USRE48140E1 - Furanone derivative - Google Patents
Furanone derivative Download PDFInfo
- Publication number
- USRE48140E1 USRE48140E1 US15/967,323 US201215967323A USRE48140E US RE48140 E1 USRE48140 E1 US RE48140E1 US 201215967323 A US201215967323 A US 201215967323A US RE48140 E USRE48140 E US RE48140E
- Authority
- US
- United States
- Prior art keywords
- mmol
- dihydrofuran
- oxo
- carboxylate
- ethyl
- 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
- 150000002241 furanones Chemical class 0.000 title claims abstract description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 37
- 125000003277 amino group Chemical group 0.000 claims abstract description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
- 125000005843 halogen group Chemical group 0.000 claims abstract description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 6
- 150000003839 salts Chemical class 0.000 claims description 40
- 239000000126 substance Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 abstract description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 780
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 616
- 150000001875 compounds Chemical class 0.000 description 386
- 238000005160 1H NMR spectroscopy Methods 0.000 description 292
- 239000007787 solid Substances 0.000 description 286
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 283
- 239000000243 solution Substances 0.000 description 249
- 238000000034 method Methods 0.000 description 200
- 239000000203 mixture Substances 0.000 description 182
- 238000001914 filtration Methods 0.000 description 140
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 138
- 239000002244 precipitate Substances 0.000 description 133
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- 239000011541 reaction mixture Substances 0.000 description 111
- KAIWRKYDYWYFIT-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=N1 KAIWRKYDYWYFIT-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 86
- 238000002953 preparative HPLC Methods 0.000 description 75
- 239000002904 solvent Substances 0.000 description 75
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 61
- 239000011701 zinc Substances 0.000 description 56
- -1 dihydroisoquinolyl Chemical group 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 38
- 229960002429 proline Drugs 0.000 description 38
- 229930182821 L-proline Natural products 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 239000003054 catalyst Substances 0.000 description 31
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 30
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 29
- 229910052725 zinc Inorganic materials 0.000 description 29
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 28
- 239000000706 filtrate Substances 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- PGMYNVMHWVMOPP-UHFFFAOYSA-N ethyl 2-ethoxy-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(OCC)OCC1=O PGMYNVMHWVMOPP-UHFFFAOYSA-N 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 0 *C1=C(N([2*])[3*])O/C(=C\C2=CNC3=NC=CC=C23)C1=O.[4*]C Chemical compound *C1=C(N([2*])[3*])O/C(=C\C2=CNC3=NC=CC=C23)C1=O.[4*]C 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 102100030960 DNA replication licensing factor MCM2 Human genes 0.000 description 11
- 101000583807 Homo sapiens DNA replication licensing factor MCM2 Proteins 0.000 description 11
- 101001018431 Homo sapiens DNA replication licensing factor MCM7 Proteins 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 11
- 230000002378 acidificating effect Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 230000026731 phosphorylation Effects 0.000 description 10
- 238000006366 phosphorylation reaction Methods 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 239000013058 crude material Substances 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
- 239000005695 Ammonium acetate Substances 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 235000019257 ammonium acetate Nutrition 0.000 description 7
