KR101944914B1 - 치환된 피리미딘 화합물 및 syk 억제제로서의 이의 용도 - Google Patents
치환된 피리미딘 화합물 및 syk 억제제로서의 이의 용도 Download PDFInfo
- Publication number
- KR101944914B1 KR101944914B1 KR1020147023266A KR20147023266A KR101944914B1 KR 101944914 B1 KR101944914 B1 KR 101944914B1 KR 1020147023266 A KR1020147023266 A KR 1020147023266A KR 20147023266 A KR20147023266 A KR 20147023266A KR 101944914 B1 KR101944914 B1 KR 101944914B1
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- pyrimidin
- ylamino
- indol
- pyrazol
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 15
- 150000003230 pyrimidines Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 294
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 80
- 201000010099 disease Diseases 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 54
- -1 amino, hydroxy Chemical group 0.000 claims description 302
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 196
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims description 59
- 125000005843 halogen group Chemical group 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 229920006395 saturated elastomer Polymers 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000002950 monocyclic group Chemical group 0.000 claims description 39
- 125000005842 heteroatom Chemical group 0.000 claims description 32
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 29
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 208000006673 asthma Diseases 0.000 claims description 16
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000001301 oxygen Chemical group 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 239000011593 sulfur Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 150000003457 sulfones Chemical group 0.000 claims description 10
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000003462 sulfoxides Chemical group 0.000 claims description 9
- 206010025323 Lymphomas Diseases 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 5
- JSFJBYKBNANORA-OAQYLSRUSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypiperidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CCC[C@@H](O)C1 JSFJBYKBNANORA-OAQYLSRUSA-N 0.000 claims description 4
- FNGJTJGYKVSXHA-HXUWFJFHSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 FNGJTJGYKVSXHA-HXUWFJFHSA-N 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- FLGSFJVMDOPSIH-GOSISDBHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound C1=C2C(C(=O)C)=CNC2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC[C@@H](O)C1 FLGSFJVMDOPSIH-GOSISDBHSA-N 0.000 claims description 3
- PQBYPDZGIKKGIO-MRXNPFEDSA-N 2,2,2-trifluoro-1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]ethanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(F)(F)F)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 PQBYPDZGIKKGIO-MRXNPFEDSA-N 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims description 2
- GYPNQERNJVTKMG-HXUWFJFHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2,2-dimethylpropan-1-one Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C(C)(C)C)=CN(C)C4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 GYPNQERNJVTKMG-HXUWFJFHSA-N 0.000 claims description 2
- ZTMHYNAQJHVBSB-HXUWFJFHSA-N 1-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]-2-methylpropan-1-one Chemical compound C1=C2C(C(=O)C(C)C)=CN(C)C2=CC=C1NC(N=1)=NC=CC=1N(N=C1C)C=C1CN1CC[C@@H](O)C1 ZTMHYNAQJHVBSB-HXUWFJFHSA-N 0.000 claims description 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- WTXAPTXRAFQESK-UHFFFAOYSA-N CN1C(N=CC=C1CN1CC(C(C1)O)O)NC=1C=C2C(=CN(C2=CC=1)C)S(=O)(=O)C Chemical compound CN1C(N=CC=C1CN1CC(C(C1)O)O)NC=1C=C2C(=CN(C2=CC=1)C)S(=O)(=O)C WTXAPTXRAFQESK-UHFFFAOYSA-N 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 102000000551 Syk Kinase Human genes 0.000 abstract description 69
- 108010016672 Syk Kinase Proteins 0.000 abstract description 69
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 28
- 102000020233 phosphotransferase Human genes 0.000 abstract description 28
- 208000035475 disorder Diseases 0.000 abstract description 25
- 230000002401 inhibitory effect Effects 0.000 abstract description 18
- 230000001404 mediated effect Effects 0.000 abstract description 18
- 125000003118 aryl group Chemical group 0.000 description 70
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 206010057190 Respiratory tract infections Diseases 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 239000000543 intermediate Substances 0.000 description 32
- 239000000243 solution Substances 0.000 description 30
- 239000007787 solid Substances 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- 239000002585 base Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 206010028980 Neoplasm Diseases 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 238000004809 thin layer chromatography Methods 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- KCZIRQGMWBGPRP-UHFFFAOYSA-N 2-(2-hydroxyacetyl)oxyethyl 2-hydroxyacetate Chemical compound OCC(=O)OCCOC(=O)CO KCZIRQGMWBGPRP-UHFFFAOYSA-N 0.000 description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 12
