HU228502B1 - Indazole derivatives and pharmaceutical compositions for inhibiting protein kinases, and methods for their use - Google Patents
Indazole derivatives and pharmaceutical compositions for inhibiting protein kinases, and methods for their use Download PDFInfo
- Publication number
- HU228502B1 HU228502B1 HU0202490A HUP0202490A HU228502B1 HU 228502 B1 HU228502 B1 HU 228502B1 HU 0202490 A HU0202490 A HU 0202490A HU P0202490 A HUP0202490 A HU P0202490A HU 228502 B1 HU228502 B1 HU 228502B1
- Authority
- HU
- Hungary
- Prior art keywords
- substituted
- alkyl
- found
- compound
- aryl
- Prior art date
Links
- 102000001253 Protein Kinase Human genes 0.000 title claims description 29
- 108060006633 protein kinase Proteins 0.000 title claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 238000000034 method Methods 0.000 title description 61
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 427
- -1 helerocycloalkyl Chemical group 0.000 claims description 283
- 125000003118 aryl group Chemical group 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 230000000694 effects Effects 0.000 claims description 38
- 108091000080 Phosphotransferase Proteins 0.000 claims description 26
- 102000020233 phosphotransferase Human genes 0.000 claims description 26
- 229920006395 saturated elastomer Polymers 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 19
- 239000001301 oxygen Substances 0.000 claims description 19
- 239000011593 sulfur Substances 0.000 claims description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 230000033115 angiogenesis Effects 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 108091008605 VEGF receptors Proteins 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 2
- 101150065749 Churc1 gene Proteins 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 102100038239 Protein Churchill Human genes 0.000 claims description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 2
- 230000032823 cell division Effects 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 6
- 125000003107 substituted aryl group Chemical group 0.000 claims 6
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims 2
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 claims 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 1
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000003367 polycyclic group Chemical group 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 666
- 238000005481 NMR spectroscopy Methods 0.000 description 348
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 325
- 235000019439 ethyl acetate Nutrition 0.000 description 228
- 239000000243 solution Substances 0.000 description 216
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- 239000000203 mixture Substances 0.000 description 166
- 238000006243 chemical reaction Methods 0.000 description 123
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
- 239000007787 solid Substances 0.000 description 100
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 96
- 229910001868 water Inorganic materials 0.000 description 95
- 239000011541 reaction mixture Substances 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 79
- 230000002829 reductive effect Effects 0.000 description 71
- 238000000921 elemental analysis Methods 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 66
- 238000010898 silica gel chromatography Methods 0.000 description 66
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 64
- 239000007858 starting material Substances 0.000 description 62
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 61
- 229910052938 sodium sulfate Inorganic materials 0.000 description 55
- 235000011152 sodium sulphate Nutrition 0.000 description 55
- 239000012267 brine Substances 0.000 description 54
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 52
- 239000002253 acid Substances 0.000 description 52
- 229910052786 argon Inorganic materials 0.000 description 48
- 239000012044 organic layer Substances 0.000 description 47
- 239000003921 oil Substances 0.000 description 46
- 235000019198 oils Nutrition 0.000 description 46
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 46
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 39
- 238000000746 purification Methods 0.000 description 39
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- 238000003756 stirring Methods 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 29
- 229910002027 silica gel Inorganic materials 0.000 description 29
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
- 206010028980 Neoplasm Diseases 0.000 description 28
- 238000002360 preparation method Methods 0.000 description 27
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 26
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 23
- 239000000377 silicon dioxide Substances 0.000 description 23
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000003480 eluent Substances 0.000 description 21
- 229920002554 vinyl polymer Polymers 0.000 description 21
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 20
- 201000011510 cancer Diseases 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- 239000000126 substance Substances 0.000 description 19
- 239000010409 thin film Substances 0.000 description 19
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 239000011368 organic material Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 238000004809 thin layer chromatography Methods 0.000 description 14
- 108091007914 CDKs Proteins 0.000 description 13
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 13
- VFMGOJUUTAPPDA-UHFFFAOYSA-N 2-ethyl-5-methylpyrazole-3-carboxylic acid Chemical compound CCN1N=C(C)C=C1C(O)=O VFMGOJUUTAPPDA-UHFFFAOYSA-N 0.000 description 12
- UYDGNRLMYZMDOG-UHFFFAOYSA-N 5-methyl-1,3-thiazole-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)S1 UYDGNRLMYZMDOG-UHFFFAOYSA-N 0.000 description 12
- 102100034741 Cyclin-dependent kinase 20 Human genes 0.000 description 12
- 101500014379 Lymnaea stagnalis Ovulation hormone Proteins 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000011161 development Methods 0.000 description 12
- 230000018109 developmental process Effects 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 239000005711 Benzoic acid Substances 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 230000022131 cell cycle Effects 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 240000003291 Armoracia rusticana Species 0.000 description 10
- 239000007821 HATU Substances 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000000969 carrier Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 235000011330 Armoracia rusticana Nutrition 0.000 description 9
- 239000005977 Ethylene Substances 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 235000010233 benzoic acid Nutrition 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000006184 cosolvent Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-QYKNYGDISA-N 2-deuteriopyridine Chemical compound [2H]C1=CC=CC=N1 JUJWROOIHBZHMG-QYKNYGDISA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 7
- 239000000654 additive Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 230000004663 cell proliferation Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 6
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 102000016736 Cyclin Human genes 0.000 description 6
- 108050006400 Cyclin Proteins 0.000 description 6
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 6
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000005518 carboxamido group Chemical group 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 230000004992 fission Effects 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
- YANIJISPXQRULY-UHFFFAOYSA-N 4-[3-(1H-indol-2-yl)-1H-indazol-6-yl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC(C=2C=C3NN=C(C3=CC=2)C=2NC3=CC=CC=C3C=2)=C1 YANIJISPXQRULY-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 5
- 231100000277 DNA damage Toxicity 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 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 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
- 150000001299 aldehydes Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000005587 bubbling Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 125000005469 ethylenyl group Chemical group 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 150000007522 mineralic acids Chemical class 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- QRWZFUBHOQWUGH-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(C)N=1 QRWZFUBHOQWUGH-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000012746 DNA damage checkpoint Effects 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 4
- 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 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ROGHUJUFCRFUSO-UHFFFAOYSA-N 1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CN2 ROGHUJUFCRFUSO-UHFFFAOYSA-N 0.000 description 3
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
- SMFHPCZZAAMJJO-UHFFFAOYSA-N 2-chloro-5-methylphenol Chemical compound CC1=CC=C(Cl)C(O)=C1 SMFHPCZZAAMJJO-UHFFFAOYSA-N 0.000 description 3
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- 229920002527 Glycogen Polymers 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 101100290051 Malus domestica MALD1 gene Proteins 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- 102000014750 Phosphorylase Kinase Human genes 0.000 description 3
- 108010064071 Phosphorylase Kinase Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 229940096919 glycogen Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 239000008241 heterogeneous mixture Substances 0.000 description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