- 229940043376 ammonium acetate Drugs 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- QRVSDVDFJFKYKA-UHFFFAOYSA-N dipropan-2-yl propanedioate Chemical compound CC(C)OC(=O)CC(=O)OC(C)C QRVSDVDFJFKYKA-UHFFFAOYSA-N 0.000 description 6
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- HFLMYYLFSNEOOT-UHFFFAOYSA-N methyl 4-chloro-3-oxobutanoate Chemical compound COC(=O)CC(=O)CCl HFLMYYLFSNEOOT-UHFFFAOYSA-N 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 239000012131 assay buffer Substances 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- BNNCZCRRYDVISK-UHFFFAOYSA-N propan-2-yl 4-oxo-2-propan-2-yloxyfuran-3-carboxylate Chemical compound CC(C)OC(=O)C1=C(OC(C)C)OCC1=O BNNCZCRRYDVISK-UHFFFAOYSA-N 0.000 description 5
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 4
- PIIZYNQECPTVEO-UHFFFAOYSA-N 4-nitro-m-cresol Chemical compound CC1=CC(O)=CC=C1[N+]([O-])=O PIIZYNQECPTVEO-UHFFFAOYSA-N 0.000 description 4
- RFLDTPXOHMJIHW-UHFFFAOYSA-N 4-oxofuran-3-carboxylic acid Chemical compound OC(=O)C1=COCC1=O RFLDTPXOHMJIHW-UHFFFAOYSA-N 0.000 description 4
- 241000283074 Equus asinus Species 0.000 description 4
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000006848 alicyclic heterocyclic group Chemical group 0.000 description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 description 3
- AZOKNCQXTZPXBI-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(OCCOC)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(OCCOC)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AZOKNCQXTZPXBI-MOSHPQCFSA-N 0.000 description 3
- 230000004543 DNA replication Effects 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000945740 Homo sapiens Cell division cycle 7-related protein kinase Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 3
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- YUVNUXDEMUKFFG-UHFFFAOYSA-N ethyl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCN(C)C)C=C1C YUVNUXDEMUKFFG-UHFFFAOYSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- FFQFWGSRLHOBAN-UHFFFAOYSA-N methyl 2-(4-fluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NC1=CC=C(F)C=C1 FFQFWGSRLHOBAN-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 238000005809 transesterification reaction Methods 0.000 description 3
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 2
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- ZSFOKJYVTQSSKV-UHFFFAOYSA-N 1-methyl-4-[2-(3-methyl-4-nitrophenoxy)ethyl]piperazine Chemical compound C1CN(C)CCN1CCOC1=CC=C([N+]([O-])=O)C(C)=C1 ZSFOKJYVTQSSKV-UHFFFAOYSA-N 0.000 description 2
- YWPHBESVUYOQNT-UHFFFAOYSA-N 1-o-ethyl 3-o-(2-methoxyethyl) propanedioate Chemical compound CCOC(=O)CC(=O)OCCOC YWPHBESVUYOQNT-UHFFFAOYSA-N 0.000 description 2
- BJBWVEANJVANKR-UHFFFAOYSA-N 1-o-ethyl 3-o-[2-[(2-methylpropan-2-yl)oxycarbonyloxy]ethyl] propanedioate Chemical compound CCOC(=O)CC(=O)OCCOC(=O)OC(C)(C)C BJBWVEANJVANKR-UHFFFAOYSA-N 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- TYXUQTDNNWVPDW-UHFFFAOYSA-N 2-(2,3-dihydroindol-1-yl)-4-oxofuran-3-carboxylic acid Chemical compound O1CC(=O)C(C(=O)O)=C1N1C2=CC=CC=C2CC1 TYXUQTDNNWVPDW-UHFFFAOYSA-N 0.000 description 2
- GPIYPNRMOGQYQI-UHFFFAOYSA-N 2-(3-methyl-4-nitrophenoxy)ethanol Chemical compound CC1=CC(OCCO)=CC=C1[N+]([O-])=O GPIYPNRMOGQYQI-UHFFFAOYSA-N 0.000 description 2
- NWASPLRNFPQETR-UHFFFAOYSA-N 2-(4-amino-3-methylphenoxy)ethanol Chemical compound CC1=CC(OCCO)=CC=C1N NWASPLRNFPQETR-UHFFFAOYSA-N 0.000 description 2
- YQBACZGTCZERHM-UHFFFAOYSA-N 2-(4-amino-n,3-dimethylanilino)ethanol Chemical compound OCCN(C)C1=CC=C(N)C(C)=C1 YQBACZGTCZERHM-UHFFFAOYSA-N 0.000 description 2
- BAMHYYNEQXZACS-UHFFFAOYSA-N 2-(n,3-dimethyl-4-nitroanilino)ethanol Chemical compound OCCN(C)C1=CC=C([N+]([O-])=O)C(C)=C1 BAMHYYNEQXZACS-UHFFFAOYSA-N 0.000 description 2
- KSVZJMATKCYSCX-UHFFFAOYSA-N 2-[(3-methyl-4-nitrophenoxy)methyl]pyrimidine Chemical compound C1=C([N+]([O-])=O)C(C)=CC(OCC=2N=CC=CN=2)=C1 KSVZJMATKCYSCX-UHFFFAOYSA-N 0.000 description 2
- AWOAQLTUMGMCKO-UHFFFAOYSA-N 2-[2-(3-methyl-4-nitrophenoxy)ethyl]pyridine Chemical compound C1=C([N+]([O-])=O)C(C)=CC(OCCC=2N=CC=CC=2)=C1 AWOAQLTUMGMCKO-UHFFFAOYSA-N 0.000 description 2