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 125000003710 aryl alkyl group Chemical group 0.000 description 11
- 210000003719 b-lymphocyte Anatomy 0.000 description 11
- JCZPOYAMKJFOLA-ZXZARUISSA-N (3s,4r)-pyrrolidine-3,4-diol Chemical compound O[C@H]1CNC[C@H]1O JCZPOYAMKJFOLA-ZXZARUISSA-N 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 102000001253 Protein Kinase Human genes 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 206010003246 arthritis Diseases 0.000 description 9
- 108060006633 protein kinase Proteins 0.000 description 9
- 208000024172 Cardiovascular disease Diseases 0.000 description 8
- 208000009386 Experimental Arthritis Diseases 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- UIOROHDPLCUDRI-UHFFFAOYSA-N 1-[[2-[(3-chloro-1-cyclopropylindol-5-yl)amino]pyrimidin-4-yl]methyl]pyrrolidin-3-ol Chemical compound ClC1=CN(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(CC1)O)C1CC1 UIOROHDPLCUDRI-UHFFFAOYSA-N 0.000 description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 7
- 208000023275 Autoimmune disease Diseases 0.000 description 7
- 150000001204 N-oxides Chemical class 0.000 description 7
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 7
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 7
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 238000012544 monitoring process Methods 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 230000019491 signal transduction Effects 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- 201000004624 Dermatitis Diseases 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 208000001132 Osteoporosis Diseases 0.000 description 5
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 201000010105 allergic rhinitis Diseases 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 210000003630 histaminocyte Anatomy 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 5
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 5
- 229960001860 salicylate Drugs 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000029725 Metabolic bone disease Diseases 0.000 description 4
- 206010049088 Osteopenia Diseases 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 208000024780 Urticaria Diseases 0.000 description 4
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 239000013566 allergen Substances 0.000 description 4
- 150000001448 anilines Chemical class 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000002393 azetidinyl group Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 208000023504 respiratory system disease Diseases 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- BXOQVJJXDGBKPI-UHFFFAOYSA-N 1-[[2-[(3-bromo-1,2-dimethylindol-5-yl)amino]pyrimidin-4-yl]methyl]pyrrolidin-3-ol Chemical compound BrC1=C(N(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(CC1)O)C)C BXOQVJJXDGBKPI-UHFFFAOYSA-N 0.000 description 3
- QVSDFQQPORLXJH-UHFFFAOYSA-N 1-[[2-[(3-chloro-1-methylindol-5-yl)amino]pyrimidin-4-yl]methyl]piperidin-3-ol Chemical compound ClC1=CN(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(CCC1)O)C QVSDFQQPORLXJH-UHFFFAOYSA-N 0.000 description 3
- LZYUJHWKCOTVHA-UHFFFAOYSA-N 1-[[2-[(3-chloro-1-methylindol-5-yl)amino]pyrimidin-4-yl]methyl]pyrrolidin-3-ol Chemical compound ClC1=CN(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(CC1)O)C LZYUJHWKCOTVHA-UHFFFAOYSA-N 0.000 description 3
- IQPSHDIJCGVRRY-UHFFFAOYSA-N 1-[[2-[(3-chloro-1-propan-2-ylindazol-5-yl)amino]-5-fluoro-2H-pyrimidin-1-yl]methyl]azetidin-3-ol Chemical compound ClC1=NN(C2=CC=C(C=C12)NC1N=CC(=CN1CN1CC(C1)O)F)C(C)C IQPSHDIJCGVRRY-UHFFFAOYSA-N 0.000 description 3
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 102000000503 Collagen Type II Human genes 0.000 description 3
- 108010041390 Collagen Type II Proteins 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- BQLHQKYDCMONAY-UHFFFAOYSA-N N-(1-hydroxy-2H-pyrimidin-2-yl)-1-methylindazol-5-amine Chemical compound CN1N=CC2=CC(=CC=C12)NC1N=CC=CN1O BQLHQKYDCMONAY-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 206010039085 Rhinitis allergic Diseases 0.000 description 3
- 206010039710 Scleroderma Diseases 0.000 description 3
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 3
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 3
- 244000269722 Thea sinensis Species 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 230000002917 arthritic effect Effects 0.000 description 3
- UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 3
- 229940077388 benzenesulfonate Drugs 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 208000024376 chronic urticaria Diseases 0.000 description 3
- 239000004927 clay Substances 0.000 description 3
- 238000007872 degassing Methods 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- HHYVTIKYZUMDIL-UHFFFAOYSA-N ethyl 5-methyl-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1C HHYVTIKYZUMDIL-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 206010039083 rhinitis Diseases 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical group FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 3
- 102000003390 tumor necrosis factor Human genes 0.000 description 3