- 231100000053 low toxicity Toxicity 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 239000011777 magnesium Chemical class 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- AQFWNELGMODZGC-UHFFFAOYSA-N o-ethylhydroxylamine Chemical compound CCON AQFWNELGMODZGC-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000011591 potassium Chemical class 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000003909 protein kinase inhibitor Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 210000004127 vitreous body Anatomy 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 2
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- GJDJNLKPKHOBSN-UHFFFAOYSA-N 2-amino-n-methyl-3-nitrobenzamide Chemical compound CNC(=O)C1=CC=CC([N+]([O-])=O)=C1N GJDJNLKPKHOBSN-UHFFFAOYSA-N 0.000 description 2
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
- LLWADFLAOKUBDR-UHFFFAOYSA-N 2-methyl-4-chlorophenoxybutyric acid Chemical compound CC1=CC(Cl)=CC=C1OCCCC(O)=O LLWADFLAOKUBDR-UHFFFAOYSA-N 0.000 description 2
- AYEGPMGNMOIHDL-UHFFFAOYSA-N 2-methylcyclopropane-1-carboxylic acid Chemical compound CC1CC1C(O)=O AYEGPMGNMOIHDL-UHFFFAOYSA-N 0.000 description 2
- AMQIPHZFLIDOCB-UHFFFAOYSA-N 3-(2-hydroxyethyl)phenol Chemical compound OCCC1=CC=CC(O)=C1 AMQIPHZFLIDOCB-UHFFFAOYSA-N 0.000 description 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 2
- AHXXIALEMINDAW-UHFFFAOYSA-N 4-(methoxymethyl)phenol Chemical compound COCC1=CC=C(O)C=C1 AHXXIALEMINDAW-UHFFFAOYSA-N 0.000 description 2
- WHSIIJQOEGXWSN-UHFFFAOYSA-N 4-bromo-2-methoxyphenol Chemical compound COC1=CC(Br)=CC=C1O WHSIIJQOEGXWSN-UHFFFAOYSA-N 0.000 description 2
- CODFXJPNZHQAQN-UHFFFAOYSA-N 4-bromo-3-(2-hydroxyethyl)phenol Chemical compound OCCC1=CC(O)=CC=C1Br CODFXJPNZHQAQN-UHFFFAOYSA-N 0.000 description 2
- AYPCLZDGADHRDL-UHFFFAOYSA-N 5-ethyl-2-methylpyrazole-3-carboxylic acid Chemical compound CCC=1C=C(C(O)=O)N(C)N=1 AYPCLZDGADHRDL-UHFFFAOYSA-N 0.000 description 2
- AUZHMOQAPWTGTB-UHFFFAOYSA-N 5-methyl-2-propan-2-ylpyrazole-3-carboxylic acid Chemical compound CC(C)N1N=C(C)C=C1C(O)=O AUZHMOQAPWTGTB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 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 2
- 102000009088 Angiopoietin-1 Human genes 0.000 description 2
- 108010048154 Angiopoietin-1 Proteins 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 108010058546 Cyclin D1 Proteins 0.000 description 2
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 2
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 2
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 2
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 2
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 2
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 2
- TWHFSFMHMFBJRP-UHFFFAOYSA-N N-[3-[3-(1H-imidazo[4,5-b]pyridin-2-yl)-1H-indazole-6-carbonyl]phenyl]benzamide Chemical compound C=1C=CC(C(=O)C=2C=C3NN=C(C3=CC=2)C=2NC3=NC=CC=C3N=2)=CC=1NC(=O)C1=CC=CC=C1 TWHFSFMHMFBJRP-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 2
- 229960004012 amifampridine Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 230000006369 cell cycle progression Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical group NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 150000002496 iodine Chemical class 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 210000000554 iris Anatomy 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- WOIOUPCWKZMWJN-UHFFFAOYSA-N prop-2-enoyl chloride hydrochloride Chemical compound Cl.ClC(=O)C=C WOIOUPCWKZMWJN-UHFFFAOYSA-N 0.000 description 2
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- 150000003385 sodium Chemical class 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 150000003464 sulfur compounds Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- YGRARUNSCNUDNB-UHFFFAOYSA-N (2-ethylphenyl)-diphenylphosphane Chemical compound CCC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YGRARUNSCNUDNB-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- RCVDPBFUMYUKPB-UHFFFAOYSA-N (3,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1OC RCVDPBFUMYUKPB-UHFFFAOYSA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- HGPQAWTZLJXCTC-SSTWWWIQSA-N (4r,4ar,7s,7ar,12bs)-7,9-dimethoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline Chemical compound C([C@@H](N(CC1)C)[C@@H]2C=C[C@@H]3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 HGPQAWTZLJXCTC-SSTWWWIQSA-N 0.000 description 1
- OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 description 1
- ZFOVCSTVYYYRSU-ZZXKWVIFSA-N (e)-3-(4-chlorophenyl)prop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=C(Cl)C=C1 ZFOVCSTVYYYRSU-ZZXKWVIFSA-N 0.000 description 1
- IMRILMSKMWAKCC-ONEGZZNKSA-N (e)-3-(furan-2-yl)prop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CO1 IMRILMSKMWAKCC-ONEGZZNKSA-N 0.000 description 1
- SOFYBDFGCNVMML-FXRZFVDSSA-N (e)-3-pyridin-2-ylprop-2-enoyl chloride;hydrochloride Chemical compound Cl.ClC(=O)\C=C\C1=CC=CC=N1 SOFYBDFGCNVMML-FXRZFVDSSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- MIIQJAUWHSUTIT-UHFFFAOYSA-N 1,2-oxazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=NO1 MIIQJAUWHSUTIT-UHFFFAOYSA-N 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- XLHUBROMZOAQMV-UHFFFAOYSA-N 1,4-benzosemiquinone Chemical group [O]C1=CC=C(O)C=C1 XLHUBROMZOAQMV-UHFFFAOYSA-N 0.000 description 1
- PXRXGHUTKHXUGF-UHFFFAOYSA-N 1,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1C PXRXGHUTKHXUGF-UHFFFAOYSA-N 0.000 description 1
- QIBOGVKBYVXIAY-UHFFFAOYSA-N 1-(1h-benzimidazol-2-yl)indazole Chemical compound C12=CC=CC=C2C=NN1C1=NC2=CC=CC=C2N1 QIBOGVKBYVXIAY-UHFFFAOYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- UJXJOVMQUWMGQB-UHFFFAOYSA-N 1-chloro-2-(2-methylphenyl)benzene Chemical compound CC1=CC=CC=C1C1=CC=CC=C1Cl UJXJOVMQUWMGQB-UHFFFAOYSA-N 0.000 description 1
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical class [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
- FSWUGFSHWYDKTO-UHFFFAOYSA-N 1-ethyl-3-methylpyrazole Chemical compound CCN1C=CC(C)=N1 FSWUGFSHWYDKTO-UHFFFAOYSA-N 0.000 description 1
- JINZWCUGPDJTNB-UHFFFAOYSA-N 1-ethylimidazole-2-carbaldehyde Chemical compound CCN1C=CN=C1C=O JINZWCUGPDJTNB-UHFFFAOYSA-N 0.000 description 1
- IDHMTYNXPJWISA-UHFFFAOYSA-N 1-ethylpiperidin-1-ium-4-carboxylate Chemical compound CCN1CCC(C(O)=O)CC1 IDHMTYNXPJWISA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WLDPWZQYAVZTTP-UHFFFAOYSA-N 1-methyl-imidazole-2-carboxylic acid Chemical compound CN1C=CN=C1C(O)=O WLDPWZQYAVZTTP-UHFFFAOYSA-N 0.000 description 1
- JREJQAWGQCMSIY-UHFFFAOYSA-N 1-methyl-pyrazole-5-carboxylic acid Chemical compound CN1N=CC=C1C(O)=O JREJQAWGQCMSIY-UHFFFAOYSA-N 0.000 description 1
- UEBFLTZXUXZPJO-UHFFFAOYSA-N 1-methylimidazole-2-carbaldehyde Chemical compound CN1C=CN=C1C=O UEBFLTZXUXZPJO-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 1
- JVTSHOJDBRTPHD-UHFFFAOYSA-N 2,2,2-trifluoroacetaldehyde Chemical compound FC(F)(F)C=O JVTSHOJDBRTPHD-UHFFFAOYSA-N 0.000 description 1
- QQHQTDXPCVOKMA-UHFFFAOYSA-N 2,3-diamino-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(N)=C1N QQHQTDXPCVOKMA-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
- BKYWPNROPGQIFZ-UHFFFAOYSA-N 2,4-dimethylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C(C)=C1 BKYWPNROPGQIFZ-UHFFFAOYSA-N 0.000 description 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
- AMCOCUDBDKVWRZ-UHFFFAOYSA-N 2-(2-hydroxyethoxy)phenol Chemical compound OCCOC1=CC=CC=C1O AMCOCUDBDKVWRZ-UHFFFAOYSA-N 0.000 description 1
- PDFGFQUSSYSWNI-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1CBr PDFGFQUSSYSWNI-UHFFFAOYSA-N 0.000 description 1
- QRZPZGBEAWFDDR-UHFFFAOYSA-N 2-(chloromethyl)pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(CCl)=C1 QRZPZGBEAWFDDR-UHFFFAOYSA-N 0.000 description 1
- YBXREKNEMXXRPL-UHFFFAOYSA-N 2-(indazol-1-ylmethoxy)ethyl-trimethylsilane Chemical compound C1=CC=C2N(COCC[Si](C)(C)C)N=CC2=C1 YBXREKNEMXXRPL-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- QBMKTNPVTMKYFL-UHFFFAOYSA-N 2-[(3-iodo-6-nitroindazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound C1=C([N+]([O-])=O)C=C2N(COCC[Si](C)(C)C)N=C(I)C2=C1 QBMKTNPVTMKYFL-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- MXSKDZXIGAALAW-UHFFFAOYSA-N 2-[[3-ethenyl-4-(2-nitrophenyl)indazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)C1=C2C(=NN(C2=CC=C1)COCC[Si](C)(C)C)C=C MXSKDZXIGAALAW-UHFFFAOYSA-N 0.000 description 1
- PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 1
- VKDFZMMOLPIWQQ-UHFFFAOYSA-N 2-acetamido-2-phenylacetic acid Chemical compound CC(=O)NC(C(O)=O)C1=CC=CC=C1 VKDFZMMOLPIWQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- APSMUYYLXZULMS-UHFFFAOYSA-N 2-bromonaphthalene Chemical compound C1=CC=CC2=CC(Br)=CC=C21 APSMUYYLXZULMS-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- QXCOHSRHFCHCHN-UHFFFAOYSA-N 2-chloropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=C1 QXCOHSRHFCHCHN-UHFFFAOYSA-N 0.000 description 1
- BPGIOCZAQDIBPI-UHFFFAOYSA-N 2-ethoxyethanamine Chemical compound CCOCCN BPGIOCZAQDIBPI-UHFFFAOYSA-N 0.000 description 1
- MEBDLVFZCYEUFR-UHFFFAOYSA-N 2-ethyl-1-methyl-3h-pyrazole Chemical compound CCN1CC=CN1C MEBDLVFZCYEUFR-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- NBPPFCOVAKZVCC-UHFFFAOYSA-N 2-hydroxy-6-methylbenzenesulfonamide Chemical compound CC1=CC=CC(O)=C1S(N)(=O)=O NBPPFCOVAKZVCC-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- PQFOUIMVTGBFRN-UHFFFAOYSA-N 2-isocyanato-1-methyl-4-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1N=C=O PQFOUIMVTGBFRN-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 1
- VXDHQYLFEYUMFY-UHFFFAOYSA-N 2-methylprop-2-en-1-amine Chemical compound CC(=C)CN VXDHQYLFEYUMFY-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HVLUYXIJZLDNIS-UHFFFAOYSA-N 2-thiophen-2-ylethanamine Chemical compound NCCC1=CC=CS1 HVLUYXIJZLDNIS-UHFFFAOYSA-N 0.000 description 1
- NIDVTZFOPMJWNH-UHFFFAOYSA-N 2-trimethylsilylethyl n-(2-fluoro-5-nitrophenyl)carbamate Chemical compound C[Si](C)(C)CCOC(=O)NC1=CC([N+]([O-])=O)=CC=C1F NIDVTZFOPMJWNH-UHFFFAOYSA-N 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
