BG106276A - Диаминотиазоли и употребата им за инхибиране на протеин кинази - Google Patents
Диаминотиазоли и употребата им за инхибиране на протеин кинази Download PDFInfo
- Publication number
- BG106276A BG106276A BG106276A BG10627602A BG106276A BG 106276 A BG106276 A BG 106276A BG 106276 A BG106276 A BG 106276A BG 10627602 A BG10627602 A BG 10627602A BG 106276 A BG106276 A BG 106276A
- Authority
- BG
- Bulgaria
- Prior art keywords
- formula
- group
- aryl
- amino
- substituted
- Prior art date
Links
- 102000001253 Protein Kinase Human genes 0.000 title claims abstract description 32
- 108060006633 protein kinase Proteins 0.000 title claims abstract description 32
- WKXCZMFWXZRMEZ-UHFFFAOYSA-N 1,3-thiazole-2,4-diamine Chemical class NC1=CSC(N)=N1 WKXCZMFWXZRMEZ-UHFFFAOYSA-N 0.000 title abstract description 3
- 230000002401 inhibitory effect Effects 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 230000000694 effects Effects 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 230000004663 cell proliferation Effects 0.000 claims abstract description 18
- 230000033115 angiogenesis Effects 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 heteroaryl radical Chemical class 0.000 claims description 310
- 125000003118 aryl group Chemical group 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 22
- 239000002207 metabolite Substances 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000011737 fluorine Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 150000003254 radicals Chemical class 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 125000004404 heteroalkyl group Chemical group 0.000 claims 4
- 229940002612 prodrug Drugs 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 22
- 201000011510 cancer Diseases 0.000 abstract description 17
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 14
- 229940127557 pharmaceutical product Drugs 0.000 abstract description 11
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 8
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 8
- 230000019491 signal transduction Effects 0.000 abstract description 5
- 201000004681 Psoriasis Diseases 0.000 abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 208000010412 Glaucoma Diseases 0.000 abstract description 2
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 2
- 201000003142 neovascular glaucoma Diseases 0.000 abstract description 2
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 238000005481 NMR spectroscopy Methods 0.000 description 94
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 92
- 239000000243 solution Substances 0.000 description 86
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 239000002904 solvent Substances 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000003795 chemical substances by application Substances 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 31
- 238000003556 assay Methods 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 229910001868 water Inorganic materials 0.000 description 24
- 238000011282 treatment Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- 230000005764 inhibitory process Effects 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000012360 testing method Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 108091000080 Phosphotransferase Proteins 0.000 description 19
- 102000020233 phosphotransferase Human genes 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000012267 brine Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 102000016736 Cyclin Human genes 0.000 description 11
- 108050006400 Cyclin Proteins 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000022131 cell cycle Effects 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 8
- 239000000969 carrier Substances 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 102000013009 Pyruvate Kinase Human genes 0.000 description 7
- 108020005115 Pyruvate Kinase Proteins 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 7
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 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 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 6
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 6
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 230000032823 cell division Effects 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 239000003102 growth factor Substances 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 210000001525 retina Anatomy 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 241000701447 unidentified baculovirus Species 0.000 description 6
- 108091007914 CDKs Proteins 0.000 description 5
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 5
- 231100000277 DNA damage Toxicity 0.000 description 5
- 241000238631 Hexapoda Species 0.000 description 5
- 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 5
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000035578 autophosphorylation Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 5
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- QZLSBOVWPHXCLT-UHFFFAOYSA-N 5-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)S1 QZLSBOVWPHXCLT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
- 108010058545 Cyclin D3 Proteins 0.000 description 4
- 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 4
- 239000006184 cosolvent Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229940014259 gelatin Drugs 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate group Chemical group [N+](=O)([O-])[O-] NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000003909 protein kinase inhibitor Substances 0.000 description 4