- CSZXKLIJRUAGMT-UHFFFAOYSA-N 2-[4-[2-hydroxyethyl(methyl)amino]-2-methylanilino]-4-oxofuran-3-carboxylic acid Chemical compound CC1=CC(N(CCO)C)=CC=C1NC1=C(C(O)=O)C(=O)CO1 CSZXKLIJRUAGMT-UHFFFAOYSA-N 0.000 description 2
- IPOVOSHRRIJKBR-UHFFFAOYSA-N 2-ethylpropanedioyl dichloride Chemical compound CCC(C(Cl)=O)C(Cl)=O IPOVOSHRRIJKBR-UHFFFAOYSA-N 0.000 description 2
- SYWGASPWCLCLRI-UHFFFAOYSA-N 2-methoxyethyl 2-(1h-azepin-2-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCCOC)=C1C1=CC=CC=CN1 SYWGASPWCLCLRI-UHFFFAOYSA-N 0.000 description 2
- XGKZQAUEOQPHAQ-UHFFFAOYSA-N 2-methoxyethyl 2-(4-fluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCCOC)=C1NC1=CC=C(F)C=C1 XGKZQAUEOQPHAQ-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- QCSSKIQBLKPBCX-UHFFFAOYSA-N 2-methyl-4-(2-pyridin-2-ylethoxy)aniline Chemical compound C1=C(N)C(C)=CC(OCCC=2N=CC=CC=2)=C1 QCSSKIQBLKPBCX-UHFFFAOYSA-N 0.000 description 2
- AVMLQGQQJMMLDD-UHFFFAOYSA-N 2-methyl-4-(pyrimidin-2-ylmethoxy)aniline Chemical compound C1=C(N)C(C)=CC(OCC=2N=CC=CN=2)=C1 AVMLQGQQJMMLDD-UHFFFAOYSA-N 0.000 description 2
- XYZQBLHMLRXOET-UHFFFAOYSA-N 2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]aniline Chemical compound C1CN(C)CCN1CCOC1=CC=C(N)C(C)=C1 XYZQBLHMLRXOET-UHFFFAOYSA-N 0.000 description 2
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 2
- AIQPCXFIPDZVQJ-UHFFFAOYSA-N 3-oxa-2-azoniabicyclo[2.2.2]oct-5-ene;chloride Chemical compound Cl.O1NC2CCC1C=C2 AIQPCXFIPDZVQJ-UHFFFAOYSA-N 0.000 description 2
- VDEYPLWBCCBZAB-UHFFFAOYSA-N 4-(2,2,2-trifluoroethyl)piperazin-1-amine Chemical compound NN1CCN(CC(F)(F)F)CC1 VDEYPLWBCCBZAB-UHFFFAOYSA-N 0.000 description 2
- MIBZTIHBNXSNLQ-UHFFFAOYSA-N 4-(2-chloroethoxy)-2-methyl-1-nitrobenzene Chemical compound CC1=CC(OCCCl)=CC=C1[N+]([O-])=O MIBZTIHBNXSNLQ-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- OQUKPEYUVQSUIM-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-2-methylaniline Chemical compound CN(C)CC1=CC=C(N)C(C)=C1 OQUKPEYUVQSUIM-UHFFFAOYSA-N 0.000 description 2
- RKTQEVMZBCBOSB-UHFFFAOYSA-N 4-aminocyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1CCC(O)CC1 RKTQEVMZBCBOSB-UHFFFAOYSA-N 0.000 description 2
- ZRMBMVOGUOPEAZ-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,7-naphthyridine;dihydrochloride Chemical compound Cl.Cl.C1=CN=C2CNCCC2=C1 ZRMBMVOGUOPEAZ-UHFFFAOYSA-N 0.000 description 2
- UKNSDRUWZAASLO-UHFFFAOYSA-N 5-(4-propan-2-ylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(C(C)C)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 UKNSDRUWZAASLO-UHFFFAOYSA-N 0.000 description 2
- MFZQJIKENSPRSJ-UHFFFAOYSA-N 5-chloro-1h-pyrrolo[2,3-b]pyridine Chemical compound ClC1=CN=C2NC=CC2=C1 MFZQJIKENSPRSJ-UHFFFAOYSA-N 0.000 description 2
- NKTDCYOZPANZSE-UHFFFAOYSA-N 5-chloro-1h-pyrrolo[2,3-b]pyridine-3-carbaldehyde Chemical compound ClC1=CN=C2NC=C(C=O)C2=C1 NKTDCYOZPANZSE-UHFFFAOYSA-N 0.000 description 2
- ZZSDHUMNIBZFFM-UHFFFAOYSA-N 5-chloro-3-(2-trimethylsilylethynyl)pyridin-2-amine Chemical compound C[Si](C)(C)C#CC1=CC(Cl)=CN=C1N ZZSDHUMNIBZFFM-UHFFFAOYSA-N 0.000 description 2
- DIONPYCYVWCDIG-UHFFFAOYSA-N 5-chloro-3-iodopyridin-2-amine Chemical compound NC1=NC=C(Cl)C=C1I DIONPYCYVWCDIG-UHFFFAOYSA-N 0.000 description 2
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 2
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- NLPOURRUMQZENF-UHFFFAOYSA-N C1CN(C)CCN1CCOC(C=C1C)=CC=C1NC1=C(C(O)=O)C(=O)CO1 Chemical compound C1CN(C)CCN1CCOC(C=C1C)=CC=C1NC1=C(C(O)=O)C(=O)CO1 NLPOURRUMQZENF-UHFFFAOYSA-N 0.000 description 2
- RQYBBEONSJIPGP-PDGQHHTCSA-N CC(=O)O.CN(C)CCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CN(C)CCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RQYBBEONSJIPGP-PDGQHHTCSA-N 0.000 description 2
- GKDFYJDRBNATEA-WQRHYEAKSA-N CC(C)(NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1)C1=CC=CC=C1 Chemical compound CC(C)(NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1)C1=CC=CC=C1 GKDFYJDRBNATEA-WQRHYEAKSA-N 0.000 description 2
- QDZJQSNYTZKIPW-IUXPMGMMSA-N CC(C)OC(=O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QDZJQSNYTZKIPW-IUXPMGMMSA-N 0.000 description 2