- CUECQYFYMGJLJD-UHFFFAOYSA-N 3-(dimethylamino)benzoyl chloride Chemical compound CN(C)C1=CC=CC(C(Cl)=O)=C1 CUECQYFYMGJLJD-UHFFFAOYSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-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
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UICOGKGYSA-N 3-deuterio-1H-indazole Chemical compound N1N=C(C2=CC=CC=C12)[2H] BAXOFTOLAUCFNW-UICOGKGYSA-N 0.000 description 1
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- GZCGNGLOCQEDMT-UHFFFAOYSA-N 3-iodo-6-nitro-2h-indazole Chemical compound [O-][N+](=O)C1=CC=C2C(I)=NNC2=C1 GZCGNGLOCQEDMT-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- HXIYCKAAQPHZBM-UHFFFAOYSA-N 3-methyl-1,2-oxazole-5-carboxylic acid Chemical compound CC=1C=C(C(O)=O)ON=1 HXIYCKAAQPHZBM-UHFFFAOYSA-N 0.000 description 1
- ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 1
- GBSRFNJOYKWQBR-UHFFFAOYSA-N 3-phenoxycyclohex-2-en-1-one Chemical compound O=C1CCCC(OC=2C=CC=CC=2)=C1 GBSRFNJOYKWQBR-UHFFFAOYSA-N 0.000 description 1
- QMGBIPKOKCSUCL-UHFFFAOYSA-N 3-propan-2-yloxyaniline Chemical compound CC(C)OC1=CC=CC(N)=C1 QMGBIPKOKCSUCL-UHFFFAOYSA-N 0.000 description 1
- BFWYZZPDZZGSLJ-UHFFFAOYSA-N 4-(aminomethyl)aniline Chemical compound NCC1=CC=C(N)C=C1 BFWYZZPDZZGSLJ-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
- FHIRTCZQNMPCJR-UHFFFAOYSA-N 4-bromo-2-ethoxyphenol Chemical compound CCOC1=CC(Br)=CC=C1O FHIRTCZQNMPCJR-UHFFFAOYSA-N 0.000 description 1
- JDGOYQOXCIBZRX-UHFFFAOYSA-N 4-bromo-2-methoxy-5-methylphenol Chemical compound COC1=CC(Br)=C(C)C=C1O JDGOYQOXCIBZRX-UHFFFAOYSA-N 0.000 description 1
- FCRCHBBRZJZSHO-UHFFFAOYSA-N 4-bromo-2-phenylmethoxyphenol Chemical compound OC1=CC=C(Br)C=C1OCC1=CC=CC=C1 FCRCHBBRZJZSHO-UHFFFAOYSA-N 0.000 description 1
- WMUWDPLTTLJNPE-UHFFFAOYSA-N 4-bromo-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Br WMUWDPLTTLJNPE-UHFFFAOYSA-N 0.000 description 1
- HLSGKNUHUDYLGD-UHFFFAOYSA-N 4-bromo-3-chloro-5-methylphenol Chemical compound CC1=CC(O)=CC(Cl)=C1Br HLSGKNUHUDYLGD-UHFFFAOYSA-N 0.000 description 1
- GPOQODYGMUTOQL-UHFFFAOYSA-N 4-bromo-3-methylphenol Chemical compound CC1=CC(O)=CC=C1Br GPOQODYGMUTOQL-UHFFFAOYSA-N 0.000 description 1
- GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 1
- NNMYRMGMVLMQAY-UHFFFAOYSA-N 4-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC=N1 NNMYRMGMVLMQAY-UHFFFAOYSA-N 0.000 description 1
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- SIRFVGWDRUJXAR-UHFFFAOYSA-N 4-nitro-2h-phthalazin-1-one Chemical compound C1=CC=C2C([N+](=O)[O-])=NNC(=O)C2=C1 SIRFVGWDRUJXAR-UHFFFAOYSA-N 0.000 description 1
- OWNLZVDXQOGVDK-UHFFFAOYSA-N 4-piperazin-1-yl-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1N1CCNCC1 OWNLZVDXQOGVDK-UHFFFAOYSA-N 0.000 description 1
- NOMWSIXEERHDSY-UHFFFAOYSA-N 4h-indazole Chemical compound C1C=CC=C2N=NC=C12 NOMWSIXEERHDSY-UHFFFAOYSA-N 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- RNPLRYOXDQXYCM-UHFFFAOYSA-N 5-ethyl-1,3-thiazole-2-carboxylic acid Chemical compound CCC1=CN=C(C(O)=O)S1 RNPLRYOXDQXYCM-UHFFFAOYSA-N 0.000 description 1
- CZQRECSXIZVKQT-UHFFFAOYSA-N 5-methyl-2-propylpyrazole-3-carboxamide Chemical compound CCCN1N=C(C)C=C1C(N)=O CZQRECSXIZVKQT-UHFFFAOYSA-N 0.000 description 1
- HQMYLVSSRJVINL-UHFFFAOYSA-N 5-methyl-n-[3-[methyl-[3-(2-phenylethenyl)-1h-indazol-6-yl]amino]phenyl]-1,3-thiazole-2-carboxamide Chemical compound C=1C=C2C(C=CC=3C=CC=CC=3)=NNC2=CC=1N(C)C(C=1)=CC=CC=1NC(=O)C1=NC=C(C)S1 HQMYLVSSRJVINL-UHFFFAOYSA-N 0.000 description 1
- WSMQKESQZFQMFW-UHFFFAOYSA-N 5-methyl-pyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1 WSMQKESQZFQMFW-UHFFFAOYSA-N 0.000 description 1
- DJDHHXDFKSLEQY-UHFFFAOYSA-N 5-methylpyridine-3-carboxylic acid Chemical compound CC1=CN=CC(C(O)=O)=C1 DJDHHXDFKSLEQY-UHFFFAOYSA-N 0.000 description 1
- SLWRTVINHWIGTK-UHFFFAOYSA-N 5-methylsulfonylthiophene-2-carboxylic acid Chemical compound CS(=O)(=O)C1=CC=C(C(O)=O)S1 SLWRTVINHWIGTK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- WTURPCPLLDSGHW-JLHYYAGUSA-N 6-[3-(methoxymethoxy)phenoxy]-3-[(e)-2-phenylethenyl]-1h-indazole Chemical compound COCOC1=CC=CC(OC=2C=C3NN=C(\C=C\C=4C=CC=CC=4)C3=CC=2)=C1 WTURPCPLLDSGHW-JLHYYAGUSA-N 0.000 description 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
- PJDDMGACZRXMEN-UHFFFAOYSA-N 6-pyridin-4-yl-1-(2-trimethylsilylethoxymethyl)indazole-3-carbaldehyde Chemical compound C1=C2N(COCC[Si](C)(C)C)N=C(C=O)C2=CC=C1C1=CC=NC=C1 PJDDMGACZRXMEN-UHFFFAOYSA-N 0.000 description 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
- IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 240000007087 Apium graveolens Species 0.000 description 1
- 235000015849 Apium graveolens Dulce Group Nutrition 0.000 description 1
- 235000010591 Appio Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010051113 Arterial restenosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- RFVYQWYNYFCXQL-UHFFFAOYSA-N C1=CC=CC2=CC([Li])=CC=C21 Chemical compound C1=CC=CC2=CC([Li])=CC=C21 RFVYQWYNYFCXQL-UHFFFAOYSA-N 0.000 description 1
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 101150012716 CDK1 gene Proteins 0.000 description 1
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 101710150820 Cellular tumor antigen p53 Proteins 0.000 description 1
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010068192 Cyclin A Proteins 0.000 description 1
- 108010060385 Cyclin B1 Proteins 0.000 description 1
- 108010060387 Cyclin B2 Proteins 0.000 description 1
- 102000003910 Cyclin D Human genes 0.000 description 1
- 108090000259 Cyclin D Proteins 0.000 description 1
- 108010058544 Cyclin D2 Proteins 0.000 description 1
- 102000006313 Cyclin D3 Human genes 0.000 description 1
- 108010058545 Cyclin D3 Proteins 0.000 description 1
- 102000003909 Cyclin E Human genes 0.000 description 1
- 108090000257 Cyclin E Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- SAXIIVCTXAWGKA-UHFFFAOYSA-N FC(F)F.ClCCl Chemical compound FC(F)F.ClCCl SAXIIVCTXAWGKA-UHFFFAOYSA-N 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 1
- 102100032340 G2/mitotic-specific cyclin-B1 Human genes 0.000 description 1
- 102100033201 G2/mitotic-specific cyclin-B2 Human genes 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 208000031448 Genomic Instability Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000938346 Homo sapiens Ephrin type-A receptor 2 Proteins 0.000 description 1
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001504654 Mustela nivalis Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- MVDVWGITJFNBLD-UHFFFAOYSA-N N.B(O)O Chemical compound N.B(O)O MVDVWGITJFNBLD-UHFFFAOYSA-N 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- YKQCGIWMQBDJKY-UHFFFAOYSA-N P(=O)(O)(O)O.N1(C)C(=O)N(C)C=2N=CN(C)C2C1=O Chemical compound P(=O)(O)(O)O.N1(C)C(=O)N(C)C=2N=CN(C)C2C1=O YKQCGIWMQBDJKY-UHFFFAOYSA-N 0.000 description 1
- NHJSWORVNIOXIT-UHFFFAOYSA-N PD-166866 Chemical compound COC1=CC(OC)=CC(C=2C(=NC3=NC(N)=NC=C3C=2)NC(=O)NC(C)(C)C)=C1 NHJSWORVNIOXIT-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 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
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 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
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
- VKIJXFIYBAYHOE-VOTSOKGWSA-N [(e)-2-phenylethenyl]boronic acid Chemical compound OB(O)\C=C\C1=CC=CC=C1 VKIJXFIYBAYHOE-VOTSOKGWSA-N 0.000 description 1
- ZEABKUSEQKKPDM-UHFFFAOYSA-N [1-(2,4,6-trimethylphenyl)sulfonylpyrrol-2-yl]methanol Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)N1C(CO)=CC=C1 ZEABKUSEQKKPDM-UHFFFAOYSA-N 0.000 description 1
- VZWOXDYRBDIHMA-VMNATFBRSA-N [2H]C=1N=C(SC=1)C Chemical compound [2H]C=1N=C(SC=1)C VZWOXDYRBDIHMA-VMNATFBRSA-N 0.000 description 1
- IAATTYSEYPYMPK-UHFFFAOYSA-N [3-methoxy-4-(methoxymethoxy)phenyl]boronic acid Chemical compound COCOC1=CC=C(B(O)O)C=C1OC IAATTYSEYPYMPK-UHFFFAOYSA-N 0.000 description 1
- PIPAYWOJBHUHTA-UHFFFAOYSA-N [5-methoxy-2-methyl-4-(2-trimethylsilylethoxymethoxy)phenyl]boronic acid Chemical compound COC1=CC(B(O)O)=C(C)C=C1OCOCC[Si](C)(C)C PIPAYWOJBHUHTA-UHFFFAOYSA-N 0.000 description 1
- FRZHJLRHVBPCJQ-UHFFFAOYSA-N [I].[Na].[Na] Chemical compound [I].[Na].[Na] FRZHJLRHVBPCJQ-UHFFFAOYSA-N 0.000 description 1
- OUVUBOVVBOCNHV-UHFFFAOYSA-N [Li].FCC(=O)O Chemical compound [Li].FCC(=O)O OUVUBOVVBOCNHV-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- XKRFYHLGVUSROY-YPZZEJLDSA-N argon-38 Chemical compound [38Ar] XKRFYHLGVUSROY-YPZZEJLDSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 210000000941 bile Anatomy 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
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000005340 bisphosphate group Chemical group 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 244000309464 bull Species 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Chemical class 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 101150048033 cbh gene Proteins 0.000 description 1
- 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 1
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 150000001844 chromium Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 229960005537 combretastatin A-4 Drugs 0.000 description 1
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 229940126179 compound 72 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 235000019784 crude fat Nutrition 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 125000005534 decanoate group Chemical class 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 210000004513 dentition Anatomy 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- MKXZASYAUGDDCJ-QNNIAVNKSA-N deudextromethorphan Chemical compound C([C@@H]12)CCC[C@]11CCN(C([2H])([2H])[2H])[C@H]2CC2=CC=C(OC([2H])([2H])[2H])C=C21 MKXZASYAUGDDCJ-QNNIAVNKSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- FYDRKPQUPZTGEU-UHFFFAOYSA-N dichloromethane;ethene Chemical compound C=C.ClCCl FYDRKPQUPZTGEU-UHFFFAOYSA-N 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- IIGJYLXJNYBXEO-UHFFFAOYSA-N dimethoxymethanol Chemical compound COC(O)OC IIGJYLXJNYBXEO-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UBHZUDXTHNMNLD-UHFFFAOYSA-N dimethylsilane Chemical compound C[SiH2]C UBHZUDXTHNMNLD-UHFFFAOYSA-N 0.000 description 1
