ES2533366T3 - Derivados azoicos de pirazolona biciclo-sustituidos, procedimiento de preparacion y utilización farmacéutica de los mismos - Google Patents
Derivados azoicos de pirazolona biciclo-sustituidos, procedimiento de preparacion y utilización farmacéutica de los mismos Download PDFInfo
- Publication number
- ES2533366T3 ES2533366T3 ES09703490.4T ES09703490T ES2533366T3 ES 2533366 T3 ES2533366 T3 ES 2533366T3 ES 09703490 T ES09703490 T ES 09703490T ES 2533366 T3 ES2533366 T3 ES 2533366T3
- Authority
- ES
- Spain
- Prior art keywords
- mixture
- methyl
- mmol
- hydroxy
- dihydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title description 11
- 238000002360 preparation method Methods 0.000 title description 11
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 207
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 150000001733 carboxylic acid esters Chemical class 0.000 claims abstract description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- MGQNMYSRDBFUIR-UHFFFAOYSA-N nitro cyanoformate Chemical compound [O-][N+](=O)OC(=O)C#N MGQNMYSRDBFUIR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 description 427
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 273
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 249
- 238000006243 chemical reaction Methods 0.000 description 169
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 154
- 238000004809 thin layer chromatography Methods 0.000 description 151
- 239000007858 starting material Substances 0.000 description 148
- 230000008034 disappearance Effects 0.000 description 138
- 239000011541 reaction mixture Substances 0.000 description 136
- -1 5'-Fluoro-2'-hydroxy-3 '- [N' - (1-indan-5-yl-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene) -hydrazino] -biphenyl Chemical group 0.000 description 135
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 134
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
- 238000004949 mass spectrometry Methods 0.000 description 132
- 239000007787 solid Substances 0.000 description 132
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 126
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 123
- 239000002253 acid Substances 0.000 description 119
- 239000012065 filter cake Substances 0.000 description 113
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 83
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 239000005457 ice water Substances 0.000 description 81
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- 238000010898 silica gel chromatography Methods 0.000 description 64
- 235000010288 sodium nitrite Nutrition 0.000 description 63
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 54
- 238000010992 reflux Methods 0.000 description 45
- 229920006395 saturated elastomer Polymers 0.000 description 44
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 42
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 40
- 235000017557 sodium bicarbonate Nutrition 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 238000001816 cooling Methods 0.000 description 38
- 108010041111 Thrombopoietin Proteins 0.000 description 37
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
- 102000036693 Thrombopoietin Human genes 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 33
- 239000000284 extract Substances 0.000 description 31
- 239000000706 filtrate Substances 0.000 description 31
- 206010033799 Paralysis Diseases 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 239000002274 desiccant Substances 0.000 description 21
- 239000010410 layer Substances 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- HLSKTUANRGHHGI-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-5-yl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(CCC2)C2=C1 HLSKTUANRGHHGI-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- AJNGYKJVXWONGA-UHFFFAOYSA-N 5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(CCCC2)C2=C1 AJNGYKJVXWONGA-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000002156 mixing Methods 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 239000011877 solvent mixture Substances 0.000 description 14
- 239000012043 crude product Substances 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 150000004702 methyl esters Chemical class 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- JKHCSEPRRUKNJR-UHFFFAOYSA-N 2-(2-methoxy-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1B1OC(C)(C)C(C)(C)O1 JKHCSEPRRUKNJR-UHFFFAOYSA-N 0.000 description 10
- QWDNBBMMGCAVTN-UHFFFAOYSA-N 3-(3-amino-2-hydroxy-5-methylphenyl)benzoic acid;hydrochloride Chemical compound Cl.CC1=CC(N)=C(O)C(C=2C=C(C=CC=2)C(O)=O)=C1 QWDNBBMMGCAVTN-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 10
- DVNVHYZCRZPUIM-UHFFFAOYSA-N 2-(3,3-dimethyl-1,2-dihydroinden-5-yl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(CCC2(C)C)C2=C1 DVNVHYZCRZPUIM-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- LIIUUBUEBVCYDA-UHFFFAOYSA-N 3-(3-amino-2-hydroxyphenyl)benzoic acid;hydrobromide Chemical compound Br.NC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O LIIUUBUEBVCYDA-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
- JUTDHLQZZORZJS-UHFFFAOYSA-N 5-methyl-2-(3-methyl-2,3-dihydro-1h-inden-5-yl)-4h-pyrazol-3-one Chemical compound C1=C2C(C)CCC2=CC=C1N1N=C(C)CC1=O JUTDHLQZZORZJS-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 7
- ZKFZFBOAGWUBQI-UHFFFAOYSA-N 3-(3-amino-5-fluoro-2-hydroxyphenyl)benzoic acid Chemical compound NC1=CC(F)=CC(C=2C=C(C=CC=2)C(O)=O)=C1O ZKFZFBOAGWUBQI-UHFFFAOYSA-N 0.000 description 6
- CEAZQXRZBQTIIW-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)furan-2-carboxylic acid;hydrobromide Chemical compound Br.NC1=CC=CC(C=2OC(=CC=2)C(O)=O)=C1O CEAZQXRZBQTIIW-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 210000003593 megakaryocyte Anatomy 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 6
- YAYBLVOBUIXMQY-UHFFFAOYSA-N 1-bromo-2-methoxy-3-nitrobenzene Chemical compound COC1=C(Br)C=CC=C1[N+]([O-])=O YAYBLVOBUIXMQY-UHFFFAOYSA-N 0.000 description 5