- FCEKOSDALBLHGD-GZTJUZNOSA-N CC(C)OC(=O)C1=C(NCC2CCCCC2)C/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NCC2CCCCC2)C/C(=C\C2=CNC3=C2C=CC=N3)C1=O FCEKOSDALBLHGD-GZTJUZNOSA-N 0.000 description 2
- GSMFCPGNCCBTOD-ZDLGFXPLSA-N CC(NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1)C1=CC=CC=C1 Chemical compound CC(NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1)C1=CC=CC=C1 GSMFCPGNCCBTOD-ZDLGFXPLSA-N 0.000 description 2
- SEFUMBSSKYIYBU-CHHVJCJISA-N CC1=C(CNC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)SC=C1 Chemical compound CC1=C(CNC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)SC=C1 SEFUMBSSKYIYBU-CHHVJCJISA-N 0.000 description 2
- BPIJRDNKANOSFF-HMAPJEAMSA-N CC1=C(NC2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(CN(C)C)=C1 Chemical compound CC1=C(NC2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(CN(C)C)=C1 BPIJRDNKANOSFF-HMAPJEAMSA-N 0.000 description 2
- IOVPUSDTYBXUJK-NVMNQCDNSA-N CC1=CC(C)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CC1=CC(C)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 IOVPUSDTYBXUJK-NVMNQCDNSA-N 0.000 description 2
- KYECCRIGONTHGD-NDENLUEZSA-N CC1=CC(OCCO)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(OCCO)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 KYECCRIGONTHGD-NDENLUEZSA-N 0.000 description 2
- RFJXRHBBOAYUPB-PDGQHHTCSA-N CCCCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCCCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RFJXRHBBOAYUPB-PDGQHHTCSA-N 0.000 description 2
- KNWCLRSQALRYTF-ZROIWOOFSA-N CCOC(=O)C1=C(N(C)C(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)C(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O KNWCLRSQALRYTF-ZROIWOOFSA-N 0.000 description 2
- CQURJNSYNNFGDQ-YBEGLDIGSA-N CCOC(=O)C1=C(N2CCC3=C(C2)OC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C2)OC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CQURJNSYNNFGDQ-YBEGLDIGSA-N 0.000 description 2
- XLGMUGOVWHZVGO-YBEGLDIGSA-N CCOC(=O)C1=C(N2CCC3=C(C2)SC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C2)SC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XLGMUGOVWHZVGO-YBEGLDIGSA-N 0.000 description 2
- OUGAGADONJPCAI-NDENLUEZSA-N CCOC(=O)C1=C(N2CCC3=C(C=C(OC)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C=C(OC)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O OUGAGADONJPCAI-NDENLUEZSA-N 0.000 description 2
- LXXOJAGCKNZMQF-NDENLUEZSA-N CCOC(=O)C1=C(N2CCC3=C(C=CC(OC)=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C=CC(OC)=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LXXOJAGCKNZMQF-NDENLUEZSA-N 0.000 description 2
- DBLDLYUVJGDMMD-UNOMPAQXSA-N CCOC(=O)C1=C(N2CCOC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCOC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DBLDLYUVJGDMMD-UNOMPAQXSA-N 0.000 description 2
- BDLOOGGKJOBMIB-GQTRWRLGSA-N CCOC(=O)C1=C(N2C[C@H](C)O[C@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2C[C@H](C)O[C@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BDLOOGGKJOBMIB-GQTRWRLGSA-N 0.000 description 2
- JZHBMODROBRDLG-STZFKDTASA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCOCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCOCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JZHBMODROBRDLG-STZFKDTASA-N 0.000 description 2
- ZNHDDEBGNUYCIH-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O ZNHDDEBGNUYCIH-YBEGLDIGSA-N 0.000 description 2
- RYLYRAQCKNDDDW-PDGQHHTCSA-N CCOC(=O)C1=C(NC2=CC=C(N(C)C)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NC2=CC=C(N(C)C)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl RYLYRAQCKNDDDW-PDGQHHTCSA-N 0.000 description 2
- UAQBBDNWAFULDP-PXNMLYILSA-N CCOC(=O)C1=C(NC2=CC=C3N=CSC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C3N=CSC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UAQBBDNWAFULDP-PXNMLYILSA-N 0.000 description 2
- MNGIMRBHILIORK-PXNMLYILSA-N CCOC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=C(Cl)C=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=C(Cl)C=N3)C1=O MNGIMRBHILIORK-PXNMLYILSA-N 0.000 description 2
- UBRRAOXFTDKJKM-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl UBRRAOXFTDKJKM-YBEGLDIGSA-N 0.000 description 2