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- LTPSRQRIPCVMKQ-UHFFFAOYSA-N 2-amino-5-methylbenzenesulfonic acid Chemical compound CC1=CC=C(N)C(S(O)(=O)=O)=C1 LTPSRQRIPCVMKQ-UHFFFAOYSA-N 0.000 description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 101150050673 CHK1 gene Proteins 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 102100027370 Parathymosin Human genes 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000004992 fission Effects 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 229960005150 glycerol Drugs 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- WYQQGYULUDOPRU-UHFFFAOYSA-M potassium;2,3,4,5,6-pentachlorophenolate Chemical compound [K+].[O-]C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl WYQQGYULUDOPRU-UHFFFAOYSA-M 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000001210 retinal vessel Anatomy 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 2
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- LVRFTAZAXQPQHI-UHFFFAOYSA-N 2-hydroxy-4-methylvaleric acid Chemical compound CC(C)CC(O)C(O)=O LVRFTAZAXQPQHI-UHFFFAOYSA-N 0.000 description 2
- YSNKGJCEHOJIDK-UHFFFAOYSA-N 3-(chloromethyl)-1,2,4-oxadiazole Chemical compound ClCC=1N=CON=1 YSNKGJCEHOJIDK-UHFFFAOYSA-N 0.000 description 2
- VNEOHNUYPRAJMX-UHFFFAOYSA-N 3-[[2-[[2-amino-3-(1h-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[1-(butoxycarbonylamino)-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid Chemical compound C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(CC(C)C)C(=O)NC(CC(O)=O)C(=O)NC(C(=O)NC(=O)OCCCC)CC1=CC=CC=C1 VNEOHNUYPRAJMX-UHFFFAOYSA-N 0.000 description 2
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 2
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- HSZLBBZSPHXHDJ-UHFFFAOYSA-N 4-[(4-amino-5-cyano-1,3-thiazol-2-yl)amino]benzenesulfonamide Chemical compound S1C(C#N)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 HSZLBBZSPHXHDJ-UHFFFAOYSA-N 0.000 description 2
- ZFOXYMYPSAEQEA-UHFFFAOYSA-N 4-amino-2-(4-sulfamoylanilino)-1,3-thiazole-5-carbothioamide Chemical compound NC1=C(C(=S)N)SC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 ZFOXYMYPSAEQEA-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- OMNHTTWQSSUZHO-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(C)=C1O OMNHTTWQSSUZHO-UHFFFAOYSA-N 0.000 description 2
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CRJMUPLBKOEEGR-UHFFFAOYSA-N 5-(3,4,5-trimethoxyphenyl)-1,3-thiazole-2,4-diamine Chemical compound COc1cc(cc(OC)c1OC)-c1sc(N)nc1N CRJMUPLBKOEEGR-UHFFFAOYSA-N 0.000 description 2
- FVHWIBHCJNCRAI-UHFFFAOYSA-N 5-chloro-n-[3-[2-(2,4-diamino-1,3-thiazol-5-yl)-1,3-thiazol-4-yl]phenyl]thiophene-2-carboxamide Chemical compound S1C(N)=NC(N)=C1C1=NC(C=2C=C(NC(=O)C=3SC(Cl)=CC=3)C=CC=2)=CS1 FVHWIBHCJNCRAI-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
- 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
- 102100034594 Angiopoietin-1 Human genes 0.000 description 2
- 108010048154 Angiopoietin-1 Proteins 0.000 description 2
- 101150032275 CDPK2 gene Proteins 0.000 description 2
- 101150082449 CDPK4 gene Proteins 0.000 description 2
- 101150053275 CPK2 gene Proteins 0.000 description 2
- 101150058743 CPK4 gene Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- 108010068192 Cyclin A Proteins 0.000 description 2
- 108010058546 Cyclin D1 Proteins 0.000 description 2
- 102100025191 Cyclin-A2 Human genes 0.000 description 2
- 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 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 2
- 102100023077 Extracellular matrix protein 2 Human genes 0.000 description 2
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 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
- 101001050211 Homo sapiens Extracellular matrix protein 2 Proteins 0.000 description 2
- 101000606465 Homo sapiens Inactive tyrosine-protein kinase 7 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102100039813 Inactive tyrosine-protein kinase 7 Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 101100059586 Oryza sativa subsp. japonica CPK19 gene Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102100037483 POU domain, class 6, transcription factor 1 Human genes 0.000 description 2
- 101710196406 POU domain, class 6, transcription factor 1 Proteins 0.000 description 2
- 108010063843 Phencyclidine Receptors Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000006957 competitive inhibition Effects 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 102000048620 human CHEK1 Human genes 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 238000000338 in vitro Methods 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
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008188 pellet 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
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- 230000006459 vascular development Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- YNEUKTPESKGPNQ-VIFPVBQESA-N (1s)-1-amino-3-phenylpropan-1-ol Chemical compound N[C@@H](O)CCC1=CC=CC=C1 YNEUKTPESKGPNQ-VIFPVBQESA-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
- ARLKVQYMFRECLV-JSGCOSHPSA-N (2s)-2-[[(2s)-2-amino-3-(1h-indol-3-yl)propanoyl]amino]-4-methylsulfanylbutanamide Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCSC)C(N)=O)=CNC2=C1 ARLKVQYMFRECLV-JSGCOSHPSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- QHHHLHCCVDMOJI-UHFFFAOYSA-N 1,3-thiazol-4-amine Chemical class NC1=CSC=N1 QHHHLHCCVDMOJI-UHFFFAOYSA-N 0.000 description 1
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-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
- HTFUNTJXBMVMGT-UHFFFAOYSA-N 1-oxothiophen-3-amine Chemical compound NC1=CS(C=C1)=O HTFUNTJXBMVMGT-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- MQGBARXPCXAFRZ-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-carboxylic acid Chemical compound CC1=NC(C)=C(C(O)=O)S1 MQGBARXPCXAFRZ-UHFFFAOYSA-N 0.000 description 1
- SPMLMLQATWNZEE-UHFFFAOYSA-N 2-(chloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CCl)=NC2=C1 SPMLMLQATWNZEE-UHFFFAOYSA-N 0.000 description 1
- BWCCPOQIMGGGQX-UHFFFAOYSA-N 2-(chloromethyl)-4,6-dimethoxypyrimidine Chemical compound COC1=CC(OC)=NC(CCl)=N1 BWCCPOQIMGGGQX-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 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