- LAADWVXCBDSARD-UHFFFAOYSA-N 2-(2,2-dimethyl-1,3-dihydroinden-5-yl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(CC(C)(C)C2)C2=C1 LAADWVXCBDSARD-UHFFFAOYSA-N 0.000 description 5
- SWSCKLXUQFVPPN-UHFFFAOYSA-N 2-amino-6-[3-(2H-tetrazol-5-yl)phenyl]phenol Chemical compound NC1=CC=CC(C=2C=C(C=CC=2)C=2NN=NN=2)=C1O SWSCKLXUQFVPPN-UHFFFAOYSA-N 0.000 description 5
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 5
- SSJHCVPKVRRXNR-UHFFFAOYSA-N 5-methyl-2-(1,1,3,3-tetramethyl-2h-inden-5-yl)-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C2C(C)(C)CC(C)(C)C2=C1 SSJHCVPKVRRXNR-UHFFFAOYSA-N 0.000 description 5
- SEQHEDQNODAFIU-UHFFFAOYSA-N 6-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2CCC(=O)C2=C1 SEQHEDQNODAFIU-UHFFFAOYSA-N 0.000 description 5
- 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 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 150000003254 radicals Chemical group 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 206010043554 thrombocytopenia Diseases 0.000 description 5
- CMLYAHYWAINDLT-UHFFFAOYSA-N 1-bromo-2-methoxy-5-methyl-3-nitrobenzene Chemical compound COC1=C(Br)C=C(C)C=C1[N+]([O-])=O CMLYAHYWAINDLT-UHFFFAOYSA-N 0.000 description 4
- KBOGEGUAFGNMNM-UHFFFAOYSA-N 2-(2,3-dihydro-1-benzofuran-5-yl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(OCC2)C2=C1 KBOGEGUAFGNMNM-UHFFFAOYSA-N 0.000 description 4
- CLSFJNMZEMHJON-UHFFFAOYSA-N 2-(3-ethyl-2,3-dihydro-1h-inden-5-yl)-5-methyl-4h-pyrazol-3-one Chemical compound C1=C2C(CC)CCC2=CC=C1N1N=C(C)CC1=O CLSFJNMZEMHJON-UHFFFAOYSA-N 0.000 description 4
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 4
- BCUGMTSFLCYGEC-UHFFFAOYSA-N 5-(2-methoxy-3-nitrophenyl)furan-2-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C(O)=O)O1 BCUGMTSFLCYGEC-UHFFFAOYSA-N 0.000 description 4
- UCTQSSOHKXIBKJ-UHFFFAOYSA-N 5-(3-amino-2-hydroxy-5-methylphenyl)thiophene-2-carboxylic acid;hydrobromide Chemical compound Br.CC1=CC(N)=C(O)C(C=2SC(=CC=2)C(O)=O)=C1 UCTQSSOHKXIBKJ-UHFFFAOYSA-N 0.000 description 4
- YPMPBMCHAWUZCJ-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)thiophene-2-carboxylic acid;hydrobromide Chemical compound Br.NC1=CC=CC(C=2SC(=CC=2)C(O)=O)=C1O YPMPBMCHAWUZCJ-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 239000004317 sodium nitrate Substances 0.000 description 4
- 235000010344 sodium nitrate Nutrition 0.000 description 4
- 238000012453 sprague-dawley rat model Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
- RMUJVOPHLHFICQ-UHFFFAOYSA-N 1-bromo-5-fluoro-2-methoxy-3-nitrobenzene Chemical compound COC1=C(Br)C=C(F)C=C1[N+]([O-])=O RMUJVOPHLHFICQ-UHFFFAOYSA-N 0.000 description 3
- BBFDGMDENAEMKF-UHFFFAOYSA-N 2,2,2-trichloro-1-(1h-pyrrol-2-yl)ethanone Chemical compound ClC(Cl)(Cl)C(=O)C1=CC=CN1 BBFDGMDENAEMKF-UHFFFAOYSA-N 0.000 description 3
- PAVKKFAIAQPCRG-UHFFFAOYSA-N 2,2,2-trichloro-1-(4-iodo-1h-pyrrol-2-yl)ethanone Chemical compound ClC(Cl)(Cl)C(=O)C1=CC(I)=CN1 PAVKKFAIAQPCRG-UHFFFAOYSA-N 0.000 description 3
- BNXIZYJGSFWKCI-UHFFFAOYSA-N 2-(3-amino-2-methoxyphenyl)-5-methyl-1,3-thiazole-4-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=NC(C(O)=O)=C(C)S1 BNXIZYJGSFWKCI-UHFFFAOYSA-N 0.000 description 3
- FWQOTUMLLIVQGG-UHFFFAOYSA-N 2-[3-(2h-tetrazol-5-yl)phenyl]phenol Chemical compound OC1=CC=CC=C1C1=CC=CC(C=2NN=NN=2)=C1 FWQOTUMLLIVQGG-UHFFFAOYSA-N 0.000 description 3
- DFHGOCSWFGXYSQ-UHFFFAOYSA-N 2-bromo-4-fluoro-6-nitrophenol Chemical compound OC1=C(Br)C=C(F)C=C1[N+]([O-])=O DFHGOCSWFGXYSQ-UHFFFAOYSA-N 0.000 description 3
- VEJSIOPQKQXJAT-UHFFFAOYSA-N 2-bromo-6-nitrophenol Chemical compound OC1=C(Br)C=CC=C1[N+]([O-])=O VEJSIOPQKQXJAT-UHFFFAOYSA-N 0.000 description 3
- CFGQZVOVFIZRMN-UHFFFAOYSA-N 2-methylfuran-3-carboxylic acid Chemical compound CC=1OC=CC=1C(O)=O CFGQZVOVFIZRMN-UHFFFAOYSA-N 0.000 description 3
- ZUUFSSLIAUDWNB-UHFFFAOYSA-N 2-nitro-6-[3-(2h-tetrazol-5-yl)phenyl]phenol Chemical compound C1=CC=C([N+]([O-])=O)C(O)=C1C1=CC=CC(C=2NN=NN=2)=C1 ZUUFSSLIAUDWNB-UHFFFAOYSA-N 0.000 description 3
- ABMPSIRCVCUHLO-UHFFFAOYSA-N 20039-91-2 Chemical compound CC1=CC(Br)=C(O)C([N+]([O-])=O)=C1 ABMPSIRCVCUHLO-UHFFFAOYSA-N 0.000 description 3
- AAPGMCIBKOSNAL-UHFFFAOYSA-N 3-(2-methoxy-3-nitrophenyl)benzoic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=CC(C(O)=O)=C1 AAPGMCIBKOSNAL-UHFFFAOYSA-N 0.000 description 3
- XTGXSESGSWUDQN-UHFFFAOYSA-N 3-(3-amino-2-methoxyphenyl)benzoic acid Chemical compound COC1=C(N)C=CC=C1C1=CC=CC(C(O)=O)=C1 XTGXSESGSWUDQN-UHFFFAOYSA-N 0.000 description 3
- BISOXGBVBJUYSO-UHFFFAOYSA-N 3-(3-amino-5-fluoro-2-hydroxyphenyl)benzoic acid;hydrobromide Chemical compound Br.NC1=CC(F)=CC(C=2C=C(C=CC=2)C(O)=O)=C1O BISOXGBVBJUYSO-UHFFFAOYSA-N 0.000 description 3
- RGUUEAHVNUOJSC-UHFFFAOYSA-N 3-(5-fluoro-2-hydroxy-3-nitrophenyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C(=C(C=C(F)C=2)[N+]([O-])=O)O)=C1 RGUUEAHVNUOJSC-UHFFFAOYSA-N 0.000 description 3
- HNZIVMYTHZWCDU-UHFFFAOYSA-N 3-(5-fluoro-2-methoxy-3-nitrophenyl)benzoic acid Chemical compound C1=C(F)C=C([N+]([O-])=O)C(OC)=C1C1=CC=CC(C(O)=O)=C1 HNZIVMYTHZWCDU-UHFFFAOYSA-N 0.000 description 3
- RLCDWORGDIRBQU-UHFFFAOYSA-N 3-[4-(4,5-dihydro-1h-imidazol-2-yl)phenyl]-2-methoxyaniline Chemical compound COC1=C(N)C=CC=C1C1=CC=C(C=2NCCN=2)C=C1 RLCDWORGDIRBQU-UHFFFAOYSA-N 0.000 description 3
- DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 3
- XNLWJFYYOIRPIO-UHFFFAOYSA-N 3-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1 XNLWJFYYOIRPIO-UHFFFAOYSA-N 0.000 description 3
- LFDYHUQWSVZAHJ-UHFFFAOYSA-N 4-(2-methoxy-3-nitrophenyl)-1h-pyrrole-2-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CNC(C(O)=O)=C1 LFDYHUQWSVZAHJ-UHFFFAOYSA-N 0.000 description 3
- RVWVOHPOLFDXJU-UHFFFAOYSA-N 4-(2-methoxy-3-nitrophenyl)benzaldehyde Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C=O)C=C1 RVWVOHPOLFDXJU-UHFFFAOYSA-N 0.000 description 3
- MRSRXXMBZXDZMX-UHFFFAOYSA-N 4-(2-methoxy-3-nitrophenyl)furan-2-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=COC(C(O)=O)=C1 MRSRXXMBZXDZMX-UHFFFAOYSA-N 0.000 description 3