- OPZWXHJMKMSTIS-WJDWOHSUSA-N CCOC(=O)C1=C(NC2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O OPZWXHJMKMSTIS-WJDWOHSUSA-N 0.000 description 2
- JQQKWMDUIVOUPG-LGMDPLHJSA-N CCOC(=O)C1=C(NCCN2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCCN2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JQQKWMDUIVOUPG-LGMDPLHJSA-N 0.000 description 2
- YHVRQEIRMVDZSM-ZROIWOOFSA-N CCOC(=O)C1=C(NN(C)C(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN(C)C(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YHVRQEIRMVDZSM-ZROIWOOFSA-N 0.000 description 2
- QDYTYNDKOZFOHY-ATVHPVEESA-N CCOC(=O)C1=C(NN(C)C2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN(C)C2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QDYTYNDKOZFOHY-ATVHPVEESA-N 0.000 description 2
- DNTVXDZWVOVLOD-GDNBJRDFSA-N CCOC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DNTVXDZWVOVLOD-GDNBJRDFSA-N 0.000 description 2
- JYEFHIKKSPMYCH-VBKFSLOCSA-N CCOC(=O)C1=C(NN2CCN(CCO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCN(CCO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JYEFHIKKSPMYCH-VBKFSLOCSA-N 0.000 description 2
- YBLJJUGWYINDEB-UVTDQMKNSA-N CCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O Chemical compound CCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O YBLJJUGWYINDEB-UVTDQMKNSA-N 0.000 description 2
- XUYBCVIWMGTAFB-VWKMBWMVSA-N CCOC(=O)C1=C(N[C@H]2CC[C@@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N[C@H]2CC[C@@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XUYBCVIWMGTAFB-VWKMBWMVSA-N 0.000 description 2
- HXVYVGBRCZOKAH-PDGQHHTCSA-N CN(C)CCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CN(C)CCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HXVYVGBRCZOKAH-PDGQHHTCSA-N 0.000 description 2
- CSEZMUPMTDYBIQ-ZDLGFXPLSA-N CN(C)CCOC(=O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CN(C)CCOC(=O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CSEZMUPMTDYBIQ-ZDLGFXPLSA-N 0.000 description 2
- IPTHZBOOJAVUGO-UVTDQMKNSA-N COC(=O)C1=C(N2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(N2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IPTHZBOOJAVUGO-UVTDQMKNSA-N 0.000 description 2
- OKFBKFSERQIYJO-DHDCSXOGSA-N COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O OKFBKFSERQIYJO-DHDCSXOGSA-N 0.000 description 2
- JTZWLVYFQSNAMT-PTNGSMBKSA-N COCCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JTZWLVYFQSNAMT-PTNGSMBKSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 102100034744 Cell division cycle 7-related protein kinase Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- OUXRMEUJNPVXMM-UHFFFAOYSA-N N,n-diethyl-4-piperidinamine Chemical compound CCN(CC)C1CCNCC1 OUXRMEUJNPVXMM-UHFFFAOYSA-N 0.000 description 2
- LEZSYNWRVJOCFC-SHTZXODSSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1N[C@H]1CC[C@H](O)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1N[C@H]1CC[C@H](O)CC1 LEZSYNWRVJOCFC-SHTZXODSSA-N 0.000 description 2
- ZCXOLOPSZIKQTP-ZROIWOOFSA-N O=C(O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound O=C(O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O ZCXOLOPSZIKQTP-ZROIWOOFSA-N 0.000 description 2
- GOTVNNJDJHMLGO-JAIQZWGSSA-N O=C(OC1CCCC(O)C1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OC1CCCC(O)C1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GOTVNNJDJHMLGO-JAIQZWGSSA-N 0.000 description 2
- ZDVDFSVUERABTR-YBEGLDIGSA-N O=C(OCC1CC1)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCC1CC1)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZDVDFSVUERABTR-YBEGLDIGSA-N 0.000 description 2
- XJEZDWMDBJWGGN-ATVHPVEESA-N O=C(OCCCO)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XJEZDWMDBJWGGN-ATVHPVEESA-N 0.000 description 2
- ZLYVSBHEUQGELT-WSVATBPTSA-N O=C1C=C(NC2=CC3=C(C=C2)CN=C3)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC3=C(C=C2)CN=C3)O/C1=C\C1=CNC2=C1C=CC=N2 ZLYVSBHEUQGELT-WSVATBPTSA-N 0.000 description 2
- SGPDQFMEAGAYCC-NDENLUEZSA-N O=C1C=C(NC2=CC=C(N3CCOCC3)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=C(N3CCOCC3)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 SGPDQFMEAGAYCC-NDENLUEZSA-N 0.000 description 2