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- QCXCIYPOMMIBHO-UHFFFAOYSA-N 2-methyl-1,3-thiazole-5-carboxylic acid Chemical compound CC1=NC=C(C(O)=O)S1 QCXCIYPOMMIBHO-UHFFFAOYSA-N 0.000 description 1
- FJNLCHNQVJVCPY-UHFFFAOYSA-N 2-n-methoxy-2-n-methyl-4-n,6-n-dipropyl-1,3,5-triazine-2,4,6-triamine Chemical compound CCCNC1=NC(NCCC)=NC(N(C)OC)=N1 FJNLCHNQVJVCPY-UHFFFAOYSA-N 0.000 description 1
- GILCFOZQOQMDFK-UHFFFAOYSA-N 2-n-phenyl-5-pyridin-2-yl-1,3-thiazole-2,4-diamine Chemical compound S1C(C=2N=CC=CC=2)=C(N)N=C1NC1=CC=CC=C1 GILCFOZQOQMDFK-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- CKQHAYFOPRIUOM-UHFFFAOYSA-N 3'-Aminoacetophenone Chemical compound CC(=O)C1=CC=CC(N)=C1 CKQHAYFOPRIUOM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RSSBMWQNIDHJNS-UHFFFAOYSA-N 3-(chloromethyl)-5-(thiadiazol-4-yl)-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C=2N=NSC=2)=N1 RSSBMWQNIDHJNS-UHFFFAOYSA-N 0.000 description 1
- FEXTXBAFBURKGS-UHFFFAOYSA-N 3-(chloromethyl)-5-methyl-1,2-oxazole Chemical compound CC1=CC(CCl)=NO1 FEXTXBAFBURKGS-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
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- NUSXEDNPFNWFDQ-UHFFFAOYSA-N 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(CCl)C(Cl)=C1 NUSXEDNPFNWFDQ-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
- PUZFMDAJRJLNJN-UHFFFAOYSA-N 3-methyloctanamide Chemical compound CCCCCC(C)CC(N)=O PUZFMDAJRJLNJN-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- RPJMTTUATVKBMN-UHFFFAOYSA-N 4-[[4-amino-5-(4-phenyl-1,3-thiazol-2-yl)-1,3-thiazol-2-yl]amino]benzenesulfonamide Chemical compound S1C(C=2SC=C(N=2)C=2C=CC=CC=2)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 RPJMTTUATVKBMN-UHFFFAOYSA-N 0.000 description 1
- JOYLNPOUQUOJQV-UHFFFAOYSA-N 4-[[4-amino-5-(5-nitro-1,3-benzothiazol-2-yl)-1,3-thiazol-2-yl]amino]benzenesulfonamide Chemical compound S1C(C=2SC3=CC=C(C=C3N=2)[N+]([O-])=O)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 JOYLNPOUQUOJQV-UHFFFAOYSA-N 0.000 description 1
- JCVPNINLSDOPHJ-UHFFFAOYSA-N 4-amino-1,3-thiazole-5-carbothioamide Chemical compound NC=1N=CSC=1C(N)=S JCVPNINLSDOPHJ-UHFFFAOYSA-N 0.000 description 1
- XPXLWEBNQPZCBC-UHFFFAOYSA-N 4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazole-5-carbonitrile Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C#N)=C1 XPXLWEBNQPZCBC-UHFFFAOYSA-N 0.000 description 1
- WSVCIWJKLYVDLA-UHFFFAOYSA-N 4-amino-2-(4-propan-2-ylanilino)-1,3-thiazole-5-carbothioamide Chemical compound C1=CC(C(C)C)=CC=C1NC1=NC(N)=C(C(N)=S)S1 WSVCIWJKLYVDLA-UHFFFAOYSA-N 0.000 description 1
- NYEMVPGQXLAKEH-UHFFFAOYSA-N 4-amino-2-(4-sulfamoylanilino)-1,3-thiazole-5-carboxamide Chemical compound NC1=C(C(=O)N)SC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 NYEMVPGQXLAKEH-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 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
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- IMDUFDNFSJWYQT-UHFFFAOYSA-N 4-isothiocyanatobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(N=C=S)C=C1 IMDUFDNFSJWYQT-UHFFFAOYSA-N 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
- HRSFRTHRNQEVAS-UHFFFAOYSA-N 5-(6-bromopyridin-2-yl)-2-n-(3,4,5-trimethoxyphenyl)-1,3-thiazole-2,4-diamine Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2N=C(Br)C=CC=2)=C1 HRSFRTHRNQEVAS-UHFFFAOYSA-N 0.000 description 1
- VPRXACKBZBROKZ-UHFFFAOYSA-N 5-[3-(5-amino-2-fluorophenyl)-1,2,4-oxadiazol-5-yl]-2-n-(3,4,5-trimethoxyphenyl)-1,3-thiazole-2,4-diamine Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2ON=C(N=2)C=2C(=CC=C(N)C=2)F)=C1 VPRXACKBZBROKZ-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- COWZPSUDTMGBAT-UHFFFAOYSA-N 5-bromothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)S1 COWZPSUDTMGBAT-UHFFFAOYSA-N 0.000 description 1
- FFFMIFUBJZBTCG-UHFFFAOYSA-N 5-chloro-3-(chloromethyl)-1,2,4-thiadiazole Chemical compound ClCC1=NSC(Cl)=N1 FFFMIFUBJZBTCG-UHFFFAOYSA-N 0.000 description 1
- MULZWPFQTUDZPD-UHFFFAOYSA-N 5-methyl-2-phenyl-1,3-oxazole Chemical compound O1C(C)=CN=C1C1=CC=CC=C1 MULZWPFQTUDZPD-UHFFFAOYSA-N 0.000 description 1
- BXANGIZBUPAFHR-UHFFFAOYSA-N 5-quinolin-2-yl-2-n-(3,4,5-trimethoxyphenyl)-1,3-thiazole-2,4-diamine Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2N=C3C=CC=CC3=CC=2)=C1 BXANGIZBUPAFHR-UHFFFAOYSA-N 0.000 description 1
- ZLKMOIHCHCMSFW-UHFFFAOYSA-N 6-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(Cl)=N1 ZLKMOIHCHCMSFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 241001367053 Autographa gamma Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 108091005932 CCKBR Proteins 0.000 description 1
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 description 1
- 102100027221 CD81 antigen Human genes 0.000 description 1
- 101150091140 CDPK1 gene Proteins 0.000 description 1
- GRCMZHNTKLXDAP-UHFFFAOYSA-N COC1=C(OC)C(OC)=CC(C2(N)SC=C(N)N2)=C1 Chemical compound COC1=C(OC)C(OC)=CC(C2(N)SC=C(N)N2)=C1 GRCMZHNTKLXDAP-UHFFFAOYSA-N 0.000 description 1
- 101150108143 CPK1 gene Proteins 0.000 description 1
- 101100135798 Caenorhabditis elegans pcp-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000252254 Catostomidae Species 0.000 description 1
- 108010019244 Checkpoint Kinase 1 Proteins 0.000 description 1
- 102000006459 Checkpoint Kinase 1 Human genes 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 102000002427 Cyclin B Human genes 0.000 description 1
- 108010068150 Cyclin B Proteins 0.000 description 1
- 102000003909 Cyclin E Human genes 0.000 description 1
- 108090000257 Cyclin E Proteins 0.000 description 1
- 102100028203 Cytochrome c oxidase subunit 3 Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 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
- 230000012746 DNA damage checkpoint Effects 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000031448 Genomic Instability 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
- 235000009438 Gossypium Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 1