- 210000000707 wrist Anatomy 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- AEXUKUURUILLIM-UHFFFAOYSA-N 1-[[2-[(3-bromo-1,2-dimethylindol-5-yl)amino]pyrimidin-4-yl]methyl]pyrrolidine-3,4-diol Chemical compound BrC1=C(N(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(C(C1)O)O)C)C AEXUKUURUILLIM-UHFFFAOYSA-N 0.000 description 2
- VGEAACJRPVSNBW-UHFFFAOYSA-N 1-[[2-[(3-chloro-2-methyl-1-propylindol-5-yl)amino]pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound ClC1=C(N(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(C1)O)CCC)C VGEAACJRPVSNBW-UHFFFAOYSA-N 0.000 description 2
- CARQEPZVMJFAMO-UHFFFAOYSA-N 1-[[2-[(3-chloro-2-methyl-1-propylindol-5-yl)amino]pyrimidin-4-yl]methyl]pyrrolidine-3,4-diol Chemical compound ClC1=C(N(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(C(C1)O)O)CCC)C CARQEPZVMJFAMO-UHFFFAOYSA-N 0.000 description 2
- UDXZSKYFENDKBK-UHFFFAOYSA-N 1-[[3-methyl-2-[(1-methyl-3-methylsulfonylindazol-5-yl)amino]-2H-pyrimidin-4-yl]methyl]pyrrolidine-3,4-diol Chemical compound CN1C(N=CC=C1CN1CC(C(C1)O)O)NC=1C=C2C(=NN(C2=CC=1)C)S(=O)(=O)C UDXZSKYFENDKBK-UHFFFAOYSA-N 0.000 description 2
- YVNBTRJHFISUOU-UHFFFAOYSA-N 1-methyl-n-(4-methylsulfonylpyrimidin-2-yl)indazol-5-amine Chemical compound C=1C=C2N(C)N=CC2=CC=1NC1=NC=CC(S(C)(=O)=O)=N1 YVNBTRJHFISUOU-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 2
- VAATWVRXPRDPPM-UHFFFAOYSA-N 2-chloro-4-methylsulfanylpyrimidine Chemical compound CSC1=CC=NC(Cl)=N1 VAATWVRXPRDPPM-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 2
- UOANXMOBZOZVSF-UHFFFAOYSA-N 3-cyclopentyl-1-methyl-N-pyrimidin-2-ylindol-5-amine Chemical compound C1(CCCC1)C1=CN(C2=CC=C(C=C12)NC1=NC=CC=N1)C UOANXMOBZOZVSF-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N 3-methoxypyridine Chemical compound COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010002329 Aneurysm Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 206010007513 Cardiac aneurysm Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000027932 Collagen disease Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 208000004196 Heart Aneurysm Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 101000604583 Homo sapiens Tyrosine-protein kinase SYK Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000011200 Kawasaki disease Diseases 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- 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 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- KBNFBWIJBQLUTL-UHFFFAOYSA-N N-(1-hydroxy-2H-pyrimidin-2-yl)-1-methylsulfonyl-2,3-dihydroindol-5-amine Chemical compound CS(=O)(=O)N1CCC2=CC(=CC=C12)NC1N=CC=CN1O KBNFBWIJBQLUTL-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000036284 Rhinitis seasonal Diseases 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000032450 Surgical Shock Diseases 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 206010044541 Traumatic shock Diseases 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010052568 Urticaria chronic Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- LXRROUCWANUVLT-UHFFFAOYSA-J [C+4].[O-]C(=O)CCC([O-])=O.[O-]C(=O)CCC([O-])=O Chemical compound [C+4].[O-]C(=O)CCC([O-])=O.[O-]C(=O)CCC([O-])=O LXRROUCWANUVLT-UHFFFAOYSA-J 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 210000003423 ankle Anatomy 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- JYYPBMCCVZPTIB-UHFFFAOYSA-N azetidin-3-ol pyrimidine Chemical compound N1=CN=CC=C1.OC1CNC1 JYYPBMCCVZPTIB-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 2
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 2
- MYJQGGALXPHWLV-UHFFFAOYSA-N cyclopentane-1,2-diamine Chemical compound NC1CCCC1N MYJQGGALXPHWLV-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 238000011143 downstream manufacturing Methods 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- GYABPRBXLRWZMM-UHFFFAOYSA-N ethyl 1-(2-chloropyrimidin-4-yl)-3-methylpyrazole-4-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CN1C1=CC=NC(Cl)=N1 GYABPRBXLRWZMM-UHFFFAOYSA-N 0.000 description 2
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 102000045613 human SYK Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 208000005368 osteomalacia Diseases 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 229940014662 pantothenate Drugs 0.000 description 2
- 235000019161 pantothenic acid Nutrition 0.000 description 2
- 239000011713 pantothenic acid Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000009325 pulmonary function Effects 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 208000017022 seasonal allergic rhinitis Diseases 0.000 description 2
- 206010040560 shock Diseases 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 2
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- NLVZYRDCKUFONR-CRCLSJGQSA-N (3s,4r)-4-methoxypyrrolidin-3-ol Chemical compound CO[C@@H]1CNC[C@@H]1O NLVZYRDCKUFONR-CRCLSJGQSA-N 0.000 description 1
- HZNFYZVGMQAREI-UHFFFAOYSA-N (4-acetyloxypyrrolidin-3-yl) acetate Chemical compound CC(=O)OC1CNCC1OC(C)=O HZNFYZVGMQAREI-UHFFFAOYSA-N 0.000 description 1