- FFRPFHKWIHKCQS-SXGWCWSVSA-N O=C1C=C(NC2=CC=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 FFRPFHKWIHKCQS-SXGWCWSVSA-N 0.000 description 2
- SWOMCSZKSHIOFY-YVLHZVERSA-N O=C1C=C(NC2CCCCCC2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2CCCCCC2)O/C1=C\C1=CNC2=C1C=CC=N2 SWOMCSZKSHIOFY-YVLHZVERSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- NQPNRWZEYMSPMJ-UHFFFAOYSA-N butyl 2-(4-fluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCCCC)=C1NC1=CC=C(F)C=C1 NQPNRWZEYMSPMJ-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- VEZUQRBDRNJBJY-UHFFFAOYSA-N cyclohexanone oxime Chemical compound ON=C1CCCCC1 VEZUQRBDRNJBJY-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical compound NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- PKGLAFBARMLJSK-UHFFFAOYSA-N ethyl 2-(2,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C=C1F PKGLAFBARMLJSK-UHFFFAOYSA-N 0.000 description 2
- MSMZAXQJGKGBLR-UHFFFAOYSA-N ethyl 2-(2-hydroxyanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1O MSMZAXQJGKGBLR-UHFFFAOYSA-N 0.000 description 2
- CPYWEFVPCPBVQH-UHFFFAOYSA-N ethyl 2-(4-fluoro-n-methylanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N(C)C1=CC=C(F)C=C1 CPYWEFVPCPBVQH-UHFFFAOYSA-N 0.000 description 2
- RICYDAYYKSMBMP-UHFFFAOYSA-N ethyl 2-(4-hydroxy-2-methylanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(O)C=C1C RICYDAYYKSMBMP-UHFFFAOYSA-N 0.000 description 2
- RDIQGAYEJVIOBO-UHFFFAOYSA-N ethyl 2-(4-methoxyanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OC)C=C1 RDIQGAYEJVIOBO-UHFFFAOYSA-N 0.000 description 2
- ZWMKUFIXYPSMSU-UHFFFAOYSA-N ethyl 2-(7-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CC2=CC(OC)=CC=C2CC1 ZWMKUFIXYPSMSU-UHFFFAOYSA-N 0.000 description 2
- AUZPUOQRGFVNOD-UHFFFAOYSA-N ethyl 2-[2-(2-hydroxyethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCO AUZPUOQRGFVNOD-UHFFFAOYSA-N 0.000 description 2
- VCVGIIZTTFQNLD-UHFFFAOYSA-N ethyl 2-[2-(2-methoxyethoxymethoxy)ethyl-methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(N(C)CCOCOCCOC)OC1=CC1=CNC2=NC=CC=C12 VCVGIIZTTFQNLD-UHFFFAOYSA-N 0.000 description 2
- UJBZUWKRXSHADW-UHFFFAOYSA-N ethyl 2-[2-(2-methoxyethoxymethoxy)ethyl-methylamino]-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(N(C)CCOCOCCOC)OCC1=O UJBZUWKRXSHADW-UHFFFAOYSA-N 0.000 description 2
- RVELKPNAOJZFGF-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(2-pyridin-2-ylethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCC1=CC=CC=N1 RVELKPNAOJZFGF-UHFFFAOYSA-N 0.000 description 2
- VTHLXOZAJIRHBK-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyrimidin-2-ylmethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=NC=CC=N1 VTHLXOZAJIRHBK-UHFFFAOYSA-N 0.000 description 2
- UBDHCGMWOVVKRM-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxyethoxy)-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCO)C=C1C UBDHCGMWOVVKRM-UHFFFAOYSA-N 0.000 description 2
- YJQYFGUPIQMTTE-UHFFFAOYSA-N ethyl 2-[4-(2-methoxyethoxy)-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOC)C=C1C YJQYFGUPIQMTTE-UHFFFAOYSA-N 0.000 description 2
- KHLMFPLDIHUMMI-UHFFFAOYSA-N ethyl 2-[4-(diethylamino)piperidin-1-yl]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCC(N(CC)CC)CC1 KHLMFPLDIHUMMI-UHFFFAOYSA-N 0.000 description 2
- GZVYDHQDGHNYKS-UHFFFAOYSA-N ethyl 2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(NC(=O)OC(C)(C)C)C=C1 GZVYDHQDGHNYKS-UHFFFAOYSA-N 0.000 description 2
- JHBBFPBAVVWGAH-UHFFFAOYSA-N ethyl 2-[4-[(dimethylamino)methyl]-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(CN(C)C)C=C1C JHBBFPBAVVWGAH-UHFFFAOYSA-N 0.000 description 2
- ODJBFSHHCNDWOS-UHFFFAOYSA-N ethyl 2-anilino-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1 ODJBFSHHCNDWOS-UHFFFAOYSA-N 0.000 description 2
- LDOQNLNLIGNFEY-UHFFFAOYSA-N ethyl 4-oxo-2-[[4-(2,2,2-trifluoroethyl)piperazin-1-yl]amino]furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NN1CCN(CC(F)(F)F)CC1 LDOQNLNLIGNFEY-UHFFFAOYSA-N 0.000 description 2