- 101000861034 Homo sapiens Cytochrome c oxidase subunit 3 Proteins 0.000 description 1
- 101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 description 1
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
- 101000631760 Homo sapiens Sodium channel protein type 1 subunit alpha Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010058490 Hyperoxia Diseases 0.000 description 1
- 206010021143 Hypoxia 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
- PSFFSTZCRIOTHZ-UHFFFAOYSA-N NC=1N=C(SC1C=1N(C=CN1)CC1=CC=C(C=C1)Cl)NC1=CC=CC=C1S(=O)(=O)N Chemical compound NC=1N=C(SC1C=1N(C=CN1)CC1=CC=C(C=C1)Cl)NC1=CC=CC=C1S(=O)(=O)N PSFFSTZCRIOTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910017912 NH2OH Inorganic materials 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-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
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 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
- 241000589516 Pseudomonas Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 229910006074 SO2NH2 Inorganic materials 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 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
- 229910003691 SiBr Inorganic materials 0.000 description 1
- 102100028910 Sodium channel protein type 1 subunit alpha Human genes 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101100137008 Streptomyces hygroscopicus Pmms gene Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
- 239000007983 Tris buffer Substances 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- YZVSGSJXPAJXOW-UHFFFAOYSA-N [3-[5-(2,4-diamino-1,3-thiazol-5-yl)-1,2,4-oxadiazol-3-yl]phenyl]carbamic acid Chemical compound S1C(N)=NC(N)=C1C1=NC(C=2C=C(NC(O)=O)C=CC=2)=NO1 YZVSGSJXPAJXOW-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- MANVMTSCCSAYSN-UHFFFAOYSA-N acetonitrile;2-methylpropan-2-ol Chemical compound CC#N.CC(C)(C)O MANVMTSCCSAYSN-UHFFFAOYSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 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
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-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
- 125000002947 alkylene 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
- BCDGQXUMWHRQCB-UHFFFAOYSA-N aminoacetone Chemical compound CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension 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
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- YWBUHTQWQACROE-UHFFFAOYSA-N benzyl n-[3-[2-[4-amino-2-(4-sulfamoylanilino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]carbamate Chemical compound S1C(C=2SC=C(N=2)C=2C=C(NC(=O)OCC=3C=CC=CC=3)C=CC=2)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 YWBUHTQWQACROE-UHFFFAOYSA-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
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-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
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Chemical class 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
- 235000021277 colostrum Nutrition 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-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
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([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
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 125000005534 decanoate group Chemical class 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 229940124642 endogenous agent Drugs 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 231100000584 environmental toxicity Toxicity 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 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
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-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
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 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
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- VPFMEXRVUOPYRG-UHFFFAOYSA-N hex-5-ynoic acid Chemical compound OC(=O)CCCC#C VPFMEXRVUOPYRG-UHFFFAOYSA-N 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 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
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 238000007327 hydrogenolysis 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
- 230000000222 hyperoxic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 229910052742 iron Inorganic materials 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
- 229940047889 isobutyramide Drugs 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 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 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [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
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Chemical group 0.000 description 1
- 239000002184 metal Chemical group 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 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
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- HDSHZLZMDAJJQD-UHFFFAOYSA-N n-(3-acetylphenyl)-5-chlorothiophene-2-carboxamide Chemical compound CC(=O)C1=CC=CC(NC(=O)C=2SC(Cl)=CC=2)=C1 HDSHZLZMDAJJQD-UHFFFAOYSA-N 0.000 description 1
- PWDMBYJRTAANCD-UHFFFAOYSA-N n-[3-[2-(2-acetamido-4-amino-1,3-thiazol-5-yl)-1,3-thiazol-4-yl]phenyl]-5-chlorothiophene-2-carboxamide Chemical compound S1C(NC(=O)C)=NC(N)=C1C1=NC(C=2C=C(NC(=O)C=3SC(Cl)=CC=3)C=CC=2)=CS1 PWDMBYJRTAANCD-UHFFFAOYSA-N 0.000 description 1
- WMGQGCCMVSDQRY-UHFFFAOYSA-N n-[3-[2-(2-acetamido-4-amino-1,3-thiazol-5-yl)-1,3-thiazol-4-yl]phenyl]benzamide Chemical compound S1C(NC(=O)C)=NC(N)=C1C1=NC(C=2C=C(NC(=O)C=3C=CC=CC=3)C=CC=2)=CS1 WMGQGCCMVSDQRY-UHFFFAOYSA-N 0.000 description 1
- QSSIYKLZUGWETA-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(1,3-benzodioxol-5-ylamino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]benzamide Chemical compound NC=1N=C(NC=2C=C3OCOC3=CC=2)SC=1C(SC=1)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=CC=C1 QSSIYKLZUGWETA-UHFFFAOYSA-N 0.000 description 1