- XOCJQNXOSLYJNT-UHFFFAOYSA-N 4-(2-methoxy-3-nitrophenyl)thiophene-2-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CSC(C(O)=O)=C1 XOCJQNXOSLYJNT-UHFFFAOYSA-N 0.000 description 3
- FVWMLPLQQVWWBZ-UHFFFAOYSA-N 4-(3-amino-2-hydroxyphenyl)-1h-pyrrole-2-carboxylic acid Chemical compound NC1=CC=CC(C=2C=C(NC=2)C(O)=O)=C1O FVWMLPLQQVWWBZ-UHFFFAOYSA-N 0.000 description 3
- YKUNBQNIMDXCEX-UHFFFAOYSA-N 4-(3-amino-2-hydroxyphenyl)furan-2-carboxylic acid;hydrobromide Chemical compound Br.NC1=CC=CC(C=2C=C(OC=2)C(O)=O)=C1O YKUNBQNIMDXCEX-UHFFFAOYSA-N 0.000 description 3
- ZIWZDCCQIOCJBA-UHFFFAOYSA-N 4-(3-amino-2-methoxyphenyl)-1h-pyrrole-2-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=CNC(C(O)=O)=C1 ZIWZDCCQIOCJBA-UHFFFAOYSA-N 0.000 description 3
- SDTAVYCGOUXFPQ-UHFFFAOYSA-N 4-(3-amino-2-methoxyphenyl)furan-2-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=COC(C(O)=O)=C1 SDTAVYCGOUXFPQ-UHFFFAOYSA-N 0.000 description 3
- GMHHTGYHERDNLO-UHFFFAOYSA-N 4-bromobicyclo[4.2.0]octa-1(6),2,4-triene Chemical compound BrC1=CC=C2CCC2=C1 GMHHTGYHERDNLO-UHFFFAOYSA-N 0.000 description 3
- DXKYHAPIBYYLJR-UHFFFAOYSA-N 4-ethoxycarbonyl-3,5-dimethyl-1h-pyrrole-2-carboxylic acid Chemical compound CCOC(=O)C1=C(C)NC(C(O)=O)=C1C DXKYHAPIBYYLJR-UHFFFAOYSA-N 0.000 description 3
- NWRRQZWNNDQYLF-UHFFFAOYSA-N 5-(2-methoxy-3-nitrophenyl)thiophene-2-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C(O)=O)S1 NWRRQZWNNDQYLF-UHFFFAOYSA-N 0.000 description 3
- OPSVDOMVZGALQW-UHFFFAOYSA-N 5-(2-methoxy-5-methyl-3-nitrophenyl)furan-2-carboxylic acid Chemical compound C1=C(C)C=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C(O)=O)O1 OPSVDOMVZGALQW-UHFFFAOYSA-N 0.000 description 3
- XSUHROKKIPXFHG-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)-2-methylfuran-3-carboxylic acid;hydrobromide Chemical compound Br.OC(=O)C1=C(C)OC(C=2C(=C(N)C=CC=2)O)=C1 XSUHROKKIPXFHG-UHFFFAOYSA-N 0.000 description 3
- HFVWWGLPSFPTQE-UHFFFAOYSA-N 5-(3-amino-2-methoxy-5-methylphenyl)thiophene-2-carboxylic acid Chemical compound COC1=C(N)C=C(C)C=C1C1=CC=C(C(O)=O)S1 HFVWWGLPSFPTQE-UHFFFAOYSA-N 0.000 description 3
- SLHFGYLLIGICCB-UHFFFAOYSA-N 5-(3-amino-2-methoxyphenyl)-2-methylfuran-3-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=CC(C(O)=O)=C(C)O1 SLHFGYLLIGICCB-UHFFFAOYSA-N 0.000 description 3
- HXUVTLQIIPFDRS-UHFFFAOYSA-N 5-(3-amino-2-methoxyphenyl)furan-2-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=CC=C(C(O)=O)O1 HXUVTLQIIPFDRS-UHFFFAOYSA-N 0.000 description 3
- ZKMLKVADVLNANN-UHFFFAOYSA-N 5-(3-amino-2-methoxyphenyl)thiophene-2-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=CC=C(C(O)=O)S1 ZKMLKVADVLNANN-UHFFFAOYSA-N 0.000 description 3
- UVKPUDRFBHSFJH-UHFFFAOYSA-N 5-(3-bromophenyl)-2h-tetrazole Chemical compound BrC1=CC=CC(C2=NNN=N2)=C1 UVKPUDRFBHSFJH-UHFFFAOYSA-N 0.000 description 3
- UYPLLXDKEYUALO-UHFFFAOYSA-N 5-[3-(2-methoxyphenyl)phenyl]-2h-tetrazole Chemical compound COC1=CC=CC=C1C1=CC=CC(C=2NN=NN=2)=C1 UYPLLXDKEYUALO-UHFFFAOYSA-N 0.000 description 3
- JCJBXUASIJDKNN-UHFFFAOYSA-N 5-bromo-1,1,3,3-tetramethyl-2h-indene Chemical compound BrC1=CC=C2C(C)(C)CC(C)(C)C2=C1 JCJBXUASIJDKNN-UHFFFAOYSA-N 0.000 description 3
- WLVAHLRWOFCOTC-UHFFFAOYSA-N 5-bromo-2,2-dimethyl-1,3-dihydroindene Chemical compound C1=C(Br)C=C2CC(C)(C)CC2=C1 WLVAHLRWOFCOTC-UHFFFAOYSA-N 0.000 description 3
- MVIGYOCYIUJCGE-UHFFFAOYSA-N 5-bromo-3,3-dimethyl-2h-inden-1-one Chemical compound C1=C(Br)C=C2C(C)(C)CC(=O)C2=C1 MVIGYOCYIUJCGE-UHFFFAOYSA-N 0.000 description 3
- OEOFJZMGAKVHEP-UHFFFAOYSA-N 5-bromo-3-ethylidene-1,2-dihydroindene Chemical compound C1=C(Br)C=C2C(=CC)CCC2=C1 OEOFJZMGAKVHEP-UHFFFAOYSA-N 0.000 description 3
- ZFDZBOGSBHTCJC-UHFFFAOYSA-N 5-bromo-3-methylidene-1,2-dihydroindene Chemical compound BrC1=CC=C2CCC(=C)C2=C1 ZFDZBOGSBHTCJC-UHFFFAOYSA-N 0.000 description 3
- ITEWLUAKUOBQHQ-UHFFFAOYSA-N 6-bromo-1-ethyl-2,3-dihydro-1h-indene Chemical compound C1=C(Br)C=C2C(CC)CCC2=C1 ITEWLUAKUOBQHQ-UHFFFAOYSA-N 0.000 description 3
- NZNSJAFTXNTNAA-UHFFFAOYSA-N 6-bromo-1-methyl-2,3-dihydro-1h-indene Chemical compound C1=C(Br)C=C2C(C)CCC2=C1 NZNSJAFTXNTNAA-UHFFFAOYSA-N 0.000 description 3
- ILFZPAUIJLEEAO-UHFFFAOYSA-N 6-bromo-2,2-dimethyl-3h-inden-1-one Chemical compound C1=C(Br)C=C2C(=O)C(C)(C)CC2=C1 ILFZPAUIJLEEAO-UHFFFAOYSA-N 0.000 description 3
- SGALMGILCDDTQI-UHFFFAOYSA-N CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 SGALMGILCDDTQI-UHFFFAOYSA-N 0.000 description 3
- ZNYRJGIYMOGLGW-UHFFFAOYSA-N CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 Chemical compound CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 ZNYRJGIYMOGLGW-UHFFFAOYSA-N 0.000 description 3
- QWLPNUKHXURTGQ-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=C1)=CC=C1C1=NCCN1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=C1)=CC=C1C1=NCCN1 QWLPNUKHXURTGQ-UHFFFAOYSA-N 0.000 description 3
- XIOBVYSCEDOTEO-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 XIOBVYSCEDOTEO-UHFFFAOYSA-N 0.000 description 3
- ZYDVBBAKIDZLOC-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 ZYDVBBAKIDZLOC-UHFFFAOYSA-N 0.000 description 3
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- XDXWLKQMMKQXPV-QYQHSDTDSA-N eltrombopag Chemical compound CC1=NN(C=2C=C(C)C(C)=CC=2)C(=O)\C1=N/NC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 XDXWLKQMMKQXPV-QYQHSDTDSA-N 0.000 description 3
- 229960001069 eltrombopag Drugs 0.000 description 3
- RIKHOVQNNXYUPH-UHFFFAOYSA-N ethyl 5-(3-amino-2-methoxyphenyl)-1,2,4-trimethylpyrrole-3-carboxylate Chemical compound CN1C(C)=C(C(=O)OCC)C(C)=C1C1=CC=CC(N)=C1OC RIKHOVQNNXYUPH-UHFFFAOYSA-N 0.000 description 3
- SEGVQMWMZJCWHD-UHFFFAOYSA-N ethyl 5-iodo-1,2,4-trimethylpyrrole-3-carboxylate Chemical compound CCOC(=O)C=1C(C)=C(I)N(C)C=1C SEGVQMWMZJCWHD-UHFFFAOYSA-N 0.000 description 3
- XUMRTTYVSXENOU-UHFFFAOYSA-N methyl 4-iodo-1-(4-methylphenyl)sulfonylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(I)=CN1S(=O)(=O)C1=CC=C(C)C=C1 XUMRTTYVSXENOU-UHFFFAOYSA-N 0.000 description 3