- 0 *C(IC1)I#I1=C Chemical compound *C(IC1)I#I1=C 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- 150000005056 1,6-naphthyridines Chemical class 0.000 description 1
- OMOCVUPRTIPABZ-UHFFFAOYSA-N 1-(1h-imidazol-2-yl)piperidine Chemical compound C1CCCCN1C1=NC=CN1 OMOCVUPRTIPABZ-UHFFFAOYSA-N 0.000 description 1
- NGEXODJJSQPXEC-UHFFFAOYSA-N 1-(2-chloropyrimidin-4-yl)-3-methylpyrazole-4-carbaldehyde Chemical compound C1=C(C=O)C(C)=NN1C1=CC=NC(Cl)=N1 NGEXODJJSQPXEC-UHFFFAOYSA-N 0.000 description 1
- VCMVIZREDYIHDQ-UHFFFAOYSA-N 1-(2-methoxyethyl)-N-pyrimidin-2-ylindol-5-amine Chemical compound COCCN1C=CC2=CC(=CC=C12)NC1=NC=CC=N1 VCMVIZREDYIHDQ-UHFFFAOYSA-N 0.000 description 1
- UPOKONTULAALTC-UHFFFAOYSA-N 1-[[2-[(2,3-dimethyl-1-propan-2-ylindol-5-yl)amino]pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound C(C)(C)N1C(=C(C2=CC(=CC=C12)NC1=NC=CC(=N1)CN1CC(C1)O)C)C UPOKONTULAALTC-UHFFFAOYSA-N 0.000 description 1
- LNEUZIABQBZBRT-UHFFFAOYSA-N 1-[[2-[(3-chloro-1,2-dimethylindol-5-yl)amino]-5-fluoropyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound ClC1=C(N(C2=CC=C(C=C12)NC1=NC=C(C(=N1)CN1CC(C1)O)F)C)C LNEUZIABQBZBRT-UHFFFAOYSA-N 0.000 description 1
- ZSQADRIFDPUMQC-UHFFFAOYSA-N 1-[[2-[(3-chloro-1-methylindol-5-yl)amino]pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound ClC1=CN(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(C1)O)C ZSQADRIFDPUMQC-UHFFFAOYSA-N 0.000 description 1
- RJRVGKZNPKLYFA-UHFFFAOYSA-N 1-[[2-[[3-(furan-3-yl)-1-methylindol-5-yl]amino]pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound O1C=C(C=C1)C1=CN(C2=CC=C(C=C12)NC1=NC=CC(=N1)CN1CC(C1)O)C RJRVGKZNPKLYFA-UHFFFAOYSA-N 0.000 description 1
- NJQWPSHILRYPGX-UHFFFAOYSA-N 1-[[2-[[3-(morpholin-4-ylmethyl)-1-propan-2-ylindol-5-yl]amino]pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound C(C)(C)N1C=C(C2=CC(=CC=C12)NC1=NC=CC(=N1)CN1CC(C1)O)CN1CCOCC1 NJQWPSHILRYPGX-UHFFFAOYSA-N 0.000 description 1
- BVMPWTYAUMFDRZ-UHFFFAOYSA-N 1-[[3-methyl-2-[(1-methyl-3-morpholin-4-ylindazol-5-yl)amino]-2H-pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound CN1C(N=CC=C1CN1CC(C1)O)NC=1C=C2C(=NN(C2=CC=1)C)N1CCOCC1 BVMPWTYAUMFDRZ-UHFFFAOYSA-N 0.000 description 1
- KZWMNXSWZKWHKT-UHFFFAOYSA-N 1-[[3-methyl-2-[(1-methylindazol-5-yl)amino]-2H-pyrimidin-4-yl]methyl]pyrrolidine-3,4-diol Chemical compound CN1C(N=CC=C1CN1CC(C(C1)O)O)NC=1C=C2C=NN(C2=CC=1)C KZWMNXSWZKWHKT-UHFFFAOYSA-N 0.000 description 1
- AZUAKPGPHHECSS-UHFFFAOYSA-N 1-[[3-methyl-2-[(1-methylindazol-5-yl)amino]-5-(trifluoromethyl)-2H-pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound CN1C(N=CC(=C1CN1CC(C1)O)C(F)(F)F)NC=1C=C2C=NN(C2=CC=1)C AZUAKPGPHHECSS-UHFFFAOYSA-N 0.000 description 1
- VFCKNWNOHPFPQK-UHFFFAOYSA-N 1-[[3-methyl-2-[[1-methyl-3-(1,3-oxazol-5-yl)indol-5-yl]amino]-2H-pyrimidin-4-yl]methyl]azetidin-3-ol Chemical compound CN1C(N=CC=C1CN1CC(C1)O)NC=1C=C2C(=CN(C2=CC=1)C)C1=CN=CO1 VFCKNWNOHPFPQK-UHFFFAOYSA-N 0.000 description 1
- CPQPCQRZRUPGKG-UHFFFAOYSA-N 1-cyclobutyl-N-(1-hydroxy-2H-pyrimidin-2-yl)indol-5-amine Chemical compound C1(CCC1)N1C=CC2=CC(=CC=C12)NC1N=CC=CN1O CPQPCQRZRUPGKG-UHFFFAOYSA-N 0.000 description 1
- YTCVLSIGCNQYIO-UHFFFAOYSA-N 1-cyclopropyl-N-(1-hydroxy-2H-pyrimidin-2-yl)indazol-5-amine Chemical compound C1(CC1)N1N=CC2=CC(=CC=C12)NC1N=CC=CN1O YTCVLSIGCNQYIO-UHFFFAOYSA-N 0.000 description 1
- KHIVHAYYUUFWPH-UHFFFAOYSA-N 1-ethyl-3-methylpyrazole-4-carbaldehyde Chemical compound CCN1C=C(C=O)C(C)=N1 KHIVHAYYUUFWPH-UHFFFAOYSA-N 0.000 description 1
- IIUZGXWMYOKTGR-UHFFFAOYSA-N 1-ethyl-N-(1-hydroxy-2H-pyrimidin-2-yl)indol-5-amine Chemical compound C(C)N1C=CC2=CC(=CC=C12)NC1N=CC=CN1O IIUZGXWMYOKTGR-UHFFFAOYSA-N 0.000 description 1
- IFLSQMKJKMIYDM-UHFFFAOYSA-N 1-methyl-3-morpholin-4-yl-N-pyrimidin-2-ylindazol-5-amine Chemical compound CN1N=C(C2=CC(=CC=C12)NC1=NC=CC=N1)N1CCOCC1 IFLSQMKJKMIYDM-UHFFFAOYSA-N 0.000 description 1
- VRUACLINTHAQSL-UHFFFAOYSA-N 1-methyl-N-pyrimidin-2-yl-2,3-dihydroindol-5-amine Chemical compound CN1CCC2=CC(=CC=C12)NC1=NC=CC=N1 VRUACLINTHAQSL-UHFFFAOYSA-N 0.000 description 1
- RQJDJIAZPAJRIK-UHFFFAOYSA-N 1-methyl-n-(4-methylsulfanylpyrimidin-2-yl)indazol-5-amine Chemical compound CSC1=CC=NC(NC=2C=C3C=NN(C)C3=CC=2)=N1 RQJDJIAZPAJRIK-UHFFFAOYSA-N 0.000 description 1
- PYOFNPHTKBSXOM-UHFFFAOYSA-N 1-methylindazol-5-amine Chemical compound NC1=CC=C2N(C)N=CC2=C1 PYOFNPHTKBSXOM-UHFFFAOYSA-N 0.000 description 1
- CSUGQXMRKOKBFI-UHFFFAOYSA-N 1-methylindazole Chemical compound C1=CC=C2N(C)N=CC2=C1 CSUGQXMRKOKBFI-UHFFFAOYSA-N 0.000 description 1
- MAHAMBLNIDMREX-UHFFFAOYSA-N 1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1 MAHAMBLNIDMREX-UHFFFAOYSA-N 0.000 description 1
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
- FEDVXUAIKUFBBM-UHFFFAOYSA-N 2,3-dimethyl-1-propan-2-yl-N-pyrimidin-2-ylindol-5-amine Chemical compound C(C)(C)N1C(=C(C2=CC(=CC=C12)NC1=NC=CC=N1)C)C FEDVXUAIKUFBBM-UHFFFAOYSA-N 0.000 description 1
- YFYFVWTWMBQHOH-UHFFFAOYSA-N 2,4-dichloro-5-ethylpyrimidine Chemical compound CCC1=CN=C(Cl)N=C1Cl YFYFVWTWMBQHOH-UHFFFAOYSA-N 0.000 description 1
- TVFRRCHBPNUHBY-UHFFFAOYSA-N 2-[(1-methylindazol-5-yl)amino]-2H-pyrimidine-1-carboxylic acid Chemical compound CN1N=CC2=CC(=CC=C12)NC1N=CC=CN1C(=O)O TVFRRCHBPNUHBY-UHFFFAOYSA-N 0.000 description 1