- KNGHSLIEGYQZIC-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]benzamide Chemical compound NC=1N=C(NC=2C=C3OCCOC3=CC=2)SC=1C(SC=1)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=CC=C1 KNGHSLIEGYQZIC-UHFFFAOYSA-N 0.000 description 1
- OKZHLVGCEWXZKK-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(2-phenylethylamino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]benzamide Chemical compound S1C(C=2SC=C(N=2)C=2C=C(NC(=O)C=3C=CC=CC=3)C=CC=2)=C(N)N=C1NCCC1=CC=CC=C1 OKZHLVGCEWXZKK-UHFFFAOYSA-N 0.000 description 1
- FUGSKXRVNNOHKU-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]-5-bromofuran-2-carboxamide Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2SC=C(N=2)C=2C=C(NC(=O)C=3OC(Br)=CC=3)C=CC=2)=C1 FUGSKXRVNNOHKU-UHFFFAOYSA-N 0.000 description 1
- YKQKILMRTKIWFL-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]-5-chlorothiophene-2-carboxamide Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2SC=C(N=2)C=2C=C(NC(=O)C=3SC(Cl)=CC=3)C=CC=2)=C1 YKQKILMRTKIWFL-UHFFFAOYSA-N 0.000 description 1
- GPQHQGPECIYVEC-UHFFFAOYSA-N n-[3-[2-[4-amino-2-(pyridin-3-ylmethylcarbamoylamino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C=C(C=CC=2)C=2N=C(SC=2)C2=C(N=C(NC(=O)NCC=3C=NC=CC=3)S2)N)=C1 GPQHQGPECIYVEC-UHFFFAOYSA-N 0.000 description 1
- GBQNNAJCDBJEIZ-UHFFFAOYSA-N n-[3-[2-[4-amino-2-[(1,4-dioxo-2,3-dihydrophthalazin-6-yl)amino]-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]phenyl]benzamide Chemical compound NC=1N=C(NC=2C=C3C(C(NNC3=O)=O)=CC=2)SC=1C(SC=1)=NC=1C(C=1)=CC=CC=1NC(=O)C1=CC=CC=C1 GBQNNAJCDBJEIZ-UHFFFAOYSA-N 0.000 description 1
- WNMGYLGYARZGMV-UHFFFAOYSA-N n-[3-[5-(4-amino-2-benzamido-1,3-thiazol-5-yl)-1,2,4-oxadiazol-3-yl]phenyl]-3-chlorobenzamide Chemical compound S1C(C=2ON=C(N=2)C=2C=C(NC(=O)C=3C=C(Cl)C=CC=3)C=CC=2)=C(N)N=C1NC(=O)C1=CC=CC=C1 WNMGYLGYARZGMV-UHFFFAOYSA-N 0.000 description 1
- LTBGJAKKIKOHSV-UHFFFAOYSA-N n-[3-[5-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]-3,5-dimethylbenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2ON=C(N=2)C=2C=C(NC(=O)C=3C=C(C)C=C(C)C=3)C=CC=2)=C1 LTBGJAKKIKOHSV-UHFFFAOYSA-N 0.000 description 1
- RNUZZENUQQQZDZ-UHFFFAOYSA-N n-[3-[5-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]-3-methylbenzamide Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2ON=C(N=2)C=2C=C(NC(=O)C=3C=C(C)C=CC=3)C=CC=2)=C1 RNUZZENUQQQZDZ-UHFFFAOYSA-N 0.000 description 1
- LVVKMLFIYNWNIG-UHFFFAOYSA-N n-[3-[5-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]acetamide Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2ON=C(N=2)C=2C=C(NC(C)=O)C=CC=2)=C1 LVVKMLFIYNWNIG-UHFFFAOYSA-N 0.000 description 1
- MGFZFZRURLWOFI-UHFFFAOYSA-N n-[3-[5-[4-amino-2-(methylcarbamoylamino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]-3-methylbenzamide Chemical compound S1C(NC(=O)NC)=NC(N)=C1C1=NC(C=2C=C(NC(=O)C=3C=C(C)C=CC=3)C=CC=2)=NO1 MGFZFZRURLWOFI-UHFFFAOYSA-N 0.000 description 1
- IGSZJONBMJNESL-UHFFFAOYSA-N n-[3-[5-[4-amino-2-(phenylcarbamoylamino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]phenyl]-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C=C(C=CC=2)C=2N=C(ON=2)C2=C(N=C(NC(=O)NC=3C=CC=CC=3)S2)N)=C1 IGSZJONBMJNESL-UHFFFAOYSA-N 0.000 description 1
- NBUKMHXINQOFDI-UHFFFAOYSA-N n-[4-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CCl)=CS1 NBUKMHXINQOFDI-UHFFFAOYSA-N 0.000 description 1
- OSQMQPAVVLXAKN-UHFFFAOYSA-N n-[5-[2-[4-amino-2-(pyridin-2-ylmethylcarbamoylamino)-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(SC=3)C3=C(N=C(NC(=O)NCC=4N=CC=CC=4)S3)N)C=2)F)=C1 OSQMQPAVVLXAKN-UHFFFAOYSA-N 0.000 description 1
- BUDOLNBNMKDLOB-OAHLLOKOSA-N n-[5-[2-[4-amino-2-[[(2r)-oxolan-2-yl]methylcarbamoylamino]-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(SC=3)C3=C(N=C(NC(=O)NC[C@@H]4OCCC4)S3)N)C=2)F)=C1 BUDOLNBNMKDLOB-OAHLLOKOSA-N 0.000 description 1
- BUDOLNBNMKDLOB-HNNXBMFYSA-N n-[5-[2-[4-amino-2-[[(2s)-oxolan-2-yl]methylcarbamoylamino]-1,3-thiazol-5-yl]-1,3-thiazol-4-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(SC=3)C3=C(N=C(NC(=O)NC[C@H]4OCCC4)S3)N)C=2)F)=C1 BUDOLNBNMKDLOB-HNNXBMFYSA-N 0.000 description 1
- JVVGVWZXAYITBX-UHFFFAOYSA-N n-[5-[5-[4-amino-2-(2-hydroxyethylcarbamoylamino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(ON=3)C3=C(N=C(NC(=O)NCCO)S3)N)C=2)F)=C1 JVVGVWZXAYITBX-UHFFFAOYSA-N 0.000 description 1
- GTVMEAWUBBAPTB-UHFFFAOYSA-N n-[5-[5-[4-amino-2-(propan-2-ylamino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(ON=3)C3=C(N=C(NC(C)C)S3)N)C=2)F)=C1 GTVMEAWUBBAPTB-UHFFFAOYSA-N 0.000 description 1
- PVRVVWDMIMCHHM-UHFFFAOYSA-N n-[5-[5-[4-amino-2-[2-(2-hydroxyethoxy)ethylcarbamoylamino]-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]-2,4-difluorophenyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(F)=C(C=3N=C(ON=3)C3=C(N=C(NC(=O)NCCOCCO)S3)N)C=2)F)=C1 PVRVVWDMIMCHHM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 239000012454 non-polar solvent Substances 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
- 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
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- ODOPKAJVFRHHGM-UHFFFAOYSA-N phenyltin Chemical compound [Sn]C1=CC=CC=C1 ODOPKAJVFRHHGM-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 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
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 230000035409 positive regulation of cell proliferation Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 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
- 230000029983 protein stabilization Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N pyrocatechol monomethyl ether Natural products COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 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
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000003860 storage Methods 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