- HQEFZABRNVWGBR-UHFFFAOYSA-N methyl 5-bromo-2-methylfuran-3-carboxylate Chemical compound COC(=O)C=1C=C(Br)OC=1C HQEFZABRNVWGBR-UHFFFAOYSA-N 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
- TZQWYTNGPYDSEM-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-ylhydrazine Chemical compound NNC1=CC=C2CCCC2=C1 TZQWYTNGPYDSEM-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- SGBNUABVXDJREL-UHFFFAOYSA-N 2-(3-amino-2-hydroxyphenyl)-5-methyl-1,3-thiazole-4-carboxylic acid hydrobromide Chemical compound Br.OC(=O)C1=C(C)SC(C=2C(=C(N)C=CC=2)O)=N1 SGBNUABVXDJREL-UHFFFAOYSA-N 0.000 description 2
- RWGNRARLAGZJFZ-UHFFFAOYSA-N 2-amino-6-[4-(4,5-dihydroimidazol-1-yl)phenyl]phenol Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)N2C=NCC2)=C1O RWGNRARLAGZJFZ-UHFFFAOYSA-N 0.000 description 2
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical class OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 2
- DJXZDKWFOFTMRO-UHFFFAOYSA-N 2-fluoro-3-(2-hydroxyphenyl)benzoic acid Chemical compound FC1=C(C=CC=C1C(=O)O)C1=C(C=CC=C1)O DJXZDKWFOFTMRO-UHFFFAOYSA-N 0.000 description 2
- PDRLOUFXSDADGH-UHFFFAOYSA-N 3-(2-hydroxy-5-methyl-3-nitrophenyl)benzoic acid Chemical compound [O-][N+](=O)C1=CC(C)=CC(C=2C=C(C=CC=2)C(O)=O)=C1O PDRLOUFXSDADGH-UHFFFAOYSA-N 0.000 description 2
- HHPDYYCDILLKCD-UHFFFAOYSA-N 3-(3-amino-2-hydroxyphenyl)benzoic acid;hydrochloride Chemical compound Cl.NC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O HHPDYYCDILLKCD-UHFFFAOYSA-N 0.000 description 2
- UZBGSJZFBUOJNE-UHFFFAOYSA-N 3-bromofuran-2-carboxylic acid Chemical compound OC(=O)C=1OC=CC=1Br UZBGSJZFBUOJNE-UHFFFAOYSA-N 0.000 description 2
- UBQYAPFIXRYXKZ-UHFFFAOYSA-N 4-(3-amino-2-hydroxyphenyl)thiophene-2-carboxylic acid;hydrobromide Chemical compound Br.NC1=CC=CC(C=2C=C(SC=2)C(O)=O)=C1O UBQYAPFIXRYXKZ-UHFFFAOYSA-N 0.000 description 2
- CQTMNFPHXCCOLC-UHFFFAOYSA-N 4-(3-amino-2-methoxyphenyl)thiophene-2-carboxylic acid Chemical compound COC1=C(N)C=CC=C1C1=CSC(C(O)=O)=C1 CQTMNFPHXCCOLC-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
- QALYBHRYGIXHOF-UHFFFAOYSA-N 4-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=CO1 QALYBHRYGIXHOF-UHFFFAOYSA-N 0.000 description 2
- DDESOTPPLFAWEJ-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalen-2-ylhydrazine Chemical compound C1CCCC2=CC(NN)=CC=C21 DDESOTPPLFAWEJ-UHFFFAOYSA-N 0.000 description 2
- KCMXDUNFVPYWDN-UHFFFAOYSA-N 5-(2-methoxy-3-nitrophenyl)-2-methylfuran-3-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC(C(O)=O)=C(C)O1 KCMXDUNFVPYWDN-UHFFFAOYSA-N 0.000 description 2
- ZIHFBTIPDWMLKI-UHFFFAOYSA-N 5-(2-methoxy-5-methyl-3-nitrophenyl)thiophene-2-carboxylic acid Chemical compound C1=C(C)C=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C(O)=O)S1 ZIHFBTIPDWMLKI-UHFFFAOYSA-N 0.000 description 2
- XHELHVCZTPRSGF-UHFFFAOYSA-N 5-(2-methoxy-5-methylphenyl)-1-nitrocyclohexa-2,4-diene-1-carboxylic acid Chemical compound COC1=CC=C(C)C=C1C1=CC=CC([N+]([O-])=O)(C(O)=O)C1 XHELHVCZTPRSGF-UHFFFAOYSA-N 0.000 description 2
- FDFORHCNPUBQTA-UHFFFAOYSA-N 5-(3-amino-2-hydroxy-5-methylphenyl)furan-2-carboxylic acid;hydrobromide Chemical compound Br.CC1=CC(N)=C(O)C(C=2OC(=CC=2)C(O)=O)=C1 FDFORHCNPUBQTA-UHFFFAOYSA-N 0.000 description 2
- GMBJMBHFEPCHRN-UHFFFAOYSA-N 5-(3-amino-2-methoxy-5-methylphenyl)furan-2-carboxylic acid Chemical compound COC1=C(N)C=C(C)C=C1C1=CC=C(C(O)=O)O1 GMBJMBHFEPCHRN-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- RNRAWOMVIZHUQC-UHFFFAOYSA-N C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 Chemical compound C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 RNRAWOMVIZHUQC-UHFFFAOYSA-N 0.000 description 2
- VGRPINLOMRZVAY-UHFFFAOYSA-N C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 VGRPINLOMRZVAY-UHFFFAOYSA-N 0.000 description 2
- WISYHTHFKZUFHN-UHFFFAOYSA-N C1=C2C(CC)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound C1=C2C(CC)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 WISYHTHFKZUFHN-UHFFFAOYSA-N 0.000 description 2
- KGUOBRICGYWBTL-UHFFFAOYSA-N C1=C2C(CC)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound C1=C2C(CC)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 KGUOBRICGYWBTL-UHFFFAOYSA-N 0.000 description 2
- FROOUFQIWFLLNX-UHFFFAOYSA-N CC1=NN(C(=O)C1=NNc1cc(C)cc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCc2c1 Chemical compound CC1=NN(C(=O)C1=NNc1cc(C)cc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCc2c1 FROOUFQIWFLLNX-UHFFFAOYSA-N 0.000 description 2
- RXCAOGWWRIFTNM-UHFFFAOYSA-N CC1=NN(C(=O)C1=NNc1cccc(-c2cccc(c2)-c2nnn[nH]2)c1O)c1ccc2CCc2c1 Chemical compound CC1=NN(C(=O)C1=NNc1cccc(-c2cccc(c2)-c2nnn[nH]2)c1O)c1ccc2CCc2c1 RXCAOGWWRIFTNM-UHFFFAOYSA-N 0.000 description 2
- NIWDNYOLPCODOI-UHFFFAOYSA-N CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 NIWDNYOLPCODOI-UHFFFAOYSA-N 0.000 description 2
- WQKNZVVIOWVGLX-UHFFFAOYSA-N CC1=NN(C=2C=C3CC(C)(C)CC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CC(C)(C)CC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 WQKNZVVIOWVGLX-UHFFFAOYSA-N 0.000 description 2
- ZJFGSTVAUPOMRT-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 ZJFGSTVAUPOMRT-UHFFFAOYSA-N 0.000 description 2
- ZPPFAHGBHPWTAR-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CNC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CNC(C(O)=O)=C1 ZPPFAHGBHPWTAR-UHFFFAOYSA-N 0.000 description 2
- LXZVTUDQBDJDMN-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=COC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=COC(C(O)=O)=C1 LXZVTUDQBDJDMN-UHFFFAOYSA-N 0.000 description 2
- LKNGCCJIZCKNIQ-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 LKNGCCJIZCKNIQ-UHFFFAOYSA-N 0.000 description 2
- IUMBFXVORWTHRY-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CSC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CSC(C(O)=O)=C1 IUMBFXVORWTHRY-UHFFFAOYSA-N 0.000 description 2
