_active Ceased
- 2016-11-02 WO PCT/US2016/059999 patent/WO2017079205A1/en not_active Ceased
- 2016-11-02 CA CA3001542A patent/CA3001542C/en active Active
- 2016-11-02 MX MX2018005446A patent/MX374605B/es active IP Right Grant
- 2016-11-02 CN CN201680063886.1A patent/CN108349972B/zh not_active Expired - Fee Related
- 2016-11-02 BR BR112018008966-4A patent/BR112018008966B1/pt not_active IP Right Cessation
- 2016-11-02 UA UAA201806062A patent/UA123633C2/uk unknown
- 2016-11-02 US US15/341,226 patent/US10100049B2/en active Active
- 2016-11-02 JP JP2018522556A patent/JP6800969B2/ja not_active Expired - Fee Related
- 2016-11-02 EA EA201891091A patent/EA034914B1/ru unknown
- 2016-11-02 NZ NZ741737A patent/NZ741737A/en unknown
- 2016-11-02 PH PH1/2018/500828A patent/PH12018500828B1/en unknown
-
2018
- 2018-04-16 ZA ZA2018/02496A patent/ZA201802496B/en unknown
- 2018-04-17 IL IL258772A patent/IL258772B/en active IP Right Grant
- 2018-04-30 CL CL2018001145A patent/CL2018001145A1/es unknown
- 2018-04-30 SA SA518391470A patent/SA518391470B1/ar unknown
- 2018-05-29 CO CONC2018/0005640A patent/CO2018005640A2/es unknown
- 2018-07-18 US US16/038,424 patent/US10183942B2/en active Active
- 2018-12-10 US US16/215,194 patent/US10526330B2/en active Active
-
2019
- 2019-11-20 US US16/689,706 patent/US10913740B2/en not_active Expired - Fee Related
-
2021
- 2021-01-05 US US17/248,015 patent/US11299492B2/en active Active
-
2022
- 2022-03-07 US US17/688,001 patent/US11718616B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA123633C2 (uk) | Сполуки інгібітору jak-кінази для лікування респіраторного захворювання | |
| EP3464245B1 (en) | Benzazepine dicarboxamide compounds with tertiary amide function | |
| KR102244257B1 (ko) | Jak 키나제 저해제로서 피리미딘 화합물 | |
| EP3921320B1 (en) | Imidazo [2, 1-f] [1, 2, 4] triazin-4-amine derivatives as tlr7 agonist | |
| US20230357277A1 (en) | Kras g12d inhibitors | |
| US10562891B2 (en) | Quinazolinones as PARP14 inhibitors | |
| EP3266785A1 (en) | Toll-like receptor-7 agonist | |
| KR20170023156A (ko) | 단백질 키나제 저해제로서의 아미노피리다지논 화합물 | |
| EP2170886A1 (en) | 9h-pyrimido[4,5-b]indoles, 9h-pyrido[4',3':4,5]pyrrolo[2,3-d]pyridines, and 9h-1,3,6,9-tetraaza-fluorenes as chk1 kinase function inhibitors | |
| UA127328C2 (uk) | 5-7-членні гетероциклічні аміди як інгібітори jak | |
| AU2021238799A1 (en) | Fused bicyclic derivative, preparation method therefor, and pharmaceutical use thereof | |
| EP4180434A1 (en) | Pb2 inhibitor, and preparation method therefor and use thereof | |
| TW202448857A (zh) | 含有芳香二並環的化合物 | |
| HK40002463A (en) | Benzazepine dicarboxamide compounds with tertiary amide function |