- ULAUBQTVYAVTFT-UHFFFAOYSA-N dinitro carbonate Chemical compound [O-][N+](=O)OC(=O)O[N+]([O-])=O ULAUBQTVYAVTFT-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002357 endometrial 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
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- MBTGWZLPWWAHCU-UHFFFAOYSA-N ethyl 2,3-difluorobenzoate Chemical compound CCOC(=O)C1=CC=CC(F)=C1F MBTGWZLPWWAHCU-UHFFFAOYSA-N 0.000 description 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
- JMGSSOAZZRYEAM-UHFFFAOYSA-N ethyl 3-fluoro-2-sulfanylbenzoate Chemical compound CCOC(=O)C1=CC=CC(F)=C1S JMGSSOAZZRYEAM-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 230000004116 glycogenolysis Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 150000002473 indoazoles Chemical class 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
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000302 ischemic effect 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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical class [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- QRPRIOOKPZSVFN-UHFFFAOYSA-M methyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 QRPRIOOKPZSVFN-UHFFFAOYSA-M 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- YNPFMWCWRVTGKJ-UHFFFAOYSA-N mianserin hydrochloride Chemical compound [H+].[Cl-].C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 YNPFMWCWRVTGKJ-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- XZYHDXZNNDZXSR-UHFFFAOYSA-N n-(1,1-dioxothiolan-3-yl)-n-methyl-2-[(4-phenyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)sulfanyl]acetamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C=2C=CC=CC=2)C=1SCC(=O)N(C)C1CCS(=O)(=O)C1 XZYHDXZNNDZXSR-UHFFFAOYSA-N 0.000 description 1
- OJWSNNNESCSTGB-UHFFFAOYSA-N n-(5-amino-2-fluorophenyl)benzamide Chemical compound NC1=CC=C(F)C(NC(=O)C=2C=CC=CC=2)=C1 OJWSNNNESCSTGB-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
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- WISBTQFQQVVPFL-UHFFFAOYSA-N n-bromo-n-methylmethanamine Chemical compound CN(C)Br WISBTQFQQVVPFL-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
- CPQCSJYYDADLCZ-UHFFFAOYSA-N n-methylhydroxylamine Chemical compound CNO CPQCSJYYDADLCZ-UHFFFAOYSA-N 0.000 description 1
- 125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CDZOGLJOFWFVOZ-UHFFFAOYSA-N n-propylaniline Chemical compound CCCNC1=CC=CC=C1 CDZOGLJOFWFVOZ-UHFFFAOYSA-N 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 239000003016 pheromone Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- UTVZCEMTWOZGFF-UHFFFAOYSA-L potassium tin(4+) carbonate Chemical compound C([O-])([O-])=O.[Sn+4].[K+] UTVZCEMTWOZGFF-UHFFFAOYSA-L 0.000 description 1
- OSIVISXRDMXJQR-UHFFFAOYSA-M potassium;2-[ethyl(1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctylsulfonyl)amino]acetate Chemical compound [K+].[O-]C(=O)CN(CC)S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F OSIVISXRDMXJQR-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- YGUNSCNKBIOMSG-UHFFFAOYSA-N propane-1-sulfinic acid Chemical compound CCCS(O)=O YGUNSCNKBIOMSG-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 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
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000009751 slip forming Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- UNHKSXOTUHOTAB-UHFFFAOYSA-N sodium;sulfane Chemical compound [Na].S UNHKSXOTUHOTAB-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- ZRRGOUHITGRLBA-UHFFFAOYSA-N stattic Chemical compound [O-][N+](=O)C1=CC=C2C=CS(=O)(=O)C2=C1 ZRRGOUHITGRLBA-UHFFFAOYSA-N 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960003288 sulfaethidole Drugs 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000005000 thioaryl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 230000036346 tooth eruption Effects 0.000 description 1
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 229960001124 trientine Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- PYGNJUGDXWJKII-UHFFFAOYSA-N trifluoromethylbenzene;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC=C1 PYGNJUGDXWJKII-UHFFFAOYSA-N 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 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
- 230000008728 vascular permeability Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14213099P | 1999-07-02 | 1999-07-02 | |
PCT/US2000/018263 WO2001002369A2 (en) | 1999-07-02 | 2000-06-30 | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
Publications (3)
Publication Number | Publication Date |
---|---|
HUP0202490A2 HUP0202490A2 (hu) | 2002-11-28 |
HUP0202490A3 HUP0202490A3 (en) | 2003-01-28 |
HU228502B1 true HU228502B1 (en) | 2013-03-28 |
Family
ID=22498654
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU0202490A HU228502B1 (en) | 1999-07-02 | 2000-06-30 | Indazole derivatives and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
Country Status (52)
Families Citing this family (334)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CZ306810B6 (cs) | 1999-02-10 | 2017-07-19 | Astrazeneca Ab | Použití chinazolinového derivátu jako inhibitoru angiogeneze |
PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
EA005212B1 (ru) | 1999-12-24 | 2004-12-30 | Авентис Фарма Лимитед | Азаиндолы |
CA2399274A1 (en) | 2000-02-07 | 2001-08-09 | Mark E. Salvati | 3-aminopyrazole inhibitors of cyclin dependent kinases |
US20040087798A1 (en) * | 2000-03-14 | 2004-05-06 | Akira Yamada | Novel amide compounds |
ES2236217T3 (es) | 2000-04-25 | 2005-07-16 | Bristol-Myers Squibb Company | Uso de 5.tio.,sulfinil- y sulfonilpirazolo 3,4-b)-piridinas como inhibidores de la quinasa dependiente de la ciclina. |
US6887874B2 (en) | 2000-08-09 | 2005-05-03 | Astrazeneca Ab | Cinnoline compounds |
BR0113056A (pt) | 2000-08-09 | 2003-07-08 | Astrazeneca Ab | Composto, processo papa a preparação do mesmo, composição farmacêutica, e, método para produzir um efeito antiangiogênico e/ou redutor da permeabilidade vascular em um animal de sangue quente, e, uso de um composto |
US6756383B2 (en) | 2000-09-01 | 2004-06-29 | Chiron Corporation | Heterocyclic derivatives of quinolinone benimidazoles |
CZ304344B6 (cs) | 2000-09-11 | 2014-03-19 | Novartis Vaccines & Diagnostics, Inc. | Chinolinonový derivát a jeho použití a farmaceutický prostředek s obsahem tohoto derivátu |
ATE399766T1 (de) | 2000-10-20 | 2008-07-15 | Eisai R&D Man Co Ltd | Stickstoff enthaltende aromatische heterozyklen |
TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
US7642278B2 (en) | 2001-07-03 | 2010-01-05 | Novartis Vaccines And Diagnostics, Inc. | Indazole benzimidazole compounds |
US7064215B2 (en) | 2001-07-03 | 2006-06-20 | Chiron Corporation | Indazole benzimidazole compounds |
US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6897208B2 (en) * | 2001-10-26 | 2005-05-24 | Aventis Pharmaceuticals Inc. | Benzimidazoles |
FR2831537B1 (fr) * | 2001-10-26 | 2008-02-29 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation |
FR2831536A1 (fr) * | 2001-10-26 | 2003-05-02 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de kdr |
WO2003035065A1 (en) * | 2001-10-26 | 2003-05-01 | Aventis Pharmaceuticals Inc | Benzimidazoles and analogues and their use as protein kinases inhibitors |
KR101093345B1 (ko) | 2002-02-01 | 2011-12-14 | 아스트라제네카 아베 | 퀴나졸린 화합물 |
US7166293B2 (en) | 2002-03-29 | 2007-01-23 | Carlsbad Technology, Inc. | Angiogenesis inhibitors |
US20050119278A1 (en) * | 2002-05-16 | 2005-06-02 | Che-Ming Teng | Anti-angiogenesis methods |
US7186716B2 (en) | 2002-08-12 | 2007-03-06 | Sugen, Inc. | 3-Pyrrol-pyridopyrazoles and 3-pyrrolyl-indazoles as novel kinase inhibitors |
EP1539754A4 (en) | 2002-08-23 | 2009-02-25 | Novartis Vaccines & Diagnostic | BENZIMIDAZOLE QUINOLINONES AND USES THEREOF |
WO2004050088A1 (ja) * | 2002-12-03 | 2004-06-17 | Kyowa Hakko Kogyo Co., Ltd. | Jnk阻害剤 |
CA2510850A1 (en) * | 2002-12-19 | 2004-07-08 | Pfizer Inc. | 2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophthalmic diseases |
US7192976B2 (en) | 2002-12-21 | 2007-03-20 | Angion Biomedica Corporation | Small molecule modulators of hepatocyte growth factor (scatter factor) activity |
US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
WO2004078116A2 (en) | 2003-03-03 | 2004-09-16 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
CA2520932A1 (en) * | 2003-04-03 | 2004-10-14 | Pfizer Inc. | Dosage forms comprising ag013736 |
EP1618133A1 (en) * | 2003-04-17 | 2006-01-25 | Pfizer Inc. | Crystal structure of vegfrkd: ligand complexes and methods of use thereof |
FR2854159B1 (fr) * | 2003-04-25 | 2008-01-11 | Aventis Pharma Sa | Nouveaux derives de l'indole, leur preparation a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de kdr |
TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
EP1651612B9 (en) | 2003-07-22 | 2012-09-05 | Astex Therapeutics Limited | 3,4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
AU2004259012C1 (en) * | 2003-07-23 | 2012-08-02 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
EP1652842B1 (en) * | 2003-07-30 | 2012-04-11 | Kyowa Hakko Kirin Co., Ltd. | Indazole derivatives |
WO2005012258A1 (ja) * | 2003-07-30 | 2005-02-10 | Kyowa Hakko Kogyo Co., Ltd. | タンパク質キナーゼ阻害剤 |
JP2007504236A (ja) * | 2003-09-04 | 2007-03-01 | メルク エンド カムパニー インコーポレーテッド | 高眼圧症を治療するための眼用組成物 |
WO2005028624A2 (en) * | 2003-09-15 | 2005-03-31 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
WO2005039564A1 (en) * | 2003-10-02 | 2005-05-06 | Vertex Pharmaceuticals Incorporated | Phthalimide compounds useful as protein kinase inhibitors |