- GHMVPZMJVJXPCY-UHFFFAOYSA-N CC1=NN(C=2C=C3CCOC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCOC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 GHMVPZMJVJXPCY-UHFFFAOYSA-N 0.000 description 2
- WDCBDHCATROYFF-UHFFFAOYSA-N CC1=NN(C=2C=C3CCOC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCOC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 WDCBDHCATROYFF-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 101000799466 Homo sapiens Thrombopoietin receptor Proteins 0.000 description 2
- 101000694103 Homo sapiens Thyroid peroxidase Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 102100034196 Thrombopoietin receptor Human genes 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000000409 cytokine receptor agonist Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- JYGAZRRCFNQYGK-UHFFFAOYSA-N ethyl 5-(3-amino-2-hydroxyphenyl)-1,2,4-trimethylpyrrole-3-carboxylate Chemical compound CN1C(C)=C(C(=O)OCC)C(C)=C1C1=CC=CC(N)=C1O JYGAZRRCFNQYGK-UHFFFAOYSA-N 0.000 description 2
- JDALSIJMOYCBTO-UHFFFAOYSA-N ethyl 5-iodo-2,4-dimethyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(I)=C1C JDALSIJMOYCBTO-UHFFFAOYSA-N 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 2
- 102000053400 human TPO Human genes 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- UVGKQVVHSVASLH-UHFFFAOYSA-N methyl 4-(2-methoxy-3-nitrophenyl)-1-(4-methylphenyl)sulfonylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(C=2C(=C(C=CC=2)[N+]([O-])=O)OC)=CN1S(=O)(=O)C1=CC=C(C)C=C1 UVGKQVVHSVASLH-UHFFFAOYSA-N 0.000 description 2
- KRNGDJYQOKCQCD-UHFFFAOYSA-N methyl 4-iodo-1h-pyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(I)=CN1 KRNGDJYQOKCQCD-UHFFFAOYSA-N 0.000 description 2
- RFVWMXPMHIHIIB-UHFFFAOYSA-N methyl 5-(3-amino-2-hydroxyphenyl)furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1C1=CC=CC(N)=C1O RFVWMXPMHIHIIB-UHFFFAOYSA-N 0.000 description 2
- FOAPZKJLLVICGW-UHFFFAOYSA-N methyl 5-(3-amino-2-methoxyphenyl)furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1C1=CC=CC(N)=C1OC FOAPZKJLLVICGW-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- SPFPGSYLNIIQMG-UHFFFAOYSA-N (carboxyamino)carbamic acid Chemical compound OC(=O)NNC(O)=O SPFPGSYLNIIQMG-UHFFFAOYSA-N 0.000 description 1
- ZQJODLRWWIIHDM-UHFFFAOYSA-N 1,2-dimethylpyrrole-3-carboxylic acid Chemical compound CC1=C(C(O)=O)C=CN1C ZQJODLRWWIIHDM-UHFFFAOYSA-N 0.000 description 1
- RGGLEJFUEMKQSH-UHFFFAOYSA-N 1,4-benzodiazepin-2-one Chemical class O=C1C=NC=C2C=CC=CC2=N1 RGGLEJFUEMKQSH-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- VVDNZFHIZRVWOX-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(2,2,2-trichloroethoxycarbonylamino)carbamate Chemical compound ClC(Cl)(Cl)COC(=O)NNC(=O)OCC(Cl)(Cl)Cl VVDNZFHIZRVWOX-UHFFFAOYSA-N 0.000 description 1
- LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 1
- DYIFXZWICBFBHF-UHFFFAOYSA-N 2,4,5-trimethyl-1h-pyrrole-3-carboxylic acid Chemical compound CC=1NC(C)=C(C(O)=O)C=1C DYIFXZWICBFBHF-UHFFFAOYSA-N 0.000 description 1
- PYHQGYGKYFNCMW-UHFFFAOYSA-N 2-(1,3-thiazol-2-yl)benzamide Chemical class NC(=O)C1=CC=CC=C1C1=NC=CS1 PYHQGYGKYFNCMW-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- YUEUMALVUUUPKQ-UHFFFAOYSA-N 2-(2-methoxy-3-nitrophenyl)-5-methyl-1,3-thiazole-4-carboxylic acid Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=NC(C(O)=O)=C(C)S1 YUEUMALVUUUPKQ-UHFFFAOYSA-N 0.000 description 1
- HEHOGIWCONBSMS-UHFFFAOYSA-N 2-(2-methoxy-5-methyl-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C1=C(C)C=C([N+]([O-])=O)C(OC)=C1B1OC(C)(C)C(C)(C)O1 HEHOGIWCONBSMS-UHFFFAOYSA-N 0.000 description 1
- SUGJWGQOVBOKGL-UHFFFAOYSA-N 2-(2-methoxy-5-methyl-3-nitrophenyl)-4,5-dimethyl-1,3,2-dioxaborolane Chemical compound C1=C(C)C=C([N+]([O-])=O)C(OC)=C1B1OC(C)C(C)O1 SUGJWGQOVBOKGL-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-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
- WWXGIYUDHVOOOL-UHFFFAOYSA-N 2-[4-(2-methoxy-3-nitrophenyl)phenyl]-4,5-dihydro-1h-imidazole Chemical compound C1=CC=C([N+]([O-])=O)C(OC)=C1C1=CC=C(C=2NCCN=2)C=C1 WWXGIYUDHVOOOL-UHFFFAOYSA-N 0.000 description 1
- RDFXDLZHDPZTFQ-UHFFFAOYSA-N 2-amino-6-[3-(2H-tetrazol-5-yl)phenyl]phenol hydrochloride Chemical compound Cl.NC1=CC=CC(C=2C=C(C=CC=2)C=2NN=NN=2)=C1O RDFXDLZHDPZTFQ-UHFFFAOYSA-N 0.000 description 1
- ZGOPPZVALITMSI-UHFFFAOYSA-N 2-amino-6-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]phenol Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C=2NCCN=2)=C1O ZGOPPZVALITMSI-UHFFFAOYSA-N 0.000 description 1
- MEYRABVEYCFHHB-UHFFFAOYSA-N 2-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Br MEYRABVEYCFHHB-UHFFFAOYSA-N 0.000 description 1
- MTIDYGLTAOZOGU-UHFFFAOYSA-N 2-bromo-4-methylphenol Chemical compound CC1=CC=C(O)C(Br)=C1 MTIDYGLTAOZOGU-UHFFFAOYSA-N 0.000 description 1
- ZHDRDZMTEOIWSX-UHFFFAOYSA-N 2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound CC1=NC(C(O)=O)=CS1 ZHDRDZMTEOIWSX-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- CJXJFSNESZDOGK-UHFFFAOYSA-N 2-o-tert-butyl 4-o-ethyl 3,5-dimethyl-1h-pyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C(=O)OC(C)(C)C)=C1C CJXJFSNESZDOGK-UHFFFAOYSA-N 0.000 description 1
- HZYVZWDZRVOADV-UHFFFAOYSA-N 3-(2-methoxy-5-methyl-3-nitrophenyl)benzoic acid Chemical compound C1=C(C)C=C([N+]([O-])=O)C(OC)=C1C1=CC=CC(C(O)=O)=C1 HZYVZWDZRVOADV-UHFFFAOYSA-N 0.000 description 1
- ZXLYSSHNDUXXIN-UHFFFAOYSA-N 3-(3-amino-2-hydroxyphenyl)benzoic acid Chemical compound NC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1O ZXLYSSHNDUXXIN-UHFFFAOYSA-N 0.000 description 1
- BYKMJZOYMLUGMW-UHFFFAOYSA-N 3-(3-amino-5-fluoro-2-hydroxyphenyl)benzoic acid;hydrochloride Chemical compound Cl.NC1=CC(F)=CC(C=2C=C(C=CC=2)C(O)=O)=C1O BYKMJZOYMLUGMW-UHFFFAOYSA-N 0.000 description 1
- BJVLFJADOVATRU-UHFFFAOYSA-N 3-(3-methylphenyl)benzoic acid Chemical compound CC1=CC=CC(C=2C=C(C=CC=2)C(O)=O)=C1 BJVLFJADOVATRU-UHFFFAOYSA-N 0.000 description 1
- NCSTWHYWOVZDOC-UHFFFAOYSA-N 3-(4-bromophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(Br)C=C1 NCSTWHYWOVZDOC-UHFFFAOYSA-N 0.000 description 1
- STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 1
- VQQLWBUTTMNMFT-UHFFFAOYSA-N 3-bromothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC=CC=1Br VQQLWBUTTMNMFT-UHFFFAOYSA-N 0.000 description 1
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 1
- NHLAPJMCARJFOG-UHFFFAOYSA-N 3-methyl-1,4-dihydropyrazol-5-one Chemical compound CC1=NNC(=O)C1 NHLAPJMCARJFOG-UHFFFAOYSA-N 0.000 description 1
- BHUVICYZDBUMIU-UHFFFAOYSA-N 4,5-dibromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=C(Br)O1 BHUVICYZDBUMIU-UHFFFAOYSA-N 0.000 description 1
- YFGCXBAESOBLEH-UHFFFAOYSA-N 4-(3-amino-2-hydroxyphenyl)furan-2-carboxylic acid Chemical compound NC1=CC=CC(C=2C=C(OC=2)C(O)=O)=C1O YFGCXBAESOBLEH-UHFFFAOYSA-N 0.000 description 1
- SPKLAKKKRAUAPC-UHFFFAOYSA-N 4-(3-amino-2-methoxyphenyl)thiophene-2-carboxylic acid;hydrobromide Chemical compound Br.COC1=C(N)C=CC=C1C1=CSC(C(O)=O)=C1 SPKLAKKKRAUAPC-UHFFFAOYSA-N 0.000 description 1
- MOXOFSFWYLTCFU-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalen-2-amine Chemical compound C1CCCC2=CC(N)=CC=C21 MOXOFSFWYLTCFU-UHFFFAOYSA-N 0.000 description 1
- MWEHFNSBOUGDRG-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)furan-2-carboxylic acid Chemical compound NC1=CC=CC(C=2OC(=CC=2)C(O)=O)=C1O MWEHFNSBOUGDRG-UHFFFAOYSA-N 0.000 description 1
- LWLQCLOEHJOGEL-UHFFFAOYSA-N 5-(3-amino-2-hydroxyphenyl)thiophene-2-carboxylic acid Chemical compound NC1=CC=CC(C=2SC(=CC=2)C(O)=O)=C1O LWLQCLOEHJOGEL-UHFFFAOYSA-N 0.000 description 1
- XTSAEIQNMRIQAS-UHFFFAOYSA-N 5-bromo-3,3-dimethyl-1,2-dihydroindene Chemical compound C1=C(Br)C=C2C(C)(C)CCC2=C1 XTSAEIQNMRIQAS-UHFFFAOYSA-N 0.000 description 1
- YVTQHZDUDUCGRD-UHFFFAOYSA-N 5-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)O1 YVTQHZDUDUCGRD-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- PWJXTSSQVFCSQT-UHFFFAOYSA-N B1CCOC1 Chemical compound B1CCOC1 PWJXTSSQVFCSQT-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- SCGDITKQRLKVKV-UHFFFAOYSA-N C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=CC(C(O)=O)=C1 SCGDITKQRLKVKV-UHFFFAOYSA-N 0.000 description 1
- RHHYSPBQTAWZMA-UHFFFAOYSA-N C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)S1 Chemical compound C1=C2C(C)CCC2=CC=C1N(C1=O)N=C(C)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)S1 RHHYSPBQTAWZMA-UHFFFAOYSA-N 0.000 description 1
- AALUTIQNMWNKDY-UHFFFAOYSA-N CC1(CC2=C(C1)C=C(C=C2)OC(=O)NNC(=O)O)C Chemical compound CC1(CC2=C(C1)C=C(C=C2)OC(=O)NNC(=O)O)C AALUTIQNMWNKDY-UHFFFAOYSA-N 0.000 description 1
- HKQAXHAOJCYZOG-UHFFFAOYSA-N CC1=NN(C(=C=O)C1=NNc1cccc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCCc2c1 Chemical compound CC1=NN(C(=C=O)C1=NNc1cccc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCCc2c1 HKQAXHAOJCYZOG-UHFFFAOYSA-N 0.000 description 1
- MMTLVDNORLIAIU-UHFFFAOYSA-N CC1=NN(C(=O)C1=NNc1cc(F)cc(-c2ccc(cc2)C(O)=O)c1O)c1ccc2CCCCc2c1 Chemical compound CC1=NN(C(=O)C1=NNc1cc(F)cc(-c2ccc(cc2)C(O)=O)c1O)c1ccc2CCCCc2c1 MMTLVDNORLIAIU-UHFFFAOYSA-N 0.000 description 1
- FHRVZSDJHKEDKH-UHFFFAOYSA-N CC1=NN(C(=O)C1=NNc1cc(F)cc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCc2c1 Chemical compound CC1=NN(C(=O)C1=NNc1cc(F)cc(-c2cccc(c2)C(O)=O)c1O)c1ccc2CCc2c1 FHRVZSDJHKEDKH-UHFFFAOYSA-N 0.000 description 1
- NWYLDIVQUVULLO-UHFFFAOYSA-N CC1=NN(C(=O)C1=NNc1cccc(-c2ccc(o2)C(O)=O)c1O)c1ccc2CCc2c1 Chemical compound CC1=NN(C(=O)C1=NNc1cccc(-c2ccc(o2)C(O)=O)c1O)c1ccc2CCc2c1 NWYLDIVQUVULLO-UHFFFAOYSA-N 0.000 description 1
- WITKGWRONMFQRY-UHFFFAOYSA-N CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 Chemical compound CC1=NN(C=2C=C3C(C)(C)CCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 WITKGWRONMFQRY-UHFFFAOYSA-N 0.000 description 1
- KRZYNXDIKJPGSW-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)O1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)O1 KRZYNXDIKJPGSW-UHFFFAOYSA-N 0.000 description 1
- PBZCMZTWSGMRAT-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)S1 PBZCMZTWSGMRAT-UHFFFAOYSA-N 0.000 description 1
- QBDXUXWAXZWBCX-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(F)=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(F)=CC=1C1=CC=CC(C(O)=O)=C1 QBDXUXWAXZWBCX-UHFFFAOYSA-N 0.000 description 1
- YORDVZDGTJBDHG-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C(C=1)=CC=CC=1C1=NN=NN1 YORDVZDGTJBDHG-UHFFFAOYSA-N 0.000 description 1
- SPQCOZAUCWMPPM-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)S1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)S1 SPQCOZAUCWMPPM-UHFFFAOYSA-N 0.000 description 1
- MAQPZOYJBLWUHM-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=CC(C(O)=O)=C1 MAQPZOYJBLWUHM-UHFFFAOYSA-N 0.000 description 1
- OSWYSYNINHASLL-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)O1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC(C)=CC=1C1=CC=C(C(O)=O)O1 OSWYSYNINHASLL-UHFFFAOYSA-N 0.000 description 1
- FIJXLXNJSOYTGV-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC(C(O)=O)=C(C)O1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC(C(O)=O)=C(C)O1 FIJXLXNJSOYTGV-UHFFFAOYSA-N 0.000 description 1
- BDGGFTDRPHKXFC-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=CC=C(C(O)=O)O1 BDGGFTDRPHKXFC-UHFFFAOYSA-N 0.000 description 1
- VQDQTUFMOOJRFL-UHFFFAOYSA-N CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=COC(C(O)=O)=C1 Chemical compound CC1=NN(C=2C=C3CCCCC3=CC=2)C(=O)C1=NNC(C=1O)=CC=CC=1C1=COC(C(O)=O)=C1 VQDQTUFMOOJRFL-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 210000002361 Megakaryocyte Progenitor Cell Anatomy 0.000 description 1
- 101001033276 Mus musculus Interleukin-3 Proteins 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 108700022598 Ovis aries megapoietin Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000020584 Polyploidy Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229940127323 Thrombopoietin Receptor Agonists Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- TYVSEIJPYOVOSB-UHFFFAOYSA-N [(1,1,3,3-tetramethyl-2H-inden-5-yl)oxycarbonylamino]carbamic acid Chemical compound CC1(CC(C2=C1C=CC(=C2)OC(=O)NNC(=O)O)(C)C)C TYVSEIJPYOVOSB-UHFFFAOYSA-N 0.000 description 1