- 235000011044 succinic acid Nutrition 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- SVYUQSKDJNCYFF-UHFFFAOYSA-N tert-butyl n-[3-[5-(4-amino-2-phenyl-1,3-thiazol-5-yl)-1,2,4-oxadiazol-3-yl]-4-methylphenyl]carbamate Chemical compound CC1=CC=C(NC(=O)OC(C)(C)C)C=C1C1=NOC(C2=C(N=C(S2)C=2C=CC=CC=2)N)=N1 SVYUQSKDJNCYFF-UHFFFAOYSA-N 0.000 description 1
- HNNRDZNSKMXALP-UHFFFAOYSA-N tert-butyl n-[5-[5-[4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazol-5-yl]-1,2,4-oxadiazol-3-yl]-4-chloro-2-fluorophenyl]carbamate Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C=2ON=C(N=2)C=2C(=CC(F)=C(NC(=O)OC(C)(C)C)C=2)Cl)=C1 HNNRDZNSKMXALP-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000008096 xylene Substances 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
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13781099P | 1999-06-04 | 1999-06-04 | |
PCT/US2000/015188 WO2000075120A1 (fr) | 1999-06-04 | 2000-06-02 | Diaminothiazoles et leur utilisation pour inhiber les proteines kinases |
Publications (1)
Publication Number | Publication Date |
---|---|
BG106276A true BG106276A (bg) | 2002-10-31 |
Family
ID=22479135
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BG106276A BG106276A (bg) | 1999-06-04 | 2002-01-03 | Диаминотиазоли и употребата им за инхибиране на протеин кинази |
Country Status (34)
Country | Link |
---|---|
US (1) | US6620828B2 (fr) |
EP (1) | EP1181283B1 (fr) |
JP (1) | JP2003501420A (fr) |
KR (1) | KR20020015333A (fr) |
CN (1) | CN1359380A (fr) |
AP (1) | AP2001002341A0 (fr) |
AT (1) | ATE288424T1 (fr) |
AU (1) | AU778071B2 (fr) |
BG (1) | BG106276A (fr) |
BR (1) | BR0011585A (fr) |
CA (1) | CA2371158A1 (fr) |
CZ (1) | CZ20014213A3 (fr) |
DE (1) | DE60017894T2 (fr) |
EA (1) | EA200101268A1 (fr) |
EE (1) | EE200100659A (fr) |
ES (1) | ES2234628T3 (fr) |
HR (1) | HRP20020008A2 (fr) |
HU (1) | HUP0202897A3 (fr) |
IL (1) | IL146094A0 (fr) |
IS (1) | IS6183A (fr) |
MA (1) | MA25530A1 (fr) |
MX (1) | MXPA01012483A (fr) |
NO (1) | NO20015045L (fr) |
NZ (1) | NZ514881A (fr) |
OA (1) | OA11959A (fr) |
PE (1) | PE20010211A1 (fr) |
PL (1) | PL352714A1 (fr) |
SK (1) | SK17302001A3 (fr) |
SV (1) | SV2002000096A (fr) |
UA (1) | UA71971C2 (fr) |
UY (1) | UY26190A1 (fr) |
WO (1) | WO2000075120A1 (fr) |
YU (1) | YU85601A (fr) |
ZA (1) | ZA200108291B (fr) |
Families Citing this family (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020150921A1 (en) * | 1996-02-09 | 2002-10-17 | Francis Barany | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
GEP20032896B (en) * | 1997-10-27 | 2003-02-25 | Agouron Pharma | 4-Aminothiazole Derivatives, Containing Them Pharmaceutical Compositions Inhibiting Cyclin-Dependent Kinases and Methods for Treatment |
US6262096B1 (en) | 1997-11-12 | 2001-07-17 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
US20040226056A1 (en) * | 1998-12-22 | 2004-11-11 | Myriad Genetics, Incorporated | Compositions and methods for treating neurological disorders and diseases |
US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
CZ302788B6 (cs) | 1999-04-15 | 2011-11-09 | Bristol-Myers Squibb Company | ´N-(2-Chlor-6-methylfenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolkarboxamid, jeho použití a farmaceutický prostredek s jeho obsahem |
DK1347971T3 (da) | 2000-12-21 | 2006-05-15 | Bristol Myers Squibb Co | Thiazolylinhibitorer af tyrosinkinaser fra Tec-familien |
US6756374B2 (en) | 2001-01-22 | 2004-06-29 | Hoffmann-La Roche Inc. | Diaminothiazoles having antiproliferative activity |
UA76977C2 (en) | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
EP1406632A4 (fr) * | 2001-06-08 | 2009-11-04 | Cytovia Inc | 3-aryl-5-aryl- 1,2,4 -oxadiazoles et leurs analogues, activateurs des caspases et inducteurs de l'apoptose, et leurs utilisations |
CA2474322A1 (fr) * | 2002-01-25 | 2003-07-31 | Kylix Pharmaceuticals B.V. | (thia-/oxa-/pyra) zoles substitues 4(hetero-) aryle pour inhibition de tie-2 |
US6818663B2 (en) * | 2002-05-17 | 2004-11-16 | Hoffmann-La Roches | Diaminothiazoles |
US8450302B2 (en) | 2002-08-02 | 2013-05-28 | Ab Science | 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors |
WO2004014903A1 (fr) | 2002-08-02 | 2004-02-19 | Ab Science | 2-(3-aminoaryl)amino-4-aryl-thiazoles et leur utilisation en tant que inhibiteurs de c-kit |
RU2337682C2 (ru) | 2002-11-01 | 2008-11-10 | Такеда Фармасьютикал Компани Лимитед | Средство для профилактики или лечения невропатии |
CA2516234A1 (fr) * | 2003-02-21 | 2004-09-02 | Pfizer Inc. | Derives d'amino-thiazole substitues par n-heterocyclyle en tant qu'inhibiteurs de la proteine kinase |
US7078419B2 (en) | 2003-03-10 | 2006-07-18 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
US6992096B2 (en) | 2003-04-11 | 2006-01-31 | Ptc Therapeutics, Inc. | 1,2,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
EP1618133A1 (fr) * | 2003-04-17 | 2006-01-25 | Pfizer Inc. | Structure cristalline de complexes du domaine kinase du recepteur du facteur de croissance endothelial vasculaire (vegfrkd) et de ligands et leurs procedes d'utilisation |
WO2005007091A2 (fr) * | 2003-07-07 | 2005-01-27 | Georgetown University | Inhibiteurs d'histone desacetylase et leurs procedes d'utilisation |
US8362017B2 (en) | 2003-08-29 | 2013-01-29 | Exelixis, Inc. | C-kit modulators and methods of use |
DK1680140T3 (da) * | 2003-10-16 | 2011-06-14 | Imclone Llc | Fibrolast-vækstfaktorreceptor-1-inhibitorer og fremgangsmåde til behandling deraf |
BRPI0506749A (pt) * | 2004-01-12 | 2007-05-22 | Applied Research Systems | derivados de tiazol e uso dos mesmos |
WO2005108370A1 (fr) * | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | Composés du benzène |
US7211576B2 (en) | 2004-04-20 | 2007-05-01 | Hoffmann-La Roche Inc. | Diaminothiazoles |
WO2006017216A1 (fr) * | 2004-07-12 | 2006-02-16 | Merck & Co., Inc. | Inhibiteurs de l'histone désacétylase |
CN101248054B (zh) | 2005-05-24 | 2012-05-09 | 默克雪兰诺有限公司 | 噻唑衍生物及其应用 |
AU2006251161B2 (en) | 2005-05-24 | 2011-06-30 | Merck Serono Sa | Thiazole derivatives and use thereof |