AU2004288709B2 (en) | 2003-11-07 | 2011-01-06 | Novartis Vaccines And Diagnostics, Inc. | Methods for synthesizing quinolinone compounds |
US7683172B2 (en) | 2003-11-11 | 2010-03-23 | Eisai R&D Management Co., Ltd. | Urea derivative and process for preparing the same |
JP2007511618A (ja) * | 2003-11-19 | 2007-05-10 | シグナル ファーマシューティカルズ,エルエルシー | インダゾール化合物およびタンパク質キナーゼ阻害剤としてのその使用方法 |
GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
EP1747202A1 (en) * | 2004-02-27 | 2007-01-31 | F.Hoffmann-La Roche Ag | Indazole derivatives and pharmaceutical compositions containing them |
EP1720855A4 (en) * | 2004-03-02 | 2008-12-17 | Smithkline Beecham Corp | HEMMER OF ACT ACTIVITY |
WO2005094823A1 (ja) * | 2004-03-30 | 2005-10-13 | Kyowa Hakko Kogyo Co., Ltd. | Flt-3阻害剤 |
WO2005108370A1 (ja) * | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | ベンゼン化合物 |
JP2008503446A (ja) | 2004-05-06 | 2008-02-07 | プレキシコン,インコーポレーテッド | Pde4b阻害剤及びその使用 |
CN1968948A (zh) | 2004-06-17 | 2007-05-23 | 惠氏公司 | 用于制备促性腺激素释放激素受体拮抗剂的方法 |
CN101006078A (zh) * | 2004-06-17 | 2007-07-25 | 惠氏公司 | 促性腺素释放激素受体拮抗剂 |
MX2007001986A (es) * | 2004-08-26 | 2007-05-10 | Pfizer | Compuestos de aminoheteroarilo como inhibidores de proteina quinasa. |
JP2008512380A (ja) | 2004-09-03 | 2008-04-24 | プレキシコン,インコーポレーテッド | Pde4b阻害剤 |
KR20070053205A (ko) | 2004-09-17 | 2007-05-23 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 의약 조성물 |
EP1647549A1 (en) * | 2004-10-14 | 2006-04-19 | Laboratoire Theramex | Indazoles, benzisoxazoles and benzisothiazoles as estrogenic agents |
CA2586177A1 (en) * | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Polymorphic forms of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-e-[2-(pyridin-2-yl)ethenyl]indazole |
AU2005300311A1 (en) * | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for preparing indazole compounds |
CA2591313A1 (en) * | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for preparing indazole compounds |
US9512125B2 (en) | 2004-11-19 | 2016-12-06 | The Regents Of The University Of California | Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents |
FR2878442B1 (fr) * | 2004-11-29 | 2008-10-24 | Aventis Pharma Sa | THIENO(2,3-c)PYRAZOLES SUBSTITUES, PROCEDE DE PREPARATION, COMPOSITIONS LES CONTENANT ET UTILISATION |
US20060142247A1 (en) * | 2004-12-17 | 2006-06-29 | Guy Georges | Tricyclic heterocycles |
TWI427077B (zh) | 2004-12-30 | 2014-02-21 | Astex Therapeutics Ltd | 吡唑化合物及其用途和含有彼之藥學組成物 |
US7622583B2 (en) | 2005-01-14 | 2009-11-24 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
MX2007008810A (es) | 2005-01-21 | 2007-11-21 | Astex Therapeutics Ltd | Compuestos farmaceuticos. |
WO2006077428A1 (en) | 2005-01-21 | 2006-07-27 | Astex Therapeutics Limited | Pharmaceutical compounds |
WO2006081230A2 (en) * | 2005-01-26 | 2006-08-03 | Schering Corporation | 3-(indazol-5-yl)-(1,2, 4) triazine derivatives and related compounds as protein kinase inhibitors for the treatment of cancer |
KR20070108881A (ko) | 2005-01-27 | 2007-11-13 | 교와 핫꼬 고교 가부시끼가이샤 | Igf-1r 저해제 |
US7538113B2 (en) | 2005-02-18 | 2009-05-26 | Wyeth | 4-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
US7582634B2 (en) | 2005-02-18 | 2009-09-01 | Wyeth | 7-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
US7534796B2 (en) | 2005-02-18 | 2009-05-19 | Wyeth | Imidazo[4,5-b]pyridine antagonists of gonadotropin releasing hormone receptor |
PL1888556T3 (pl) | 2005-05-17 | 2012-03-30 | Novartis Ag | Metody syntetyzowania związków heterocyklicznych |
US7531542B2 (en) | 2005-05-18 | 2009-05-12 | Wyeth | Benzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor |
EP1885338A1 (en) * | 2005-05-19 | 2008-02-13 | Pfizer, Inc. | Pharmaceutical compostions comprising an amorphous form of a vegf-r inhibitor |
EP2354139A1 (en) * | 2005-05-20 | 2011-08-10 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
US7582636B2 (en) | 2005-05-26 | 2009-09-01 | Wyeth | Piperazinylimidazopyridine and piperazinyltriazolopyridine antagonists of Gonadotropin Releasing Hormone receptor |
US7541367B2 (en) | 2005-05-31 | 2009-06-02 | Janssen Pharmaceutica, N.V. | 3-benzoimidazolyl-pyrazolopyridines useful in treating kinase disorders |
US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
EP1925676A4 (en) | 2005-08-02 | 2010-11-10 | Eisai R&D Man Co Ltd | TEST METHOD FOR THE EFFECT OF A VASCULARIZATION INHIBITOR |
MY148529A (en) | 2005-11-29 | 2013-04-30 | Novartis Ag | Formulations of quinolinones |
TW200732305A (en) * | 2005-12-23 | 2007-09-01 | Yung Shin Pharmaceutical Ind | Cancer chemotherapy |
CA2635813C (en) | 2006-01-31 | 2014-01-07 | Array Biopharma, Inc. | Urea derivatives as kinase inhibitors and methods of use thereof |
BRPI0709082A2 (pt) * | 2006-03-23 | 2011-06-28 | Hoffmann La Roche | derivados de indazol substituìdos, sua fabricação e uso como agentes farmacêuticos |
US20080032960A1 (en) | 2006-04-04 | 2008-02-07 | Regents Of The University Of California | PI3 kinase antagonists |
EP2036557B1 (en) | 2006-05-18 | 2015-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for thyroid cancer |
JPWO2008001885A1 (ja) | 2006-06-30 | 2009-11-26 | 協和発酵キリン株式会社 | Ablキナーゼ阻害剤 |
EP2036894A4 (en) | 2006-06-30 | 2011-01-12 | Kyowa Hakko Kirin Co Ltd | AURORA INHIBITOR |
US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
WO2008020606A1 (fr) * | 2006-08-16 | 2008-02-21 | Kyowa Hakko Kirin Co., Ltd. | Agent anti-angiogénique |
WO2008026748A1 (fr) | 2006-08-28 | 2008-03-06 | Eisai R & D Management Co., Ltd. | Agent antitumoral pour cancer gastrique non différencié |
CL2007002617A1 (es) | 2006-09-11 | 2008-05-16 | Sanofi Aventis | Compuestos derivados de pirrolo[2,3-b]pirazin-6-ilo; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar inflamacion de las articulaciones, artritis reumatoide, tumores, linfoma de las celulas del manto. |
US8962655B2 (en) | 2007-01-29 | 2015-02-24 | Eisai R&D Management Co., Ltd. | Composition for treatment of undifferentiated gastric cancer |
TW200901975A (en) | 2007-03-05 | 2009-01-16 | Kyowa Hakko Kogyo Kk | Pharmaceutical composition |
CN103087043A (zh) * | 2007-03-16 | 2013-05-08 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 具有抗增殖活性的苯甲酰胺类衍生物及其药用制剂 |
EP3252047B1 (en) * | 2007-04-05 | 2022-05-11 | Pfizer Products Inc. | Crystalline forms of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-e-[2-(pyridin-2-yl)ethenyl]indazole suitable for the treatment of abnormal cell growth in mammals |
EP2002836B1 (en) | 2007-05-31 | 2010-10-20 | Nerviano Medical Sciences S.r.l. | Cyclocondensed azaindoles active as kinase inhibitors |
CA2692761C (en) | 2007-07-12 | 2013-04-30 | Chemocentryx, Inc. | Fused heteroaryl pyridyl and phenyl benzenesulfonamides as ccr2 modulators for the treament of inflammation |
WO2009046448A1 (en) | 2007-10-04 | 2009-04-09 | Intellikine, Inc. | Chemical entities and therapeutic uses thereof |
EP2212290B1 (en) * | 2007-10-11 | 2014-12-03 | Vertex Pharmaceuticals Incorporated | Aryl amides useful as inhibitors of voltage-gated sodium channels |
KR20100093552A (ko) | 2007-11-02 | 2010-08-25 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제 c-세타로서의 [1h-피라졸로[3,4-b]피리딘-4-일]-페닐 또는 -피리딘-2-일 유도체 |
AU2008325608B2 (en) | 2007-11-09 | 2013-03-14 | Eisai R & D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
NZ613219A (en) | 2008-01-04 | 2014-11-28 | Intellikine Llc | Heterocyclic containing entities, compositions and methods |
WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
JP5547099B2 (ja) | 2008-03-14 | 2014-07-09 | インテリカイン, エルエルシー | キナーゼ阻害剤および使用方法 |
CA2722102C (en) | 2008-04-28 | 2013-06-11 | Asahi Kasei Pharma Corporation | Phenylpropionic acid derivative and use thereof |
CN102124009B (zh) | 2008-07-08 | 2014-07-23 | 因特利凯公司 | 激酶抑制剂及其使用方法 |
US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
CN102149379A (zh) | 2008-07-10 | 2011-08-10 | 安吉翁生物医药有限公司 | 调节肝细胞生长因子(分散因子)活性的方法和肝细胞生长因子(分散因子)活性的小分子调节剂组合物 |
WO2010036380A1 (en) | 2008-09-26 | 2010-04-01 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
AU2009305669A1 (en) | 2008-10-16 | 2010-04-22 | The Regents Of The University Of California | Fused ring heteroaryl kinase inhibitors |
US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
CN104030987B (zh) | 2009-04-02 | 2017-04-12 | 默克雪兰诺有限公司 | 二氢乳清酸脱氢酶抑制剂 |
EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
EP2987487B1 (en) | 2009-08-10 | 2020-10-07 | Samumed, LLC | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
US8980899B2 (en) | 2009-10-16 | 2015-03-17 | The Regents Of The University Of California | Methods of inhibiting Ire1 |
WO2011073521A1 (en) | 2009-12-15 | 2011-06-23 | Petri Salven | Methods for enriching adult-derived endothelial progenitor cells and uses thereof |
CN102821607B (zh) | 2009-12-21 | 2014-12-17 | 萨穆梅德有限公司 | 1H-吡唑并[3,4-b]吡啶及其治疗应用 |
EP2519517B1 (en) | 2009-12-29 | 2015-03-25 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
UY33236A (es) | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
BR112012023021A2 (pt) * | 2010-03-16 | 2016-05-31 | Dana Farber Cancer Inst Inc | compostos de indazol e seus usos |
ES2593256T3 (es) | 2010-05-21 | 2016-12-07 | Infinity Pharmaceuticals, Inc. | Compuestos químicos, composiciones y métodos para las modulaciones de cinasas |
ES2573515T3 (es) | 2010-06-25 | 2016-06-08 | Eisai R&D Management Co., Ltd. | Agente antitumoral que emplea compuestos con efecto inhibitorio de cinasas combinados |
JP2013538191A (ja) | 2010-07-23 | 2013-10-10 | トラスティーズ オブ ボストン ユニバーシティ | 病的血管新生および腫瘍細胞侵襲性の阻害のための治療法としてならびに分子イメージングおよび標的化送達のための抗DEsupR阻害剤 |
CA2817577A1 (en) | 2010-11-10 | 2012-05-18 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
US20130266590A1 (en) | 2010-12-13 | 2013-10-10 | Novartis Ag | Dimeric iap inhibitors |
US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
UA115767C2 (uk) | 2011-01-10 | 2017-12-26 | Інфініті Фармасьютікалз, Інк. | Способи отримання ізохінолінонів і тверді форми ізохінолінонів |