- HZDGZNMTOCJOOV-UHFFFAOYSA-N [(3,3-dimethyl-1,2-dihydroinden-5-yl)oxycarbonylamino]carbamic acid Chemical compound CC1(CCC2=C1C=C(C=C2)OC(=O)NNC(=O)O)C HZDGZNMTOCJOOV-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- PWQLZSHJRGGLBC-UHFFFAOYSA-N acetonitrile;carbon dioxide Chemical compound CC#N.O=C=O PWQLZSHJRGGLBC-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- UMIVXZPTRXBADB-UHFFFAOYSA-N benzocyclobutene Chemical compound C1=CC=C2CCC2=C1 UMIVXZPTRXBADB-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229910000423 chromium oxide Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000000430 cytokine receptor antagonist Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000034311 endomitotic cell cycle Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- SEVBMIOVNCPFNQ-UHFFFAOYSA-N ethyl 5-(2-methoxy-3-nitrophenyl)-1,2,4-trimethylpyrrole-3-carboxylate Chemical compound CN1C(C)=C(C(=O)OCC)C(C)=C1C1=CC=CC([N+]([O-])=O)=C1OC SEVBMIOVNCPFNQ-UHFFFAOYSA-N 0.000 description 1
- FRRCAVMHRGDBRZ-UHFFFAOYSA-N ethyl acetate;3-oxobutanoic acid Chemical compound CCOC(C)=O.CC(=O)CC(O)=O FRRCAVMHRGDBRZ-UHFFFAOYSA-N 0.000 description 1
- JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229940083761 high-ceiling diuretics pyrazolone derivative Drugs 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- FZRNJOXQNWVMIH-UHFFFAOYSA-N lithium;hydrate Chemical compound [Li].O FZRNJOXQNWVMIH-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- IHEBQVQNNICYOZ-UHFFFAOYSA-N methyl 5-(2-methoxy-3-nitrophenyl)-2-methylfuran-3-carboxylate Chemical compound O1C(C)=C(C(=O)OC)C=C1C1=CC=CC([N+]([O-])=O)=C1OC IHEBQVQNNICYOZ-UHFFFAOYSA-N 0.000 description 1
- GODOLEOCBPESIQ-UHFFFAOYSA-N methyl 5-(2-methoxy-3-nitrophenyl)furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1C1=CC=CC([N+]([O-])=O)=C1OC GODOLEOCBPESIQ-UHFFFAOYSA-N 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- SBHSXURZUDRJBS-UHFFFAOYSA-N tert-butyl n-(3,3-dimethylinden-5-yl)-n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(C(=O)OC(C)(C)C)C1=CC=C2C=CC(C)(C)C2=C1 SBHSXURZUDRJBS-UHFFFAOYSA-N 0.000 description 1
- QYZUVRASNWIITO-UHFFFAOYSA-N tert-butyl n-(3-ethyl-2,3-dihydro-1h-inden-5-yl)-n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound C1=C(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C2C(CC)CCC2=C1 QYZUVRASNWIITO-UHFFFAOYSA-N 0.000 description 1
- NNBGENCRTWJCDM-UHFFFAOYSA-N tert-butyl n-(3-methyl-1h-inden-5-yl)-n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound C1=C(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C2C(C)=CCC2=C1 NNBGENCRTWJCDM-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003584 thiosemicarbazones Chemical class 0.000 description 1
- 230000003582 thrombocytopenic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810000346 | 2008-01-10 | ||
| CNA2008100003466A CN101481352A (zh) | 2008-01-10 | 2008-01-10 | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 |
| PCT/CN2009/000001 WO2009092276A1 (zh) | 2008-01-10 | 2009-01-04 | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2533366T3 true ES2533366T3 (es) | 2015-04-09 |
Family
ID=40878665
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09703490.4T Active ES2533366T3 (es) | 2008-01-10 | 2009-01-04 | Derivados azoicos de pirazolona biciclo-sustituidos, procedimiento de preparacion y utilización farmacéutica de los mismos |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8367710B2 (https=) |
| EP (1) | EP2236500B1 (https=) |
| JP (1) | JP5441269B2 (https=) |
| KR (1) | KR101556808B1 (https=) |
| CN (2) | CN101481352A (https=) |
| AU (1) | AU2009207966B2 (https=) |
| BR (1) | BRPI0907234B1 (https=) |
| CA (1) | CA2711535C (https=) |
| ES (1) | ES2533366T3 (https=) |
| MX (1) | MX2010007553A (https=) |
| PT (1) | PT2236500E (https=) |
| RU (1) | RU2488582C2 (https=) |
| UA (1) | UA101172C2 (https=) |
| WO (1) | WO2009092276A1 (https=) |
| ZA (1) | ZA201004794B (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0302486D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
| CN101921232A (zh) * | 2009-06-11 | 2010-12-22 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物的盐,其制备方法及其在医药上的应用 |
| JP5704073B2 (ja) * | 2009-10-23 | 2015-04-22 | 日産化学工業株式会社 | 縮環へテロ環化合物及びトロンボポエチンレセプター活性化剤 |
| CN103360317B (zh) * | 2012-04-11 | 2016-12-14 | 齐鲁制药有限公司 | 双环取代吡唑酮偶氮类衍生物、其制备方法及用途 |
| CN103724206A (zh) * | 2014-01-17 | 2014-04-16 | 青岛农业大学 | 化合物2-溴-4-氟-6-硝基苯酚的制备方法和农用生物活性 |
| WO2015111085A2 (en) * | 2014-01-27 | 2015-07-30 | Cadila Healthcare Limited | Processes for the preparation of eltrombopag and pharmaceutically acceptable salts, solvates and intermediates thereof |
| US9849077B2 (en) | 2014-03-10 | 2017-12-26 | Mary Kay Inc. | Skin lightening compositions |
| CN104592033A (zh) * | 2014-12-30 | 2015-05-06 | 杭州和泽医药科技有限公司 | 一种艾曲波帕关键中间体的合成方法 |
| CN106994120B (zh) * | 2016-01-22 | 2021-05-14 | 江苏恒瑞医药股份有限公司 | 一种含有双环取代吡唑酮偶氮类衍生物或其盐的药物组合物及其制备方法 |
| TW201726129A (zh) * | 2016-01-22 | 2017-08-01 | 江蘇恆瑞醫藥股份有限公司 | 一種含有雙環取代吡唑酮偶氮類衍生物或其鹽的藥物組成物及其製備方法 |
| TWI762556B (zh) * | 2017-01-19 | 2022-05-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種雙環取代吡唑酮偶氮類衍生物的製備方法及其中間體 |
| CN110028497B (zh) * | 2018-01-11 | 2020-11-17 | 江苏恒瑞医药股份有限公司 | 一种血小板生成素模拟物的乙醇胺盐的结晶形式及制备方法 |
| CN113226463A (zh) * | 2019-01-08 | 2021-08-06 | 江苏恒瑞医药股份有限公司 | 双环取代吡唑酮偶氮类衍生物的给药方案 |
| CN112062699B (zh) * | 2020-11-13 | 2021-02-26 | 苏州开元民生科技股份有限公司 | 一种邻氨基苯硫酚的制备方法 |
| WO2022228551A1 (zh) * | 2021-04-30 | 2022-11-03 | 江苏恒瑞医药股份有限公司 | 一种血小板生成素受体激动剂的给药方案 |
| US20250144077A1 (en) * | 2022-01-25 | 2025-05-08 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Dosage regimen for thrombopoietin receptor agonist |
| WO2025140275A1 (zh) * | 2023-12-25 | 2025-07-03 | 江苏恒瑞医药股份有限公司 | 取代吡唑啉偶氮衍生物的磷酸酯化合物或其可药用盐 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB775216A (en) * | 1954-02-23 | 1957-05-22 | Sandoz Ltd | Improvements in or relating to monoazo dyestuffs of the benzene-azo-pyrazolone series and their chromium-complex compounds |