- HCRCYHSUIHDLJG-UHFFFAOYSA-N 2-[5-(pyrimidin-2-ylamino)indol-1-yl]ethanol Chemical compound OCCN1C=CC2=CC(=CC=C12)NC1=NC=CC=N1 HCRCYHSUIHDLJG-UHFFFAOYSA-N 0.000 description 1
- AGYUQBNABXVWMS-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1 AGYUQBNABXVWMS-UHFFFAOYSA-N 0.000 description 1
- IUKSYUOJRHDWRR-UHFFFAOYSA-N 2-diazonio-4,6-dinitrophenolate Chemical compound [O-]C1=C([N+]#N)C=C([N+]([O-])=O)C=C1[N+]([O-])=O IUKSYUOJRHDWRR-UHFFFAOYSA-N 0.000 description 1
- RHILFGWTFQDWBC-UHFFFAOYSA-N 3,4-dihydroxypyrrolidin-2-one Chemical compound OC1CNC(=O)C1O RHILFGWTFQDWBC-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XBMURFMYQSJQEW-UHFFFAOYSA-N 3-bromo-1,2-dimethyl-N-pyrimidin-2-ylindol-5-amine Chemical compound BrC1=C(N(C2=CC=C(C=C12)NC1=NC=CC=N1)C)C XBMURFMYQSJQEW-UHFFFAOYSA-N 0.000 description 1
- PLBHPVSXJBZKNA-UHFFFAOYSA-N 3-chloro-1-cyclopropyl-N-pyrimidin-2-ylindazol-5-amine Chemical compound ClC1=NN(C2=CC=C(C=C12)NC1=NC=CC=N1)C1CC1 PLBHPVSXJBZKNA-UHFFFAOYSA-N 0.000 description 1
- WARXKRWQWMGFJW-UHFFFAOYSA-N 3-chloro-1-cyclopropylindole Chemical compound ClC1=CN(C2=CC=CC=C12)C1CC1 WARXKRWQWMGFJW-UHFFFAOYSA-N 0.000 description 1
- LTTVIDMPCCABCQ-UHFFFAOYSA-N 3-chloro-1-propan-2-yl-N-pyrimidin-2-ylindazol-5-amine Chemical compound ClC1=NN(C2=CC=C(C=C12)NC1=NC=CC=N1)C(C)C LTTVIDMPCCABCQ-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- SRBJGELFBYXQIZ-UHFFFAOYSA-N 3-cyclopropyl-1-ethylpyrazole-4-carbaldehyde Chemical compound CCN1C=C(C=O)C(C2CC2)=N1 SRBJGELFBYXQIZ-UHFFFAOYSA-N 0.000 description 1
- DKEYCSGWKAWNRK-UHFFFAOYSA-N 3-methoxy-1-methyl-N-pyrimidin-2-ylindazol-5-amine Chemical compound COC1=NN(C2=CC=C(C=C12)NC1=NC=CC=N1)C DKEYCSGWKAWNRK-UHFFFAOYSA-N 0.000 description 1
- PAHARIHYTQTTSE-UHFFFAOYSA-N 3-methyl-1-[2-[(1-methylindol-5-yl)amino]pyrimidin-4-yl]pyrazole-4-carbaldehyde Chemical compound C1=C(C=O)C(C)=NN1C1=CC=NC(NC=2C=C3C=CN(C)C3=CC=2)=N1 PAHARIHYTQTTSE-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- DLGZLIXYVSQGOX-UHFFFAOYSA-N 4-[8-[4-(4-tert-butylpiperazin-1-yl)anilino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl]furan-2-carboxamide Chemical compound C1CN(C(C)(C)C)CCN1C(C=C1)=CC=C1NC(C1=NC=NN11)=NC=C1C1=COC(C(N)=O)=C1 DLGZLIXYVSQGOX-UHFFFAOYSA-N 0.000 description 1
- GVCLNACSYKYUHP-UHFFFAOYSA-N 4-amino-7-(2-hydroxyethoxymethyl)pyrrolo[2,3-d]pyrimidine-5-carbothioamide Chemical compound C1=NC(N)=C2C(C(=S)N)=CN(COCCO)C2=N1 GVCLNACSYKYUHP-UHFFFAOYSA-N 0.000 description 1
- OKSDAMJEAOWXSE-UHFFFAOYSA-N 4-methyl-1-[2-[(1-methylindazol-5-yl)amino]pyrimidin-4-yl]pyrrole-3-carbaldehyde Chemical compound C1=C(C=O)C(C)=CN1C1=CC=NC(NC=2C=C3C=NN(C)C3=CC=2)=N1 OKSDAMJEAOWXSE-UHFFFAOYSA-N 0.000 description 1
- MCJKSYZMURIBSI-UHFFFAOYSA-N 4-methyl-1h-indazol-5-amine Chemical compound CC1=C(N)C=CC2=C1C=NN2 MCJKSYZMURIBSI-UHFFFAOYSA-N 0.000 description 1
- CRRPZXOZFVEWCY-UHFFFAOYSA-N 4-methylpyrimidine Chemical compound CC1=CC=N[C]=N1 CRRPZXOZFVEWCY-UHFFFAOYSA-N 0.000 description 1
- NWDMGTFNIOCVDU-UHFFFAOYSA-N 5-methyl-1h-pyrazole-4-carbaldehyde Chemical compound CC=1NN=CC=1C=O NWDMGTFNIOCVDU-UHFFFAOYSA-N 0.000 description 1
- XUOLYGHNXDBYNY-UHFFFAOYSA-N 6-[[4-[(3-hydroxyazetidin-1-yl)methyl]-3-methyl-1,3-dihydropyrazol-2-yl]amino]indazole-1-carboxamide Chemical compound OC1CN(C1)CC=1C(N(NC=1)NC1=CC=C2C=NN(C2=C1)C(=O)N)C XUOLYGHNXDBYNY-UHFFFAOYSA-N 0.000 description 1
- VSSWBQMHXZBTCH-UHFFFAOYSA-N 7-(1h-pyrazol-4-yl)-1,6-naphthyridine Chemical class C1=NNC=C1C1=CC2=NC=CC=C2C=N1 VSSWBQMHXZBTCH-UHFFFAOYSA-N 0.000 description 1
- NJIAKNWTIVDSDA-FQEVSTJZSA-N 7-[4-(1-methylsulfonylpiperidin-4-yl)phenyl]-n-[[(2s)-morpholin-2-yl]methyl]pyrido[3,4-b]pyrazin-5-amine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(C=2N=C(NC[C@H]3OCCNC3)C3=NC=CN=C3C=2)C=C1 NJIAKNWTIVDSDA-FQEVSTJZSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 208000009657 Aspirin-Induced Asthma Diseases 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000714266 Bovine leukemia virus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102100040840 C-type lectin domain family 7 member A Human genes 0.000 description 1
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 1
- KGEDOJBNGRMJLD-VPHISVRJSA-N CC/C=C(\N=C(/C(/C)=C\C)\Cl)/Cl Chemical compound CC/C=C(\N=C(/C(/C)=C\C)\Cl)/Cl KGEDOJBNGRMJLD-VPHISVRJSA-N 0.000 description 1
- OVCACLXDNVIMCX-IRCKDKKWSA-N CC/C=C(\N=C(/C(/C)=C\C)\[n]1nc(C)c(C(OCC)=O)c1)/Cl Chemical compound CC/C=C(\N=C(/C(/C)=C\C)\[n]1nc(C)c(C(OCC)=O)c1)/Cl OVCACLXDNVIMCX-IRCKDKKWSA-N 0.000 description 1
- ICMDPESAODROTF-JOCHJYFZSA-N CC1=NN(C=C1CN2CC[C@H](C2)O)C3=NC(=NC=C3)NC4=CC5=C(C=C4)N(C=C5CC(C)C)C Chemical compound CC1=NN(C=C1CN2CC[C@H](C2)O)C3=NC(=NC=C3)NC4=CC5=C(C=C4)N(C=C5CC(C)C)C ICMDPESAODROTF-JOCHJYFZSA-N 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- SCJNYBYSTCRPAO-LXBQGUBHSA-N CN(C)C\C=C\C(=O)NC1=CC=C(N=C1)C(=O)N[C@@]1(C)CCC[C@H](C1)NC1=NC(C2=CNC3=CC=CC=C23)=C(Cl)C=N1 Chemical compound CN(C)C\C=C\C(=O)NC1=CC=C(N=C1)C(=O)N[C@@]1(C)CCC[C@H](C1)NC1=NC(C2=CNC3=CC=CC=C23)=C(Cl)C=N1 SCJNYBYSTCRPAO-LXBQGUBHSA-N 0.000 description 1