CN106619647A (zh) | 2011-02-23 | 2017-05-10 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
EP2694060A4 (en) | 2011-04-01 | 2014-09-10 | Univ Utah Res Found | SUBSTITUTED 3- (1H-BENZO [D] IMIDAZOL-2-YL) -1H-INDAZOLE ANALOGUES AS INHIBITORS OF PDK1 KINASE |
RU2580609C2 (ru) | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
ES2705950T3 (es) | 2011-06-03 | 2019-03-27 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y valorar la capacidad de respuesta de sujetos con cáncer de tiroides y de riñón a compuestos de lenvatinib |
US8969363B2 (en) | 2011-07-19 | 2015-03-03 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
US9056877B2 (en) | 2011-07-19 | 2015-06-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
US8575336B2 (en) | 2011-07-27 | 2013-11-05 | Pfizer Limited | Indazoles |
PE20141371A1 (es) | 2011-08-29 | 2014-10-13 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
EP2751112B1 (en) | 2011-09-02 | 2019-10-09 | The Regents of The University of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
CN102432595B (zh) * | 2011-09-14 | 2013-09-25 | 湖南有色凯铂生物药业有限公司 | N-吲哚-1-酰胺类化合物及作为抗癌药物的应用 |
HUE041576T2 (hu) | 2011-09-14 | 2019-05-28 | Samumed Llc | Indazol-3-karboxamid-származékok és alkalmazásuk Wnt/b-katenin szignalizáló útvonal inhibitorokként |
EP2771337B1 (en) | 2011-09-27 | 2017-08-02 | Novartis AG | 3-(pyrimidin-4-yl)-oxazolidin-2-ones as inhibitors of mutant idh |
JP6106685B2 (ja) | 2011-11-17 | 2017-04-05 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | C−jun−n−末端キナーゼ(jnk)の阻害剤 |
AU2012349726A1 (en) | 2011-12-05 | 2014-06-26 | Novartis Ag | Cyclic urea derivatives as androgen receptor antagonists |
FR2985257B1 (fr) * | 2011-12-28 | 2014-02-14 | Sanofi Sa | Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique |
WO2013105022A2 (en) | 2012-01-09 | 2013-07-18 | Novartis Ag | Organic compositions to treat beta-catenin-related diseases |
JO3357B1 (ar) | 2012-01-26 | 2019-03-13 | Novartis Ag | مركبات إيميدازوبيروليدينون |
PH12017500997A1 (en) | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
DK2770994T3 (da) | 2012-05-04 | 2019-11-11 | Samumed Llc | 1h-pyrazolo[3,4-b]pyridiner og terapeutiske anvendelser deraf |
ME03300B (me) | 2012-06-13 | 2019-07-20 | Incyte Holdings Corp | Supsтituisana triciklična jedinjenja као inhibiтori fgfr |
JP6231262B2 (ja) * | 2012-06-20 | 2017-11-15 | 大日本印刷株式会社 | ピタバスタチンカルシウムの前駆体の製造法 |
US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
JP2015532287A (ja) | 2012-09-26 | 2015-11-09 | ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア | Ire1の調節 |
WO2014063068A1 (en) | 2012-10-18 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2014063061A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
WO2014063054A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Bone marrow on x chromosome kinase (bmx) inhibitors and uses thereof |
CN103804349A (zh) * | 2012-11-01 | 2014-05-21 | 杨子娇 | 一类治疗青光眼的化合物及其用途 |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
EP2937337A4 (en) | 2012-12-21 | 2016-06-22 | Eisai R&D Man Co Ltd | AMORPHIC FORM OF CHINOLINE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF |
CA2897400A1 (en) | 2013-01-08 | 2014-07-17 | Samumed, Llc | 3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof |
CN104370889A (zh) * | 2013-01-24 | 2015-02-25 | 韩冰 | 一类降低眼压的化合物及其制备方法和用途 |
US9708295B2 (en) * | 2013-02-02 | 2017-07-18 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Substituted 2-aminopyridine protein kinase inhibitor |
WO2014130310A1 (en) | 2013-02-19 | 2014-08-28 | Novartis Ag | Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders |
JP2016514124A (ja) | 2013-03-14 | 2016-05-19 | ノバルティス アーゲー | 変異idhの阻害薬としての3−ピリミジン−4−イル−オキサゾリジン−2−オン |
CA2903979A1 (en) | 2013-03-14 | 2014-09-18 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
WO2014147586A1 (en) | 2013-03-22 | 2014-09-25 | Novartis Ag | 1-(2-(ethylamino)pyrimidin-4-yl)pyrrolidin-2-ones as inhibitors of mutant idh |
ES2657451T3 (es) | 2013-04-19 | 2018-03-05 | Incyte Holdings Corporation | Heterocíclicos bicíclicos como inhibidores del FGFR |
NZ714049A (en) | 2013-05-14 | 2020-05-29 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
US20150018376A1 (en) * | 2013-05-17 | 2015-01-15 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
CN103387565B (zh) * | 2013-07-29 | 2014-10-29 | 苏州明锐医药科技有限公司 | 阿西替尼的制备方法 |
WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
EA201690713A1 (ru) | 2013-10-04 | 2016-08-31 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения и их применения |
EP3057956B1 (en) | 2013-10-18 | 2021-05-05 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2015058126A1 (en) | 2013-10-18 | 2015-04-23 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
CN103570696B (zh) * | 2013-11-06 | 2016-02-24 | 湖南欧亚生物有限公司 | 一种阿西替尼中间体的制备方法以及在制备阿西替尼中的应用 |
WO2015067224A1 (en) | 2013-11-08 | 2015-05-14 | Zentiva, K.S. | Salts of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-e-[2-(pyridin-2-yl)ethanyl] indazole |
WO2015092634A1 (en) | 2013-12-16 | 2015-06-25 | Novartis Ag | 1,2,3,4-tetrahydroisoquinoline compounds and compositions as selective estrogen receptor antagonists and degraders |
JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
CN105899493B (zh) | 2014-01-17 | 2019-03-29 | 诺华股份有限公司 | 用于抑制shp2活性的1-(三嗪-3-基/哒嗪-3-基)-哌(-嗪)啶衍生物及其组合物 |
US10093646B2 (en) | 2014-01-17 | 2018-10-09 | Novartis Ag | 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2 |
DK3119397T3 (da) | 2014-03-19 | 2022-03-28 | Infinity Pharmaceuticals Inc | Heterocykliske forbindelser til anvendelse i behandling af PI3K-gamma-medierede lidelser |
EP3127900B1 (en) * | 2014-03-31 | 2017-10-18 | Senju Pharmaceutical Co., Ltd. | Alkynyl indazole derivative and use thereof |
WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
US10017477B2 (en) | 2014-04-23 | 2018-07-10 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
US9862688B2 (en) | 2014-04-23 | 2018-01-09 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
WO2015181624A2 (en) | 2014-05-28 | 2015-12-03 | Idenix Pharmaceuticals, Inc | Nucleoside derivatives for the treatment of cancer |
CN104072484B (zh) * | 2014-07-07 | 2016-07-06 | 渤海大学 | 氮-(4-(芳巯基)-1氢-吲唑-3-基)-1-(芳杂环取代)甲基亚胺类化合物及其药学上可接受的盐及其制备方法和应用 |
AR101196A1 (es) | 2014-07-16 | 2016-11-30 | Gruenenthal Gmbh | Compuestos de pirimidina sustituidos |
AR101198A1 (es) | 2014-07-16 | 2016-11-30 | Gruenenthal Gmbh | Pirimidinas 2,5-sustituidas como inhibidores de pde4b |
TWI721954B (zh) | 2014-08-28 | 2021-03-21 | 日商衛材R&D企管股份有限公司 | 高純度喹啉衍生物及其生產方法 |
WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040193A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040180A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040188A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040182A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof |
BR112017005510A2 (pt) | 2014-09-17 | 2018-08-14 | Celgene Quanticel Res Inc | inibidores da histona-desmetilase. |
US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
US10086000B2 (en) | 2014-12-05 | 2018-10-02 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
EP3226689B1 (en) | 2014-12-05 | 2020-01-15 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
WO2016089797A1 (en) | 2014-12-05 | 2016-06-09 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
MA41140A (fr) | 2014-12-12 | 2017-10-17 | Cancer Research Tech Ltd | Dérivés de 2,4-dioxo-quinazoline-6-sulfonamide en tant qu'inhibiteurs de la parg |
MA41179A (fr) * | 2014-12-19 | 2017-10-24 | Cancer Research Tech Ltd | Composés inhibiteurs de parg |
US10870651B2 (en) | 2014-12-23 | 2020-12-22 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
EP3789027A1 (en) | 2015-01-13 | 2021-03-10 | Kyoto University | Bosutinib, sunitinib, tivozanib, imatinib, nilotinib, rebastinib or bafetinib for preventing and/or treating amyotrophic lateral sclerosis |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
ES2751669T3 (es) | 2015-02-20 | 2020-04-01 | Incyte Corp | Heterociclos bicíclicos como inhibidores FGFR |
US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
RU2017128583A (ru) | 2015-02-25 | 2019-03-25 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Способ ослабления горечи хинолинового производного |
CA2978226A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharpe & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
JP6861166B2 (ja) | 2015-03-27 | 2021-04-21 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
US9580406B2 (en) | 2015-04-28 | 2017-02-28 | Signa S.A. De C.V. | Processes for the preparation of axitinib |
EP3303361A1 (en) | 2015-05-27 | 2018-04-11 | Idenix Pharmaceuticals LLC | Nucleotides for the treatment of cancer |
EP3307728A4 (en) | 2015-06-12 | 2019-07-17 | Dana Farber Cancer Institute, Inc. | ASSOCIATION THERAPY USING TRANSCRIPTION INHIBITORS AND KINASE INHIBITORS |
AU2016279474B2 (en) | 2015-06-16 | 2021-09-09 | Eisai R&D Management Co., Ltd. | Anticancer agent |
EP3310774B1 (en) | 2015-06-19 | 2020-04-29 | Novartis AG | Compounds and compositions for inhibiting the activity of shp2 |
EP3310771B1 (en) | 2015-06-19 | 2020-07-22 | Novartis AG | Compounds and compositions for inhibiting the activity of shp2 |
ES2741746T3 (es) | 2015-06-19 | 2020-02-12 | Novartis Ag | Compuestos y composiciones para inhibir la actividad de SHP2 |
GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
GB201511790D0 (en) | 2015-07-06 | 2015-08-19 | Iomet Pharma Ltd | Pharmaceutical compound |
WO2017024021A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
WO2017023984A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10206909B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017023972A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10226448B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-yl)-1H-pyrazolo[3,4-B]pyridines and therapeutic uses thereof |