- QBZOONOOZYLGQI-UHFFFAOYSA-N ethyl 4-oxo-2-piperidin-1-ylfuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCCCC1 QBZOONOOZYLGQI-UHFFFAOYSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OKFBKFSERQIYJO-UHFFFAOYSA-N methyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NC1=CC=C(F)C=C1 OKFBKFSERQIYJO-UHFFFAOYSA-N 0.000 description 2
- AYQAMEJKHQBTTR-UHFFFAOYSA-N methyl 2-anilino-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NC1=CC=CC=C1 AYQAMEJKHQBTTR-UHFFFAOYSA-N 0.000 description 2
- MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- JJGBVMJOHGBPJJ-UHFFFAOYSA-N n,n-diethylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.CCN(CC)C1CCNCC1 JJGBVMJOHGBPJJ-UHFFFAOYSA-N 0.000 description 2
- PLFZZZHFLFMZOZ-UHFFFAOYSA-N n,n-dimethyl-1-(3-methyl-4-nitrophenyl)methanamine Chemical compound CN(C)CC1=CC=C([N+]([O-])=O)C(C)=C1 PLFZZZHFLFMZOZ-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- DRAWMFFHIMHSFE-UHFFFAOYSA-N propan-2-yl 2-(morpholin-4-ylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC(C)C)=C1NN1CCOCC1 DRAWMFFHIMHSFE-UHFFFAOYSA-N 0.000 description 2
- KYECCRIGONTHGD-UHFFFAOYSA-N propan-2-yl 2-[4-(2-hydroxyethoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1=CC=C(OCCO)C=C1C KYECCRIGONTHGD-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- SLULEDXETYEYPD-UHFFFAOYSA-N tert-butyl 4-(diethylamino)piperidine-1-carboxylate Chemical compound CCN(CC)C1CCN(C(=O)OC(C)(C)C)CC1 SLULEDXETYEYPD-UHFFFAOYSA-N 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- VCVOSERVUCJNPR-SYDPRGILSA-N (1r,2s)-cyclopentane-1,2-diol Chemical compound O[C@H]1CCC[C@H]1O VCVOSERVUCJNPR-SYDPRGILSA-N 0.000 description 1
- IZUUOHBYLNGVGA-UHFFFAOYSA-N (2-amino-2-oxoethyl) 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC(=O)N)=C1NC1=CC=C(F)C=C1 IZUUOHBYLNGVGA-UHFFFAOYSA-N 0.000 description 1
- LRFWYBZWRQWZIM-UHFFFAOYSA-N (2-fluorophenyl)methanamine Chemical compound NCC1=CC=CC=C1F LRFWYBZWRQWZIM-UHFFFAOYSA-N 0.000 description 1
- KQMQZWLGXVDBHS-UHFFFAOYSA-N (3-hydroxy-2,2-dimethylpropyl) 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC(C)(CO)C)=C1NC1=CC=C(F)C=C1 KQMQZWLGXVDBHS-UHFFFAOYSA-N 0.000 description 1
- GOTVNNJDJHMLGO-UHFFFAOYSA-N (3-hydroxycyclohexyl) 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1C(O)CCCC1OC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 GOTVNNJDJHMLGO-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- JJIJXLCWKOWIBQ-UHFFFAOYSA-N (4-hydroxycyclohexyl) 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC(O)CCC1OC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 JJIJXLCWKOWIBQ-UHFFFAOYSA-N 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- GFPOCAYEKCWFPD-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)piperazine Chemical compound FC(F)(F)CN1CCNCC1 GFPOCAYEKCWFPD-UHFFFAOYSA-N 0.000 description 1
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 1
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
- SOKKPDGDBGAFCB-UHFFFAOYSA-N 1-nitroso-4-(2,2,2-trifluoroethyl)piperazine Chemical compound FC(F)(F)CN1CCN(N=O)CC1 SOKKPDGDBGAFCB-UHFFFAOYSA-N 0.000 description 1
- NYFGIFSPRDNGBT-UHFFFAOYSA-N 1-o-ethyl 3-o-(2-hydroxyethyl) propanedioate Chemical compound CCOC(=O)CC(=O)OCCO NYFGIFSPRDNGBT-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- HNENEALJPWJWJY-UHFFFAOYSA-N 2,4-difluoro-1-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C(F)=C1 HNENEALJPWJWJY-UHFFFAOYSA-N 0.000 description 1
- WDLHXDBUZNLHEG-UHFFFAOYSA-N 2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-5-(quinolin-6-ylamino)furan-3-one Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5C=CC=NC5=CC=4)=CC3=O)=CNC2=N1 WDLHXDBUZNLHEG-UHFFFAOYSA-N 0.000 description 1
- XBXMWCYPNMZTLF-UHFFFAOYSA-N 2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-5-(thiophen-2-ylmethylamino)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NCC1=CC=CS1 XBXMWCYPNMZTLF-UHFFFAOYSA-N 0.000 description 1
- BRMZTMVZRJVMQT-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylic acid Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O)=C1NC1=CC=C(F)C=C1F BRMZTMVZRJVMQT-UHFFFAOYSA-N 0.000 description 1