| GB806709A (en) * | 1955-04-22 | 1958-12-31 | Bayer Ag | Monoazo dyestuffs of the benzene-azo-pyrazolone series and metal complexes thereof |
| TR199701526T1 (xx) | 1995-06-07 | 1998-03-21 | Glaxo Group Limited | Bir trombopoietin resept�r�ne ba�lanan peptitler ve bile�ikler. |
| US5869451A (en) | 1995-06-07 | 1999-02-09 | Glaxo Group Limited | Peptides and compounds that bind to a receptor |
| JPH111477A (ja) | 1997-06-12 | 1999-01-06 | Hokuriku Seiyaku Co Ltd | １，４−ベンゾジアゼピン誘導体及びその用途 |
| AU9265698A (en) | 1997-09-02 | 1999-03-22 | Boehringer Mannheim Gmbh | Mpl-receptor ligands, process for their preparation, medicaments containing themand their use for the treatment and prevention of thrombocytopaenia and anaemia |
| JP2002529502A (ja) | 1998-11-17 | 2002-09-10 | スミスクライン・ビーチャム・コーポレイション | 血小板減少症の治療法 |
| WO2000039773A1 (de) | 1998-12-14 | 2000-07-06 | Mannesmann Ag | Verfahren zur übertragung von verkehrsinformationen |
| GC0000177A (en) | 1998-12-17 | 2006-03-29 | Smithkline Beecham | Thrombopoietin mimetics |
| KR20020069183A (ko) | 1999-07-26 | 2002-08-29 | 시오노기세이야쿠가부시키가이샤 | 트롬보포이에틴 작동성을 나타내는 의약 조성물 |
| EP1213965B1 (en) | 1999-09-10 | 2006-01-18 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
| WO2001034585A1 (en) | 1999-11-05 | 2001-05-17 | Smithkline Beecham Corporation | Semicarbazone derivatives and their use as thrombopoietin mimetics |
| AU2079901A (en) | 1999-12-06 | 2001-06-12 | Smithkline Beecham Corporation | Thrombopoietin mimetics |
| TWI284639B (en) | 2000-01-24 | 2007-08-01 | Shionogi & Co | A compound having thrombopoietin receptor agonistic effect |
| CY2010012I2 (el) * | 2000-05-25 | 2020-05-29 | Novartis Ag | Μιμητικα θρομβοποιητινης |
| TWI280128B (en) * | 2002-05-22 | 2007-05-01 | Smithkline Beecham Corp | 3'-[(2Z)-[1-(3,4- dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine) |
| EP2387998A1 (en) * | 2003-04-29 | 2011-11-23 | Glaxosmithkline LLC | Methods for treating degenerative diseases/injuries |
| DE602004019685D1 (de) | 2003-12-26 | 2009-04-09 | Allergan Inc | DISUBSTITUIERTE CHALCOGENOXIME MIT ANTAGONISTISCHER WIRKUNG AM RAR(Gamma)-RETINOIDREZEPTOR |
| JP4518819B2 (ja) * | 2004-03-17 | 2010-08-04 | 富士フイルム株式会社 | アゾ化合物 |
| AU2005314788B2 (en) * | 2004-12-14 | 2011-09-22 | Nissan Chemical Industries, Ltd. | Amide compound and thrombopoietin receptor activator |
| JP2009511603A (ja) * | 2005-10-13 | 2009-03-19 | スミスクライン・ビーチャム・コーポレイション | 貯蔵中の血小板の有効性を維持する方法 |
| CA2630234A1 (en) * | 2005-11-23 | 2007-05-31 | Ligand Pharmaceuticals Inc. | Thrombopoietin activity modulating compounds and methods |
-
2008
- 2008-01-10 CN CNA2008100003466A patent/CN101481352A/zh active Pending
-
2009
- 2009-01-04 ES ES09703490.4T patent/ES2533366T3/es active Active
- 2009-01-04 PT PT97034904T patent/PT2236500E/pt unknown
- 2009-01-04 WO PCT/CN2009/000001 patent/WO2009092276A1/zh not_active Ceased
- 2009-01-04 US US12/812,119 patent/US8367710B2/en active Active
- 2009-01-04 AU AU2009207966A patent/AU2009207966B2/en active Active
- 2009-01-04 CA CA2711535A patent/CA2711535C/en active Active
- 2009-01-04 CN CN2009800001980A patent/CN101679286B/zh active Active
- 2009-01-04 EP EP09703490.4A patent/EP2236500B1/en active Active
- 2009-01-04 MX MX2010007553A patent/MX2010007553A/es active IP Right Grant
- 2009-01-04 UA UAA201008616A patent/UA101172C2/ru unknown
- 2009-01-04 BR BRPI0907234-9A patent/BRPI0907234B1/pt active IP Right Grant
- 2009-01-04 KR KR1020107017630A patent/KR101556808B1/ko active Active
- 2009-01-04 JP JP2010541680A patent/JP5441269B2/ja active Active
- 2009-01-04 RU RU2010127786/04A patent/RU2488582C2/ru active
-
2010
- 2010-07-07 ZA ZA2010/04794A patent/ZA201004794B/en unknown
-
2013
- 2013-01-16 US US13/742,633 patent/US20130123507A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP5441269B2 (ja) | 2014-03-12 |
| BRPI0907234B1 (pt) | 2021-08-10 |
| JP2011509263A (ja) | 2011-03-24 |
| PT2236500E (pt) | 2015-04-07 |
| RU2010127786A (ru) | 2012-02-20 |
| KR101556808B1 (ko) | 2015-10-01 |
| CA2711535C (en) | 2015-12-15 |
| BRPI0907234A2 (pt) | 2020-08-04 |
| KR20100120141A (ko) | 2010-11-12 |
| CN101679286A (zh) | 2010-03-24 |
| US20100316601A1 (en) | 2010-12-16 |
| RU2488582C2 (ru) | 2013-07-27 |
| WO2009092276A1 (zh) | 2009-07-30 |
| EP2236500B1 (en) | 2014-12-24 |
| HK1134818A1 (en) | 2010-05-14 |
| AU2009207966A1 (en) | 2009-07-30 |
| MX2010007553A (es) | 2010-10-04 |
| EP2236500A1 (en) | 2010-10-06 |
| CA2711535A1 (en) | 2009-07-30 |
| CN101481352A (zh) | 2009-07-15 |
| EP2236500A4 (en) | 2012-08-22 |
| CN101679286B (zh) | 2011-06-08 |
| UA101172C2 (ru) | 2013-03-11 |
| US20130123507A1 (en) | 2013-05-16 |
| AU2009207966B2 (en) | 2013-03-21 |
| US8367710B2 (en) | 2013-02-05 |
| ZA201004794B (en) | 2011-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2533366T3 (es) | Derivados azoicos de pirazolona biciclo-sustituidos, procedimiento de preparacion y utilización farmacéutica de los mismos | |
| JP2011509263A5 (https=) | ||
| CA2762916C (en) | Salts of bicyclo-substituted pyrazolon azo derivatives, preparation method and use thereof | |
| JP3813875B2 (ja) | トロンボポエチン摸倣物 | |
| US6552008B1 (en) | Thrombopoietin mimetics | |
| ES2275567T3 (es) | Mimeticos de4 trombopoietina. | |
| ES2212138T3 (es) | Derivados de la distamicina benzo-heterociclica, su procedimiento de preparacion y su uso como agentes antitumorales o antivirales. | |
| JPH0623193B2 (ja) | 新規なジスタマイシンａ同族体、その製造方法およびそれを含有する医薬組成物 | |
| CN103360317B (zh) | 双环取代吡唑酮偶氮类衍生物、其制备方法及用途 | |
| US6858630B2 (en) | Naphthimidazole derivatives and their use as thrombopoietin mimetics | |
| CN101928281A (zh) | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 | |
| WO2025077774A1 (zh) | 一种at2r拮抗剂及其用途 | |
| JP2004527541A (ja) | トロンボポエチン模倣物 | |
| TWI437985B (zh) | 雙環取代吡唑酮偶氮類衍生物、其製備方法及其在醫藥上的應用 | |
| HK1134818B (en) | Bicyclo-substituted pyrazolon azo derivatives, preparation process and pharmaceutical use thereof |