- DLPFQDKFXMMYTB-UHFFFAOYSA-N CN1C(N=CC=C1CN1CC(C1)O)NC=1C=C2C(=NN(C2=CC=1)C)S(=O)(=O)C Chemical compound CN1C(N=CC=C1CN1CC(C1)O)NC=1C=C2C(=NN(C2=CC=1)C)S(=O)(=O)C DLPFQDKFXMMYTB-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- DIVZNWGPRMIBBX-UHFFFAOYSA-N Cc([n](C)c(cc1)c2cc1Nc1nccc(-[n]3nc(C)c(CN(C4)CC4OC)c3)n1)c2Cl Chemical compound Cc([n](C)c(cc1)c2cc1Nc1nccc(-[n]3nc(C)c(CN(C4)CC4OC)c3)n1)c2Cl DIVZNWGPRMIBBX-UHFFFAOYSA-N 0.000 description 1
- UWQBADOPDPLPHF-UHFFFAOYSA-N Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc(cc2)cc3c2[n](CCOC)cc3)ncc1 Chemical compound Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc(cc2)cc3c2[n](CCOC)cc3)ncc1 UWQBADOPDPLPHF-UHFFFAOYSA-N 0.000 description 1
- UCXIKENKSBLXSM-UHFFFAOYSA-N Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc(cc23)ccc2[n](C)nc3Cl)ncc1 Chemical compound Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc(cc23)ccc2[n](C)nc3Cl)ncc1 UCXIKENKSBLXSM-UHFFFAOYSA-N 0.000 description 1
- WKFSTNTWRKTPFC-UHFFFAOYSA-N Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc2ccc3[n](C)cc(C(N4CCCC4)=O)c3c2)ncc1 Chemical compound Cc(c(CN(C1)CC1O)c1)n[n]1-c1nc(Nc2ccc3[n](C)cc(C(N4CCCC4)=O)c3c2)ncc1 WKFSTNTWRKTPFC-UHFFFAOYSA-N 0.000 description 1
- VLSXAYNYBJKZAV-JOCHJYFZSA-N Cc(c(CN(CC1)C[C@@H]1O)c1)n[n]1-c1nc(Nc(cc2)cc3c2[n](C2CC2)cc3C(C2CC2)=O)ncc1 Chemical compound Cc(c(CN(CC1)C[C@@H]1O)c1)n[n]1-c1nc(Nc(cc2)cc3c2[n](C2CC2)cc3C(C2CC2)=O)ncc1 VLSXAYNYBJKZAV-JOCHJYFZSA-N 0.000 description 1
- PHFOPTLWGQJGMW-SZPZYZBQSA-N Cc(c(CN(C[C@H]1O)C[C@@H]1O)c1)n[n]1-c1nc(Nc2ccc3[nH]cc(C(C4CC4)=O)c3c2)ncc1 Chemical compound Cc(c(CN(C[C@H]1O)C[C@@H]1O)c1)n[n]1-c1nc(Nc2ccc3[nH]cc(C(C4CC4)=O)c3c2)ncc1 PHFOPTLWGQJGMW-SZPZYZBQSA-N 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 206010051841 Exposure to allergen Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 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 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000883515 Homo sapiens Chitinase-3-like protein 1 Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000691614 Homo sapiens Serine/threonine-protein kinase PLK3 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 206010061246 Intervertebral disc degeneration Diseases 0.000 description 1
- 101150088608 Kdr gene Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000588655 Moraxella catarrhalis Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100237799 Mus musculus Mlkl gene Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- UZKJKOIHRZEUQL-UHFFFAOYSA-N N-(1-hydroxy-2H-pyrimidin-2-yl)-1,2-dimethylindol-5-amine Chemical compound CN1C(=CC2=CC(=CC=C12)NC1N=CC=CN1O)C UZKJKOIHRZEUQL-UHFFFAOYSA-N 0.000 description 1
- UQNQNOXDDLQJSX-UHFFFAOYSA-N N-(1-hydroxy-2H-pyrimidin-2-yl)-1-methylindol-5-amine Chemical compound CN1C=CC2=CC(=CC=C12)NC1N=CC=CN1O UQNQNOXDDLQJSX-UHFFFAOYSA-N 0.000 description 1
- FQSVLCJXPFNWCR-UHFFFAOYSA-N N-(2-methyl-1-benzofuran-5-yl)pyrimidin-2-amine Chemical compound CC=1OC2=C(C=1)C=C(C=C2)NC1=NC=CC=N1 FQSVLCJXPFNWCR-UHFFFAOYSA-N 0.000 description 1
- NHLZNHUOPTURBS-UHFFFAOYSA-N N-(3-chloro-2-methyl-1-benzofuran-5-yl)-1-hydroxy-2H-pyrimidin-2-amine Chemical compound ClC1=C(OC2=C1C=C(C=C2)NC1N=CC=CN1O)C NHLZNHUOPTURBS-UHFFFAOYSA-N 0.000 description 1
- YNUDHXPFCPFXGG-UHFFFAOYSA-N N-(5-bromopyrimidin-2-yl)-1-methylindazol-5-amine Chemical compound BrC=1C=NC(=NC=1)NC=1C=C2C=NN(C2=CC=1)C YNUDHXPFCPFXGG-UHFFFAOYSA-N 0.000 description 1
- LRLNMMURSWHHPZ-UHFFFAOYSA-N N-(5-fluoropyrimidin-2-yl)-1-methylindazol-5-amine Chemical compound FC=1C=NC(=NC=1)NC=1C=C2C=NN(C2=CC=1)C LRLNMMURSWHHPZ-UHFFFAOYSA-N 0.000 description 1
- LQVUFEYQGSXEAK-UHFFFAOYSA-N N-(5-fluoropyrimidin-2-yl)-1-propan-2-ylindazol-5-amine Chemical compound FC=1C=NC(=NC=1)NC=1C=C2C=NN(C2=CC=1)C(C)C LQVUFEYQGSXEAK-UHFFFAOYSA-N 0.000 description 1
- GCBDOWDZIRSCCK-UHFFFAOYSA-N N-(5-fluoropyrimidin-2-yl)-1-propan-2-ylindol-5-amine Chemical compound FC=1C=NC(=NC=1)NC=1C=C2C=CN(C2=CC=1)C(C)C GCBDOWDZIRSCCK-UHFFFAOYSA-N 0.000 description 1
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 1
- CUYZSFZHFHFLRE-UHFFFAOYSA-N NC(=O)c1cnc2ncc[nH]c12 Chemical class NC(=O)c1cnc2ncc[nH]c12 CUYZSFZHFHFLRE-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 235000003846 Ricinus Nutrition 0.000 description 1
- 241000322381 Ricinus <louse> Species 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- 102100026209 Serine/threonine-protein kinase PLK3 Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000014604 Specific Language disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- DRBWRJPFNOBNIO-KOLCDFICSA-N [(2r)-1-[(2r)-2-(pyridine-4-carbonylamino)propanoyl]pyrrolidin-2-yl]boronic acid Chemical compound N([C@H](C)C(=O)N1[C@@H](CCC1)B(O)O)C(=O)C1=CC=NC=C1 DRBWRJPFNOBNIO-KOLCDFICSA-N 0.000 description 1
- AMMTXBNPTNFBOD-UHFFFAOYSA-N [1-(2-chloropyrimidin-4-yl)-3-methylpyrazol-4-yl]methanol Chemical compound C1=C(CO)C(C)=NN1C1=CC=NC(Cl)=N1 AMMTXBNPTNFBOD-UHFFFAOYSA-N 0.000 description 1
- JLGYQOONCJXWME-UHFFFAOYSA-N [2-[(1-methylindazol-5-yl)amino]-2H-pyrimidin-1-yl] 2,2-dimethylpropanoate Chemical compound C(C(C)(C)C)(=O)ON1C(N=CC=C1)NC=1C=C2C=NN(C2=CC=1)C JLGYQOONCJXWME-UHFFFAOYSA-N 0.000 description 1