EP1945632B1 (fr) | 2005-11-08 | 2013-09-18 | Vertex Pharmaceuticals Incorporated | Modulateurs hétérocycliques de transporteurs à cassette liant l' atp |
AU2012244242B2 (en) * | 2005-12-28 | 2015-05-21 | Vertex Pharmaceuticals Incorporated | 1-(benzo [D] [1,3] dioxol-5-yl) -N- (phenyl) cyclopropane- carboxamide derivatives and related compounds as modulators of ATP-Binding Cassette transporters for the treatment of Cystic Fibrosis |
CA2635760C (fr) * | 2005-12-28 | 2014-07-15 | Vertex Pharmaceuticals Incorporated | Modulateurs de transporteurs a cassette liant l'atp |
WO2007084391A2 (fr) * | 2006-01-18 | 2007-07-26 | Amgen Inc. | Composes thiazole et procedes d'utilisation |
EP1991536A2 (fr) * | 2006-02-15 | 2008-11-19 | Abbott Laboratories | Nouveaux inhibiteurs d'acétyl-coa carboxylase (acc) et leur utilisation dans le traitement du diabète, de l'obésité et du syndrome métabolique |
CA2641734A1 (fr) * | 2006-02-15 | 2007-08-23 | Abbott Laboratories | Inhibiteurs de l'acetyl-coa carboxylase (acc) et leur utilisation dans les traitements du diabete, de l'obesite et d'un syndrome metabolique |
AU2007235524B2 (en) | 2006-03-30 | 2013-09-12 | Ptc Therapeutics, Inc. | Methods for the production of functional protein from DNA having a nonsense mutation and the treatment of disorders associated therewith |
MX2008015457A (es) | 2006-07-07 | 2009-01-16 | Boehringer Ingelheim Int | Derivados de heteroaril substituido en fenil y el uso de los mismos como agentes anti-tumorales. |
WO2008080134A2 (fr) | 2006-12-22 | 2008-07-03 | Rigel Pharmaceuticals, Inc. | Diaminothiazoles utiles en tant qu'inhibiteurs de axl |
NZ581259A (en) | 2007-05-09 | 2012-07-27 | Vertex Pharma | Modulators of cystic fibrosis transmembrane conductance regulator |
EP2176249A2 (fr) * | 2007-07-02 | 2010-04-21 | Boehringer Ingelheim International GmbH | Nouveaux composés chimiques |
CL2008001943A1 (es) | 2007-07-02 | 2009-09-11 | Boehringer Ingelheim Int | Compuestos derivados de fenil-triazol, inhibidores de enzimas de señales especificas que participan del control de la proliferacion celular; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar cancer, infecciones, enfermedades inflamatorias y autoinmunes. |
EP2173728A2 (fr) | 2007-07-17 | 2010-04-14 | Amgen Inc. | Modulateurs hétérocycliques de pkb |
AU2008276512A1 (en) * | 2007-07-17 | 2009-01-22 | Amgen Inc. | Thiadiazole modulators of PKB |
DK2639224T3 (en) | 2007-12-07 | 2016-10-17 | Vertex Pharma | A process for the preparation of cycloalkylcarboxiamido-pyridinbenzoesyrer |
NZ702159A (en) | 2007-12-07 | 2016-03-31 | Vertex Pharma | Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
US20110098296A1 (en) * | 2007-12-13 | 2011-04-28 | George Adjabeng | Thiazole And Oxazole Kinase Inhibitors |
NZ720282A (en) | 2008-02-28 | 2017-12-22 | Vertex Pharma | Heteroaryl derivatives as cftr modulators |
UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
EP2350052B1 (fr) | 2008-09-29 | 2014-08-13 | Boehringer Ingelheim International GmbH | Composés antiprolifératifs |
JP5858789B2 (ja) | 2009-01-16 | 2016-02-10 | ライジェル ファーマシューティカルズ, インコーポレイテッド | 転移性癌の予防、治療、または管理のための併用療法に用いるためのaxl阻害薬 |
US8637557B2 (en) | 2009-10-19 | 2014-01-28 | Taisho Pharmaceutical Co., Ltd | Aminothiazole derivative |
US8865703B2 (en) | 2010-03-26 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Pyridyltriazoles |
JP5871896B2 (ja) | 2010-03-26 | 2016-03-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | B−rafキナーゼインヒビター |
EP3150198B1 (fr) | 2010-04-07 | 2021-09-22 | Vertex Pharmaceuticals Incorporated | Compositions pharmaceutiques de l'acide 3- (6- (1- (2,2-difluorobenzo [d] [1,3] dioxol-5-yl) cyclopropanecarboxamido) -3-méthylpyriodin-2-yl) d'acide benzoïque et leur administration |
US8710055B2 (en) | 2010-12-21 | 2014-04-29 | Boehringer Ingelheim International Gmbh | Triazolylphenyl sulfonamides as serine/threonine kinase inhibitors |
EP2842955B1 (fr) * | 2012-04-26 | 2016-10-05 | ONO Pharmaceutical Co., Ltd. | Composé inhibiteur de trk |
WO2014129431A1 (fr) | 2013-02-19 | 2014-08-28 | 小野薬品工業株式会社 | COMPOSÉ INHIBANT Trk |
GB201309333D0 (en) * | 2013-05-23 | 2013-07-10 | Agency Science Tech & Res | Purine diones as WNT pathway modulators |
KR102280372B1 (ko) | 2013-11-12 | 2021-07-22 | 버텍스 파마슈티칼스 인코포레이티드 | Cftr 매개된 질환 치료용 약제학적 조성물의 제조 방법 |
CN112979575A (zh) | 2014-03-06 | 2021-06-18 | Ptc医疗公司 | 1,2,4-噁二唑苯甲酸的药物组合物和盐 |
HUE055423T2 (hu) | 2014-11-18 | 2021-11-29 | Vertex Pharma | Eljárás nagy áteresztõképességû tesztelõ nagy teljesítményû folyadék-kromatográfia elvégzésére |
WO2017075312A1 (fr) | 2015-10-30 | 2017-05-04 | Ptc Therapeutics, Inc. | Méthodes de traitement de l'épilepsie |
WO2018052967A1 (fr) * | 2016-09-13 | 2018-03-22 | Arbutus Biopharma, Inc. | Composés de chromane-8-carboxamide substitués et analogues de ceux-ci, et procédés les utilisant |
CN111233786B (zh) * | 2020-02-04 | 2021-11-26 | 中国人民解放军军事科学院军事医学研究院 | 含五元杂环的苯磺酰胺类化合物及其制备方法和用途 |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE273062C (de) | 1912-04-19 | 1914-04-20 | Deylen Sohn Firma | Vorrichtung zum Schränken von Plattenzündspänen |
AU558132B2 (en) | 1981-05-27 | 1987-01-22 | Labatt Brewing Co. Ltd. | Malt sterilisation with hydrogen peroxide |
EP0218728A1 (fr) | 1985-04-03 | 1987-04-22 | Yamanouchi Pharmaceutical Co. Ltd. | Derives d'phenylene |
DE69222637T2 (de) * | 1991-05-10 | 1998-02-26 | Rhone Poulenc Rorer Int | Bis mono- und bicyclische aryl- und heteroarylderivate mit inhibierender wirkung auf die egf und/oder pdgf-rezeptor tyrosinkinase |
AU670431B2 (en) | 1992-03-24 | 1996-07-18 | Merck Sharp & Dohme Limited | 3-ureido substituted benzodiazepin-2-ones having cholecystokinin and/or gastrin antagonistic activity and their use in therapy |
US5631156A (en) | 1994-06-21 | 1997-05-20 | The University Of Michigan | DNA encoding and 18 KD CDK6 inhibiting protein |
JPH10509708A (ja) | 1994-11-10 | 1998-09-22 | コア セラピューティクス,インコーポレイティド | プロテイン・キナーゼのインヒビターとして有用な医薬ピラゾール組成物 |