WO2017024010A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
WO2017023988A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
WO2017024015A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10604512B2 (en) | 2015-08-03 | 2020-03-31 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-indazoles and therapeutic uses thereof |
WO2017024025A1 (en) | 2015-08-03 | 2017-02-09 | Sunil Kumar Kc | 3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
WO2017023996A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
US10392383B2 (en) | 2015-08-03 | 2019-08-27 | Samumed, Llc | 3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
WO2017023975A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
WO2017024003A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10285982B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
WO2017023993A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-indol-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10166218B2 (en) | 2015-08-03 | 2019-01-01 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
EP3334745B1 (en) | 2015-08-13 | 2024-05-15 | Merck Sharp & Dohme LLC | Cyclic di-nucleotide compounds as sting agonists |
JP7028766B2 (ja) | 2015-09-09 | 2022-03-02 | ダナ-ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
AU2016322552B2 (en) | 2015-09-14 | 2021-03-25 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
KR102317700B1 (ko) * | 2015-10-07 | 2021-10-26 | 아이비바 바이오파마, 인크. | 피부 섬유성 장애를 치료하는 조성물 및 방법 |
MX2018004879A (es) * | 2015-10-22 | 2019-02-28 | Selvita S A | Nuevos derivados de piridona y su uso como inhibidores de quinasas. |
CN108472290A (zh) | 2015-11-06 | 2018-08-31 | 萨穆梅德有限公司 | 治疗骨关节炎 |
EP3389783A4 (en) | 2015-12-15 | 2019-05-15 | Merck Sharp & Dohme Corp. | NOVEL COMPOUNDS THAN INDOLAMINE-2,3-DIOXYGENASE INHIBITORS |
WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
CA3023032A1 (en) | 2016-05-04 | 2017-11-09 | Genoscience Pharma | Substituted 2,4-diamino-quinoline derivatives for use in the treatment of proliferative diseases |
SG11201810683VA (en) | 2016-06-01 | 2018-12-28 | Samumed Llc | Process for preparing n-(5-(3-(7-(3-fluorophenyl)-3h-imidazo[4,5-c]pyridin-2-yl)-1h-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide |
WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2017216706A1 (en) | 2016-06-14 | 2017-12-21 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
KR20190033526A (ko) | 2016-06-24 | 2019-03-29 | 인피니티 파마슈티칼스, 인코포레이티드 | 병용 요법 |
CR20190168A (es) | 2016-10-04 | 2019-05-17 | Merck Sharp & Dohme | Compuestos de benzo[b]tiofeno como agonistas de sting |
MX2019004616A (es) | 2016-10-21 | 2019-11-21 | Samumed Llc | Métodos de uso de indazol-3-carboxamidas y su uso como inhibidores de la ruta de señalización de wnt/b-catenina. |
WO2018085865A1 (en) | 2016-11-07 | 2018-05-11 | Samumed, Llc | Single-dose, ready-to-use injectable formulations |
WO2018091542A1 (en) | 2016-11-21 | 2018-05-24 | Idenix Pharmaceuticals Llc | Cyclic phosphate substituted nucleoside derivatives for the treatment of liver diseases |
RU2765737C2 (ru) | 2016-11-23 | 2022-02-02 | Хемоцентрикс, Инк. | Способ лечения фокально-сегментарного гломерулосклероза |
ES2891326T3 (es) | 2017-01-27 | 2022-01-27 | Janssen Biotech Inc | Dinucleótidos cíclicos como agonistas de la STING |
AU2018212788A1 (en) | 2017-01-27 | 2019-07-25 | Janssen Biotech, Inc. | Cyclic dinucleotides as STING agonists |
JP6803410B2 (ja) | 2017-02-14 | 2020-12-23 | 富士フイルム株式会社 | インダゾール化合物の製造方法およびインダゾール化合物 |
EP3621624B1 (en) | 2017-05-12 | 2023-08-30 | Merck Sharp & Dohme LLC | Cyclic di-nucleotide compounds as sting agonists |
CN108947970B (zh) * | 2017-05-18 | 2022-04-05 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
US11285131B2 (en) | 2017-08-04 | 2022-03-29 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene STING agonists for cancer treatment |
AU2018311965A1 (en) | 2017-08-04 | 2020-02-13 | Merck Sharp & Dohme Llc | Combinations of PD-1 antagonists and benzo[b]thiophene sting antagonists for cancer treatment |
WO2019038412A1 (en) | 2017-08-24 | 2019-02-28 | Novo Nordisk A/S | GLP-1 COMPOSITIONS AND USES THEREOF |
US10435389B2 (en) | 2017-09-11 | 2019-10-08 | Krouzon Pharmaccuticals, Inc. | Octahydrocyclopenta[c]pyrrole allosteric inhibitors of SHP2 |
WO2019067332A1 (en) | 2017-09-27 | 2019-04-04 | Merck Sharp & Dohme Corp. | COMPOSITIONS AND METHODS FOR TREATING CANCER THROUGH A COMBINATION OF PROGRAMMED DEATH ANTIBODY ANTIBODIES (PD-1) AND A CXCR2 ANTAGONIST |
BR112020007183A2 (pt) | 2017-10-11 | 2020-09-24 | Chemocentryx, Inc. | tratamento de glomeruloesclerose focal segmentado com antagonistas de ccr2 |
WO2019089412A1 (en) | 2017-11-01 | 2019-05-09 | Merck Sharp & Dohme Corp. | Novel substituted tetrahydroquinolin compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
US10647705B2 (en) | 2017-11-14 | 2020-05-12 | Merck Sharp & Dohme Corp. | Substituted biaryl compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors |
US11498904B2 (en) | 2017-11-14 | 2022-11-15 | Merck Sharp & Dohme Llc | Substituted biaryl compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors |
WO2019125974A1 (en) | 2017-12-20 | 2019-06-27 | Merck Sharp & Dohme Corp. | Cyclic di-nucleotide compounds as sting agonists |
BR112020020085A8 (pt) | 2018-04-03 | 2023-04-11 | Merck Sharp & Dohme | Composto, composição farmacêutica, e, métodos para induzir uma resposta imune, para induzir produção de interferons de tipo i dependentes de sting e para tratar um distúrbio de proliferação celular |
US11702430B2 (en) | 2018-04-03 | 2023-07-18 | Merck Sharp & Dohme Llc | Aza-benzothiophene compounds as STING agonists |
JP2021523118A (ja) | 2018-05-04 | 2021-09-02 | インサイト・コーポレイションIncyte Corporation | Fgfr阻害剤の塩 |
CR20200590A (es) | 2018-05-04 | 2021-04-26 | Incyte Corp | Formas sólidas de un inhibidor de fgfr y procesos para prepararlas |
CN110452176A (zh) * | 2018-05-07 | 2019-11-15 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
WO2019231870A1 (en) | 2018-05-31 | 2019-12-05 | Merck Sharp & Dohme Corp. | Novel substituted [1.1.1] bicyclo compounds as indoleamine 2,3-dioxygenase inhibitors |
CA3113234A1 (en) | 2018-09-18 | 2020-03-26 | Nikang Therapeutics, Inc. | Tri-substituted heteroaryl derivatives as src homology-2 phosphatase inhibitors |
CN113164776A (zh) | 2018-09-25 | 2021-07-23 | 黑钻治疗公司 | 酪氨酸激酶抑制剂组合物、其制备方法和使用方法 |
AU2019346550A1 (en) | 2018-09-25 | 2021-04-22 | Black Diamond Therapeutics, Inc. | Quinazoline derivatives as tyrosine kinase inhibitor, compositions, methods of making them and their use |
EP4282416A3 (en) | 2018-09-29 | 2024-03-06 | Novartis AG | Process of manufacture of a compound for inhibiting the activity of shp2 |
WO2020092183A1 (en) | 2018-11-01 | 2020-05-07 | Merck Sharp & Dohme Corp. | Novel substituted pyrazole compounds as indoleamine 2,3-dioxygenase inhibitors |
WO2020096871A1 (en) | 2018-11-06 | 2020-05-14 | Merck Sharp & Dohme Corp. | Novel substituted tricyclic compounds as indoleamine 2,3-dioxygenase inhibitors |
CN111205227A (zh) * | 2018-11-22 | 2020-05-29 | 四川大学 | 3-乙烯基吲唑类衍生物及其制备方法和用途 |
EP3886845A4 (en) | 2018-11-28 | 2022-08-10 | Merck Sharp & Dohme Corp. | NEW SUBSTITUTED PIPERAZINE AMIDE COMPOUNDS USED AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS |
WO2020160151A1 (en) * | 2019-01-31 | 2020-08-06 | Kyorin Pharmaceutical Co., Ltd. | 15-pgdh inhibitors |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
EP3946324A4 (en) | 2019-04-04 | 2022-11-30 | Merck Sharp & Dohme LLC | HISTONE DEACETYLASE-3 INHIBITORS USEFUL FOR THE TREATMENT OF CANCER, INFLAMMATION, NEURODEGENERATIVE DISEASES AND DIABETES |
KR20220004083A (ko) | 2019-04-11 | 2022-01-11 | 앤지온 바이오메디카 코포레이션 | (e)-3-[2-(2-티에닐)비닐]-1h-피라졸의 고체 형태 |
US20220194921A1 (en) | 2019-04-18 | 2022-06-23 | Synthon B.V. | Process for preparation of axitinib |
EP3965743A1 (en) | 2019-05-09 | 2022-03-16 | Synthon B.V. | Pharmaceutical composition comprising axitinib |
EP3990635A1 (en) | 2019-06-27 | 2022-05-04 | Rigontec GmbH | Design method for optimized rig-i ligands |
US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN114585623A (zh) | 2019-08-02 | 2022-06-03 | 梅尔莎纳医疗公司 | 双[N-((5-氨基甲酰基)-1H-苯并[d]咪唑-2-基)吡唑-5-甲酰胺]衍生物和相关化合物作为STING(干扰素基因刺激物)激动剂用于治疗癌症 |
CA3150701A1 (en) | 2019-08-15 | 2021-02-18 | Black Diamond Therapeutics, Inc. | Alkynyl quinazoline compounds |
CN112442011B (zh) * | 2019-08-30 | 2023-11-14 | 润佳(苏州)医药科技有限公司 | 一种前药化合物及其在治疗癌症方面的应用 |
AU2020338490A1 (en) * | 2019-08-30 | 2022-03-17 | Risen (Suzhou) Pharma Tech Co., Ltd. | Prodrugs of the tyrosine kinase inhibitor for treating cancer |
CN112442010B (zh) * | 2019-08-30 | 2023-10-03 | 润佳(苏州)医药科技有限公司 | 一类前药化合物及其在治疗癌症方面的应用 |
IL291901A (en) | 2019-10-14 | 2022-06-01 | Incyte Corp | Bicyclyl heterocycles as fgr suppressors |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN112694474B (zh) * | 2019-10-23 | 2022-03-18 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
JP2023505257A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤の誘導体 |
EP4069683A1 (en) | 2019-12-06 | 2022-10-12 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
CN111829859B (zh) * | 2020-01-20 | 2024-01-05 | 北京林业大学 | 一种高效杨树种子透明染色及其三维成像的方法 |
AU2021207313A1 (en) | 2020-02-18 | 2022-07-28 | Novo Nordisk A/S | Pharmaceutical formulations |
BR102020005423A2 (pt) * | 2020-03-18 | 2021-09-28 | Faculdades Catolicas | Compostos n-acil-hidrazônicos, uso no tratamento de agregopatias degenerativas amiloides e não-amiloides, e composição farmacêutica |
WO2021195206A1 (en) | 2020-03-24 | 2021-09-30 | Black Diamond Therapeutics, Inc. | Polymorphic forms and related uses |
TW202202493A (zh) | 2020-05-06 | 2022-01-16 | 美商默沙東藥廠 | Il4i1抑制劑及使用方法 |
WO2021232367A1 (zh) * | 2020-05-21 | 2021-11-25 | 四川大学 | 3-乙烯基吲唑类衍生物及其制备方法和用途 |
CN113943271B (zh) * | 2020-07-15 | 2023-11-14 | 鲁南制药集团股份有限公司 | 一种阿昔替尼晶型及其制备方法 |
CN112028831A (zh) * | 2020-09-24 | 2020-12-04 | 山东大学 | 一种苯并吡唑类化合物、其制备方法及作为抗肿瘤药物的应用 |