- 230000007488 abnormal function Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 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
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- OTKPPUXRIADSGD-PPRNARJGSA-N avoparcina Chemical compound O([C@@H]1C2=CC=C(C(=C2)Cl)OC=2C=C3C=C(C=2O[C@H]2C([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@@H]2O[C@@H](C)[C@H](O)[C@H](N)C2)OC2=CC=C(C=C2)[C@@H](O)[C@H](C(N[C@H](C(=O)N[C@H]3C(=O)N[C@H]2C(=O)N[C@@H]1C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)C=1C=CC(O)=CC=1)=O)NC(=O)[C@H](NC)C=1C=CC(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)=CC=1)[C@H]1C[C@@H](N)[C@@H](O)[C@H](C)O1 OTKPPUXRIADSGD-PPRNARJGSA-N 0.000 description 1
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000023819 chronic asthma Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 206010072757 chronic spontaneous urticaria Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl 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
- VUAQDGAQHZEJRI-LJQANCHMSA-N cyclopropyl-[5-[[4-[4-[[(3r)-3-hydroxypyrrolidin-1-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1h-indol-3-yl]methanone Chemical compound CC1=NN(C=2N=C(NC=3C=C4C(C(=O)C5CC5)=CNC4=CC=3)N=CC=2)C=C1CN1CC[C@@H](O)C1 VUAQDGAQHZEJRI-LJQANCHMSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 108010025838 dectin 1 Proteins 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- DFBKLUNHFCTMDC-GKRDHZSOSA-N endrin Chemical compound C([C@@H]1[C@H]2[C@@]3(Cl)C(Cl)=C([C@]([C@H]22)(Cl)C3(Cl)Cl)Cl)[C@@H]2[C@H]2[C@@H]1O2 DFBKLUNHFCTMDC-GKRDHZSOSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- PCMGHESDZDBXAO-UHFFFAOYSA-N ethyl 1-(2-chloro-5-methylpyrimidin-4-yl)-3-methylpyrazole-4-carboxylate Chemical compound N1=C(C)C(C(=O)OCC)=CN1C1=NC(Cl)=NC=C1C PCMGHESDZDBXAO-UHFFFAOYSA-N 0.000 description 1
- QSQQBPVWBVSKBJ-UHFFFAOYSA-N ethyl 1-(2-chloropyrimidin-4-yl)-3-cyclopropylpyrazole-4-carboxylate Chemical compound CCOC(=O)C1=CN(C=2N=C(Cl)N=CC=2)N=C1C1CC1 QSQQBPVWBVSKBJ-UHFFFAOYSA-N 0.000 description 1
- MMDOYVVZUVZLHQ-UHFFFAOYSA-N ethyl 4-methyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CNC=C1C MMDOYVVZUVZLHQ-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003304 gavage Methods 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
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 102000054350 human CHI3L1 Human genes 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000007794 irritation Effects 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
- 230000008407 joint function Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229960004635 mesna Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- IHCHOVVAJBADAH-UHFFFAOYSA-N n-[2-hydroxy-4-(1h-pyrazol-4-yl)phenyl]-6-methoxy-3,4-dihydro-2h-chromene-3-carboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1C(=O)NC(C(=C1)O)=CC=C1C=1C=NNC=1 IHCHOVVAJBADAH-UHFFFAOYSA-N 0.000 description 1
- LPOIGVZLNWEGJG-UHFFFAOYSA-N n-benzyl-5-(4-methylpiperazin-1-yl)-2-nitroaniline Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(NCC=2C=CC=CC=2)=C1 LPOIGVZLNWEGJG-UHFFFAOYSA-N 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- VFEPFSLUHQWVNT-UHFFFAOYSA-N naphthalene-1-sulfonic acid;naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21.C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 VFEPFSLUHQWVNT-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 230000006884 regulation of angiogenesis Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000003506 spasmogen Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006459 vascular development Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Otolaryngology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261588793P | 2012-01-20 | 2012-01-20 | |
| US61/588,793 | 2012-01-20 | ||
| PCT/US2013/022135 WO2013109882A1 (en) | 2012-01-20 | 2013-01-18 | Substituted pyrimidine compounds and their use as syk inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20140135954A KR20140135954A (ko) | 2014-11-27 |
| KR101944914B1 true KR101944914B1 (ko) | 2019-02-07 |
Family
ID=48799685
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147023266A Active KR101944914B1 (ko) | 2012-01-20 | 2013-01-18 | 치환된 피리미딘 화합물 및 syk 억제제로서의 이의 용도 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8871778B2 (enExample) |
| EP (1) | EP2804861B1 (enExample) |
| JP (1) | JP6062962B2 (enExample) |
| KR (1) | KR101944914B1 (enExample) |
| CN (1) | CN104203943B (enExample) |
| AU (1) | AU2013209586B2 (enExample) |
| CA (1) | CA2863517C (enExample) |
| ES (1) | ES2668479T3 (enExample) |
| NZ (1) | NZ627113A (enExample) |
| PL (1) | PL2804861T3 (enExample) |
| WO (1) | WO2013109882A1 (enExample) |
| ZA (1) | ZA201406038B (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE056048T2 (hu) * | 2013-10-21 | 2022-01-28 | Genosco | Helyettesített pirimidin vegyületek és SYK inhibitorként való alkalmazásuk |
| CN103969445B (zh) * | 2014-05-08 | 2015-09-30 | 中南大学 | 亚铁血红素—二氧化锰复合物的制备及其用于检测人IgG的方法 |
| TWI730331B (zh) | 2014-10-13 | 2021-06-11 | 南韓商柳韓洋行股份有限公司 | 用於調節ｅｇｆｒ突變型激酶活性的化合物及組成物 |