ES2151652T3 (es) | 1995-02-02 | 2001-01-01 | Smithkline Beecham Plc | Derivados de indol como antagonistas del receptor 5ht. |
US5710173A (en) | 1995-06-07 | 1998-01-20 | Sugen, Inc. | Thienyl compounds for inhibition of cell proliferative disorders |
AU6526896A (en) | 1995-07-22 | 1997-02-18 | Rhone-Poulenc Rorer Limited | Substituted aromatic compounds and their pharmaceutical use |
US5705499A (en) | 1995-10-06 | 1998-01-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | 8-arylalkyl- and 8-arylheteroalkyl-5,11-dihydro-6H-dipyrido 3,2-B:2',3'-e! 1!diazepines and their use in the treatment of HIV-1 infection |
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 |
AU2103097A (en) | 1996-03-15 | 1997-10-10 | Zeneca Limited | Cinnoline derivatives and use as medicine |
EP0816357B1 (fr) | 1996-06-27 | 2002-01-09 | Pfizer Inc. | Dérivés d'indazole substitués |
EA002113B1 (ru) | 1996-09-04 | 2001-12-24 | Пфайзер Инк. | Производные индазола и их использование в качестве ингибиторов фосфодиэстеразы (фдэ) типа iv и продуцирования фактора некроза опухоли (фно) |
ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
GEP20032896B (en) * | 1997-10-27 | 2003-02-25 | Agouron Pharma | 4-Aminothiazole Derivatives, Containing Them Pharmaceutical Compositions Inhibiting Cyclin-Dependent Kinases and Methods for Treatment |
AU754734B2 (en) | 1997-11-04 | 2002-11-21 | Pfizer Products Inc. | Indazole bioisostere replacement of catechol in therapeutically active compounds |
HUP0100330A3 (en) | 1997-11-04 | 2002-03-28 | Pfizer Prod Inc | Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors, compositions containing them and their use |
US6040321A (en) * | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
ES2237919T4 (es) * | 1998-06-18 | 2007-05-01 | Bristol-Myers Squibb Company | Inhibidores aminotiazol sustituidos con carbono de quinasas dependientes de ciclina. |
ES2211175T3 (es) | 1998-09-29 | 2004-07-01 | Wyeth Holdings Corporation | Inhibidores de proteinas de tipo tirosina quinasas a base de 3-cianoquinolinas sustituidas. |
-
2000
- 2000-02-06 UA UA2001129215A patent/UA71971C2/uk unknown
- 2000-06-02 UY UY26190A patent/UY26190A1/es not_active Application Discontinuation
- 2000-06-02 NZ NZ514881A patent/NZ514881A/en unknown
- 2000-06-02 EE EEP200100659A patent/EE200100659A/xx unknown
- 2000-06-02 JP JP2001501601A patent/JP2003501420A/ja not_active Abandoned
- 2000-06-02 SV SV2000000096A patent/SV2002000096A/es unknown
- 2000-06-02 MX MXPA01012483A patent/MXPA01012483A/es not_active Application Discontinuation
- 2000-06-02 CA CA002371158A patent/CA2371158A1/fr not_active Abandoned
- 2000-06-02 WO PCT/US2000/015188 patent/WO2000075120A1/fr not_active Application Discontinuation
- 2000-06-02 EA EA200101268A patent/EA200101268A1/ru unknown
- 2000-06-02 BR BR0011585-1A patent/BR0011585A/pt not_active IP Right Cessation
- 2000-06-02 YU YU85601A patent/YU85601A/sh unknown
- 2000-06-02 CZ CZ20014213A patent/CZ20014213A3/cs unknown
- 2000-06-02 HU HU0202897A patent/HUP0202897A3/hu unknown
- 2000-06-02 AU AU57254/00A patent/AU778071B2/en not_active Ceased
- 2000-06-02 SK SK1730-2001A patent/SK17302001A3/sk unknown
- 2000-06-02 AT AT00942660T patent/ATE288424T1/de not_active IP Right Cessation
- 2000-06-02 OA OA1200100321A patent/OA11959A/en unknown
- 2000-06-02 DE DE60017894T patent/DE60017894T2/de not_active Expired - Fee Related
- 2000-06-02 KR KR1020017015384A patent/KR20020015333A/ko not_active Application Discontinuation
- 2000-06-02 PE PE2000000553A patent/PE20010211A1/es not_active Application Discontinuation
- 2000-06-02 IL IL14609400A patent/IL146094A0/xx unknown
- 2000-06-02 ES ES00942660T patent/ES2234628T3/es not_active Expired - Lifetime
- 2000-06-02 AP APAP/P/2001/002341A patent/AP2001002341A0/en unknown
- 2000-06-02 PL PL00352714A patent/PL352714A1/xx not_active Application Discontinuation
- 2000-06-02 EP EP00942660A patent/EP1181283B1/fr not_active Expired - Lifetime
- 2000-06-02 CN CN00808440A patent/CN1359380A/zh active Pending
-
2001
- 2001-02-15 US US09/783,584 patent/US6620828B2/en not_active Expired - Fee Related
- 2001-10-09 ZA ZA200108291A patent/ZA200108291B/xx unknown
- 2001-10-17 NO NO20015045A patent/NO20015045L/no not_active Application Discontinuation
- 2001-11-29 IS IS6183A patent/IS6183A/is unknown
-
2002
- 2002-01-02 MA MA26465A patent/MA25530A1/fr unknown
- 2002-01-03 BG BG106276A patent/BG106276A/bg unknown
- 2002-01-04 HR HR20020008A patent/HRP20020008A2/hr not_active Application Discontinuation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
BG106276A (bg) | Диаминотиазоли и употребата им за инхибиране на протеин кинази | |
US6462069B2 (en) | Compounds, pharmaceutical compositions, and methods for inhibiting protein kinases | |
KR20200032154A (ko) | Nlrp 활성과 관련된 병태를 치료하기 위한 화합물 및 조성물 | |
EP1813606A1 (fr) | Composé amide | |
TW201930315A (zh) | 具抗b型肝炎病毒(hbv)活性之新穎高活性胺基-噻唑取代之吲哚-2-甲醯胺 | |
CN101790526A (zh) | 用作激酶抑制剂的5-杂芳基取代的吲唑化合物 | |
JP2011098984A (ja) | Cxc−ケモカインレセプターリガンドおよびcc−ケモカインレセプターリガンドとしてのイソチアゾールジオキシド | |
CN111263756A (zh) | Rad51抑制剂 | |
EP2107054A1 (fr) | Composés antiprolifératives et ses utilisations thérapeutiques | |
US20210115029A1 (en) | Pyridyl benzothiophenes as kinase inhibitors | |
CN102459251A (zh) | 作为白三烯a4水解酶的调节剂的具有两个稠合双环杂芳基部分的化合物 | |
CA2411928A1 (fr) | Composes pyrazole-thiazole, compositions pharmaceutiques les contenant, et leurs procedes d'utilisation pour inhiber les kinases cyclino-dependantes | |
TW202330537A (zh) | Wee1抑制劑及其製備和用途 | |
WO2023146513A1 (fr) | Composés et leurs procédés d'utilisation | |
BRPI0714535A2 (pt) | composto, pelo menos uma entidade quÍmica, composiÇço farmacÊutica, mÉtodo, formulaÇço farmcÊutica embalda e uso | |
NZ723972B2 (en) | Hepatitis b core protein allosteric modulators | |
NZ723972A (en) | Hepatitis b core protein allosteric modulators | |
NZ613087A (en) | Histone deacetylase inhibitors and compositions and methods of use thereof | |
NZ613087B2 (en) | Histone deacetylase inhibitors and compositions and methods of use thereof |