AU2021409561A1 (en) | 2020-12-22 | 2023-07-06 | Nikang Therapeutics, Inc. | Compounds for degrading cyclin-dependent kinase 2 via ubiquitin proteosome pathway |
CA3208313A1 (en) | 2021-01-13 | 2022-07-21 | Monte Rosa Therapeutics Ag | Isoindolinone compounds |
WO2022170052A1 (en) | 2021-02-05 | 2022-08-11 | Black Diamond Therapeutics, Inc. | Quinazoline derivatives, pyridopyrimidine derivatives, pyrimidopyrimidine derivatives, and uses thereof |
EP4323350A1 (en) | 2021-04-14 | 2024-02-21 | Monte Rosa Therapeutics AG | Isoindolinone compounds |
EP4323349A1 (en) | 2021-04-14 | 2024-02-21 | Monte Rosa Therapeutics AG | Isoindolinone amide compounds useful to treat diseases associated with gspt1 |
WO2022227015A1 (en) | 2021-04-30 | 2022-11-03 | Merck Sharp & Dohme Corp. | Il4i1 inhibitors and methods of use |
CA3220274A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
TW202317589A (zh) | 2021-07-14 | 2023-05-01 | 美商尼坎醫療公司 | 作為kras抑制劑的伸烷基衍生物 |
CN115701423A (zh) * | 2021-08-02 | 2023-02-10 | 沈阳化工大学 | 三氟乙基硫醚(亚砜)取代苯类化合物的制备方法及其中间体 |
US20230303509A1 (en) | 2022-03-28 | 2023-09-28 | Nikang Therapeutics, Inc. | Sulfonamido derivatives as cyclin-dependent kinase 2 inhibitors |
EP4282415A1 (en) | 2022-05-26 | 2023-11-29 | Genepharm S.A. | A stable tablet composition of axitinib |
WO2023240024A1 (en) | 2022-06-08 | 2023-12-14 | Nikang Therapeutics, Inc. | Sulfamide derivatives as cyclin-dependent kinase 2 inhibitors |
WO2024032584A1 (zh) * | 2022-08-08 | 2024-02-15 | 苏州必扬医药科技有限公司 | 一种蛋白酪氨酸激酶抑制剂及其医疗用途 |
WO2024102849A1 (en) | 2022-11-11 | 2024-05-16 | Nikang Therapeutics, Inc. | Bifunctional compounds containing 2,5-substituted pyrimidine derivatives for degrading cyclin-dependent kinase 2 via ubiquitin proteasome pathway |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5625031A (en) * | 1994-02-08 | 1997-04-29 | Bristol-Myers Squibb Company | Peptide inhibitors of the p33cdk2 and p34cdc2 cell cycle regulatory kinases and human papillomavirus E7 oncoprotein |
US5631156A (en) * | 1994-06-21 | 1997-05-20 | The University Of Michigan | DNA encoding and 18 KD CDK6 inhibiting protein |
CN1165482A (zh) * | 1994-11-10 | 1997-11-19 | 科西雷佩蒂斯公司 | 用作蛋白激酶抑制剂的吡唑药物组合物 |
ZA951822B (en) * | 1994-12-23 | 1996-09-26 | Glaxo Group Ltd | Chemical compounds |
US5710173A (en) * | 1995-06-07 | 1998-01-20 | Sugen, Inc. | Thienyl compounds for inhibition of cell proliferative disorders |
US5733920A (en) * | 1995-10-31 | 1998-03-31 | Mitotix, Inc. | Inhibitors of cyclin dependent kinases |
US5760028A (en) * | 1995-12-22 | 1998-06-02 | The Dupont Merck Pharmaceutical Company | Integrin receptor antagonists |
DE69734149T2 (de) * | 1996-03-15 | 2006-07-06 | Astrazeneca Ab | Cinoline derivate und verwendung als heilmittel |
WO1997048697A1 (en) * | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
CN1234031A (zh) * | 1996-09-04 | 1999-11-03 | 辉瑞大药厂 | 吲唑衍生物及其作为磷酸二酯酶(pde)iv型和肿瘤坏死因子(tnf)产生的抑制剂的应用 |
IL135574A0 (en) * | 1997-10-27 | 2001-05-20 | Agouron Pharma | Substituted 4-amino-thiazol-2-yl compounds as cdk inhibitors |
ID24942A (id) * | 1997-11-04 | 2000-08-31 | Pfizer Prod Inc | Senyawa terapi aktif yang berdasarkan penggantian bioisoster katekol dengan indazole pada inhibitor pde4 |
ID23921A (id) * | 1997-11-04 | 2000-05-25 | Pfizer Prod Inc | Penggantian indazola bioisostere katekol pada senyawa-senyawa aktif untuk terapi |
PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
-
2000
- 2000-06-28 PE PE2000000663A patent/PE20010306A1/es not_active IP Right Cessation
- 2000-06-29 GT GT200000107A patent/GT200000107A/es unknown
- 2000-06-30 HU HU0202490A patent/HU228502B1/hu active Protection Beyond IP Right Term
- 2000-06-30 EA EA200200120A patent/EA004460B1/ru active Protection Beyond IP Right Term
- 2000-06-30 DE DE60036879T patent/DE60036879T2/de not_active Expired - Lifetime
- 2000-06-30 DK DK00943375T patent/DK1218348T3/da active
- 2000-06-30 CN CNB03154858XA patent/CN1234693C/zh not_active Expired - Lifetime
- 2000-06-30 KR KR1020017016850A patent/KR100529639B1/ko active IP Right Grant
- 2000-06-30 PT PT00943375T patent/PT1218348E/pt unknown
- 2000-06-30 GE GE4718A patent/GEP20063885B/en unknown
- 2000-06-30 MY MYPI20003017A patent/MY139999A/en unknown
- 2000-06-30 TN TNTNSN00146A patent/TNSN00146A1/fr unknown
- 2000-06-30 WO PCT/US2000/018263 patent/WO2001002369A2/en active Application Filing
- 2000-06-30 PL PL355757A patent/PL212108B1/pl unknown
- 2000-06-30 IL IL14671000A patent/IL146710A0/xx active Protection Beyond IP Right Term
- 2000-06-30 DK DK05015902T patent/DK1614683T3/da active
- 2000-06-30 SV SV2000000121A patent/SV2002000121A/es unknown
- 2000-06-30 MY MYPI20033472A patent/MY137622A/en unknown
- 2000-06-30 RS YUP-929/01A patent/RS50339B/sr unknown
- 2000-06-30 PT PT05015902T patent/PT1614683E/pt unknown
- 2000-06-30 ES ES00943375T patent/ES2293906T3/es not_active Expired - Lifetime
- 2000-06-30 CZ CZ20014634A patent/CZ301667B6/cs unknown
- 2000-06-30 OA OA1200100348A patent/OA11980A/en unknown
- 2000-06-30 NZ NZ516676A patent/NZ516676A/en not_active IP Right Cessation
- 2000-06-30 CN CNB008098212A patent/CN1137884C/zh not_active Expired - Lifetime
- 2000-06-30 AT AT00943375T patent/ATE376543T1/de active
- 2000-06-30 BR BRPI0012352A patent/BRPI0012352B8/pt not_active IP Right Cessation
- 2000-06-30 EP EP00943375A patent/EP1218348B1/en not_active Expired - Lifetime
- 2000-06-30 ES ES05015902T patent/ES2296014T3/es not_active Expired - Lifetime
- 2000-06-30 AP APAP/P/2002/002392A patent/AP1486A/en active
- 2000-06-30 EP EP05015902A patent/EP1614683B1/en not_active Expired - Lifetime
- 2000-06-30 DE DE60037211T patent/DE60037211T2/de not_active Expired - Lifetime
- 2000-06-30 JP JP2001507809A patent/JP3878849B2/ja not_active Expired - Lifetime
- 2000-06-30 AR ARP000103381A patent/AR035554A1/es active IP Right Grant
- 2000-06-30 ME MEP-2008-451A patent/ME00385B/me unknown
- 2000-06-30 DZ DZ003191A patent/DZ3191A1/xx active
- 2000-06-30 SI SI200030972T patent/SI1218348T1/sl unknown
- 2000-06-30 SK SK1925-2001A patent/SK286936B6/sk not_active IP Right Cessation
- 2000-06-30 UY UY26231A patent/UY26231A1/es not_active IP Right Cessation
- 2000-06-30 UA UA2001129216A patent/UA66933C2/uk unknown
- 2000-06-30 CA CA002383630A patent/CA2383630C/en not_active Expired - Lifetime
- 2000-06-30 AU AU57852/00A patent/AU777701B2/en active Active
- 2000-06-30 SI SI200030976T patent/SI1614683T1/sl unknown
- 2000-06-30 EE EEP200100717A patent/EE05585B1/xx active Protection Beyond IP Right Term
- 2000-06-30 MX MXPA01012795A patent/MXPA01012795A/es active IP Right Grant
- 2000-07-02 JO JO2000105A patent/JO2319B1/en active
- 2000-07-03 PA PA20008498001A patent/PA8498001A1/es unknown
- 2000-07-04 CO CO00049777A patent/CO5190686A1/es active IP Right Grant
-
2001
- 2001-11-28 NO NO20015797A patent/NO322507B1/no not_active IP Right Cessation
- 2001-12-03 CR CR6517A patent/CR6517A/es unknown
- 2001-12-06 ZA ZA200110061A patent/ZA200110061B/en unknown
- 2001-12-19 IS IS6207A patent/IS2791B/is unknown
- 2001-12-28 MA MA26455A patent/MA26803A1/fr unknown
-
2002
- 2002-02-01 BG BG106380A patent/BG66070B1/bg unknown
- 2002-02-04 HR HR20020109A patent/HRP20020109B1/xx not_active IP Right Cessation
-
2003
- 2003-02-12 HK HK04107797A patent/HK1065037A1/xx not_active IP Right Cessation
- 2003-02-12 HK HK03101000A patent/HK1048813A1/xx not_active IP Right Cessation
-
2006
- 2006-02-06 NO NO20060596A patent/NO20060596L/no not_active Application Discontinuation
- 2006-05-10 HK HK06105462A patent/HK1085470A1/xx not_active IP Right Cessation
- 2006-08-30 JP JP2006232927A patent/JP3969669B2/ja not_active Expired - Lifetime
-
2008
- 2008-01-18 CY CY20081100072T patent/CY1107147T1/el unknown
- 2008-01-18 CY CY20081100075T patent/CY1107148T1/el unknown
- 2008-04-03 AR ARP080101395A patent/AR065937A2/es unknown
- 2008-08-08 CR CR10194A patent/CR10194A/es not_active Application Discontinuation
-
2013
- 2013-02-15 FR FR13C0010C patent/FR13C0010I2/fr active Active
- 2013-02-20 LU LU92154C patent/LU92154I2/fr unknown
- 2013-02-26 NO NO2013004C patent/NO2013004I2/no unknown
- 2013-02-26 BE BE2013C015C patent/BE2013C015I2/fr unknown
- 2013-03-01 CY CY2013009C patent/CY2013009I1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HU228502B1 (en) | Indazole derivatives and pharmaceutical compositions for inhibiting protein kinases, and methods for their use | |
US6884890B2 (en) | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use | |
TWI344961B (en) | Novel indazole derivative | |
TW200911233A (en) | Substituted indazole derivatives active as kinase inhibitors | |
US20090291968A1 (en) | Substituted indazole derivatives, their manufacture and use as pharmaceutical agents | |
HRP20020675A2 (en) | Indazole compounds, pharmaceutical compositions and methods for mediating or inhibiting cell poliferation | |
JP2013544872A (ja) | 神経変性疾患の治療のための新規化合物 | |
JP2007509173A (ja) | インドリノン誘導体類及び疾病状態、例えば癌の処理へのそれらの使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
HC9A | Change of name, address |
Owner name: AGOURON PHARMACEUTICALS, INC., US Free format text: FORMER OWNER(S): AGOURON PHARMACEUTICALS, INC., US |
|
AA1S | Information on application for a supplementary protection certificate |
Free format text: PRODUCT NAME: AXITINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS; REG. NO/DATE: EU/1/12/777/001-006 20120903 Spc suppl protection certif: S1300041 Filing date: 20130822 Expiry date: 20200630 |
|
FG4S | Grant of supplementary protection certificate |
Free format text: PRODUCT NAME: AXITINIB AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS; REGISTRATION NO/DATE: EU/1/12/777/001-006 20120903 Spc suppl protection certif: S1300041 Filing date: 20130822 Expiry date: 20200630 Extension date: 20250630 |
|
GB9A | Succession in title |
Owner name: AGOURON PHARMACEUTICALS, LLC, US Free format text: FORMER OWNER(S): AGOURON PHARMACEUTICALS, INC., US; AGOURON PHARMACEUTICALS, INC., US |