| PL3240785T3 (pl) | 2014-12-29 | 2021-12-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inhibitory drobnocząsteczkowe dehydrogenazy mleczanowej i sposoby ich wykorzystania |
| CN110678461B (zh) * | 2017-06-14 | 2021-08-10 | 正大天晴药业集团股份有限公司 | Syk抑制剂及其使用方法 |
| JP7189932B2 (ja) * | 2017-07-28 | 2022-12-14 | ユハン コーポレーション | タンパク質キナーゼに対する選択的阻害剤の合成に有用な中間体及びそれを調製するためのプロセス |
| CA3134261A1 (en) | 2019-03-19 | 2020-09-24 | Voronoi Inc. | 6-(isooxazolidin-2-yl)-n-phenylpyrimidin-4-amine derivatives as inhibitors of epidermal growth factor receptors |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| 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 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| KR20210152312A (ko) * | 2020-06-08 | 2021-12-15 | 주식회사 종근당 | 카나비노이드 수용체 (cb1 수용체) 길항제로서의 4-(4,5-디하이드로-1h-피라졸-1-닐)피리미딘 화합물 및 이를 포함하는 약제학적 조성물 |
| EP4217354A1 (en) * | 2020-09-23 | 2023-08-02 | Nerviano Medical Sciences S.r.l. | Pyrazolyl-pyrimidine derivatives as kinase inhibitors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011060295A1 (en) * | 2009-11-13 | 2011-05-19 | Genosco | Kinase inhibitors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0923581T3 (da) * | 1996-08-09 | 2003-08-04 | Boehringer Ingelheim Pharma | 4-substituerede beta-carboliner som immunmodulatorer |
| WO2004087698A2 (en) * | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| TW201016676A (en) * | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| JP5959537B2 (ja) * | 2011-01-28 | 2016-08-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換ピリジニル−ピリミジン及び医薬としてのその使用 |
-
2013
- 2013-01-18 KR KR1020147023266A patent/KR101944914B1/ko active Active
- 2013-01-18 US US13/745,734 patent/US8871778B2/en active Active
- 2013-01-18 CA CA2863517A patent/CA2863517C/en active Active
- 2013-01-18 ES ES13738382.4T patent/ES2668479T3/es active Active
- 2013-01-18 JP JP2014553451A patent/JP6062962B2/ja active Active
- 2013-01-18 AU AU2013209586A patent/AU2013209586B2/en active Active
- 2013-01-18 PL PL13738382T patent/PL2804861T3/pl unknown
- 2013-01-18 WO PCT/US2013/022135 patent/WO2013109882A1/en not_active Ceased
- 2013-01-18 EP EP13738382.4A patent/EP2804861B1/en active Active
- 2013-01-18 CN CN201380015041.1A patent/CN104203943B/zh active Active
- 2013-01-18 NZ NZ627113A patent/NZ627113A/en unknown
-
2014
- 2014-08-18 ZA ZA2014/06038A patent/ZA201406038B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011060295A1 (en) * | 2009-11-13 | 2011-05-19 | Genosco | Kinase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2863517A1 (en) | 2013-07-25 |
| AU2013209586A1 (en) | 2014-07-24 |
| WO2013109882A1 (en) | 2013-07-25 |
| ES2668479T3 (es) | 2018-05-18 |
| JP2015504093A (ja) | 2015-02-05 |
| US8871778B2 (en) | 2014-10-28 |
| AU2013209586B2 (en) | 2017-08-17 |
| EP2804861A4 (en) | 2015-07-22 |
| KR20140135954A (ko) | 2014-11-27 |
| CN104203943B (zh) | 2017-12-29 |
| CN104203943A (zh) | 2014-12-10 |
| US20130274242A1 (en) | 2013-10-17 |
| HK1205106A1 (en) | 2015-12-11 |
| PL2804861T3 (pl) | 2018-08-31 |
| CA2863517C (en) | 2019-11-05 |
| NZ627113A (en) | 2016-07-29 |
| ZA201406038B (en) | 2015-12-23 |
| JP6062962B2 (ja) | 2017-01-18 |
| EP2804861B1 (en) | 2018-02-28 |
| EP2804861A1 (en) | 2014-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101944914B1 (ko) | 치환된 피리미딘 화합물 및 syk 억제제로서의 이의 용도 | |
| EP2498607B1 (en) | Kinase inhibitors | |
| US9567342B2 (en) | Certain protein kinase inhibitors | |
| KR102011770B1 (ko) | 치환된 피리도피리미딘 화합물 및 flt3 억제제로서의 이의 용도 | |
| CA3134261A1 (en) | 6-(isooxazolidin-2-yl)-n-phenylpyrimidin-4-amine derivatives as inhibitors of epidermal growth factor receptors | |
| KR102228034B1 (ko) | 치환된 피리미딘 화합물 및 syk 억제제로서의 이의 용도 | |
| KR20090092317A (ko) | 키나제 억제제로서의 화합물 및 조성물 | |
| CA3161339A1 (en) | Cyclic compounds and methods of using same | |
| JP2022547294A (ja) | キナーゼ阻害剤としての３，５－ジ置換ピラゾール化合物およびその応用 | |
| JP6483656B2 (ja) | キナーゼ活性のモジュレータとしての６−［４−（１ｈ−イミダゾール−２−イル）ピペリジン−１−イル］ピリミジン−４−アミン誘導体 | |
| CN101489559A (zh) | 作为药物化合物的嘌呤和脱氮嘌呤衍生物 | |
| HK1205106B (en) | Substituted pyrimidine compounds and their use as syk inhibitors | |
| WO2024254490A1 (en) | Pyrazolo-pyrimidinone compounds for use in methods of inhibiting wee1 a kinase | |
| HK1226395B (en) | Substituted pyrimidine compounds and their use as syk inhibitors | |
| BR112016008060B1 (pt) | Composto, formulação farmacêutica, processo para preparar um composto de fórmula (i), método para preparação de um composto, uso do composto ou sal farmaceuticamente aceitável do mesmo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20140820 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20170207 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180321 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20181026 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20190128 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20190129 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20220117 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20221221 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20250121 Start annual number: 7 End annual number: 7 |