- XLGVMJXAZRCTRU-UHFFFAOYSA-N 2-(chloromethyl)pyrimidine;hydron;chloride Chemical compound Cl.ClCC1=NC=CC=N1 XLGVMJXAZRCTRU-UHFFFAOYSA-N 0.000 description 1
- CSEZMUPMTDYBIQ-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-(2,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1=CC=C(F)C=C1F CSEZMUPMTDYBIQ-UHFFFAOYSA-N 0.000 description 1
- WUOGMKOVWLTYKX-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1=CC=C(F)C=C1 WUOGMKOVWLTYKX-UHFFFAOYSA-N 0.000 description 1
- DVROGZXCSLSERG-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-(4-methylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC(C)CCN1C(O1)=C(C(=O)OCCN(C)C)C(=O)C1=CC1=CNC2=NC=CC=C12 DVROGZXCSLSERG-UHFFFAOYSA-N 0.000 description 1
- LSDRNABVGGUUAQ-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-(cyclohexylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1CCCCC1 LSDRNABVGGUUAQ-UHFFFAOYSA-N 0.000 description 1
- HXVYVGBRCZOKAH-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1N(C)CC1=CC=CS1 HXVYVGBRCZOKAH-UHFFFAOYSA-N 0.000 description 1
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
- OOZPJQLGAGOGRA-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonyloxy]ethyl 2-(1h-azepin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC(=O)OC(C)(C)C)=C1C1=CC=CC=CN1 OOZPJQLGAGOGRA-UHFFFAOYSA-N 0.000 description 1
- UXBINDLIMILHQI-UHFFFAOYSA-N 2-[2-methyl-4-(2-pyrrolidin-1-ylethylamino)anilino]-4-oxofuran-3-carboxylic acid Chemical compound C=1C=C(NC=2OCC(=O)C=2C(O)=O)C(C)=CC=1NCCN1CCCC1 UXBINDLIMILHQI-UHFFFAOYSA-N 0.000 description 1
- YKQJOOMWCIPRNX-UHFFFAOYSA-N 2-[2-methyl-4-(pyrrolidin-1-ylmethyl)anilino]-4-oxofuran-3-carboxylic acid Chemical compound C=1C=C(NC=2OCC(=O)C=2C(O)=O)C(C)=CC=1CN1CCCC1 YKQJOOMWCIPRNX-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
- ZCXOLOPSZIKQTP-UHFFFAOYSA-N 2-anilino-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylic acid Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O)=C1NC1=CC=CC=C1 ZCXOLOPSZIKQTP-UHFFFAOYSA-N 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
- KLBQTCZOHKZUAB-UHFFFAOYSA-N 2-ethoxycarbonyl-4-hydroxybutanoic acid Chemical compound CCOC(=O)C(C(O)=O)CCO KLBQTCZOHKZUAB-UHFFFAOYSA-N 0.000 description 1
- CMNUAIRJJOJDEB-UHFFFAOYSA-N 2-hydroxyethyl 2-(2-chloroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCO)=C1NC1=CC=CC=C1Cl CMNUAIRJJOJDEB-UHFFFAOYSA-N 0.000 description 1
- YSSHWLBCVUMRSF-UHFFFAOYSA-N 2-hydroxyethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCO)=C1NC1=CC=C(F)C=C1 YSSHWLBCVUMRSF-UHFFFAOYSA-N 0.000 description 1
- VBZSXAIBCOTNSJ-UHFFFAOYSA-N 2-hydroxyethyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCO)=C1NN1CCOCC1 VBZSXAIBCOTNSJ-UHFFFAOYSA-N 0.000 description 1
- JQNHNPVOLVBKPT-UHFFFAOYSA-N 2-hydroxyethyl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OCCOC(=O)C=1C(=O)C(=CC=2C3=CC=CN=C3NC=2)OC=1N(C)CC1=CC=CS1 JQNHNPVOLVBKPT-UHFFFAOYSA-N 0.000 description 1
- POYJXMGSIUWRCZ-UHFFFAOYSA-N 2-methoxyethyl 2-(1h-azepin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1C1=CC=CC=CN1 POYJXMGSIUWRCZ-UHFFFAOYSA-N 0.000 description 1
- CHVRSDUOGFCSIZ-UHFFFAOYSA-N 2-methoxyethyl 2-(2,2-dimethylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCCOC)=C(NN(C)C)OC1=CC1=CNC2=NC=CC=C12 CHVRSDUOGFCSIZ-UHFFFAOYSA-N 0.000 description 1
- HHVAAELVAVJBPM-UHFFFAOYSA-N 2-methoxyethyl 2-(2-chloroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC1=CC=CC=C1Cl HHVAAELVAVJBPM-UHFFFAOYSA-N 0.000 description 1
- IQBTVBSMABYUGK-UHFFFAOYSA-N 2-methoxyethyl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC=C2CN1C(O1)=C(C(=O)OCCOC)C(=O)C1=CC1=CNC2=NC=CC=C12 IQBTVBSMABYUGK-UHFFFAOYSA-N 0.000 description 1
- UMCJTLYFEJYPQN-UHFFFAOYSA-N 2-methoxyethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC1=CC=C(F)C=C1 UMCJTLYFEJYPQN-UHFFFAOYSA-N 0.000 description 1
- AOLFXUGUZKSEOC-UHFFFAOYSA-N 2-methoxyethyl 2-(4-methylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1N1CCC(C)CC1 AOLFXUGUZKSEOC-UHFFFAOYSA-N 0.000 description 1
- JTZWLVYFQSNAMT-UHFFFAOYSA-N 2-methoxyethyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NN1CCOCC1 JTZWLVYFQSNAMT-UHFFFAOYSA-N 0.000 description 1
- AQMBSYLOOCMGRU-UHFFFAOYSA-N 2-methoxyethyl 2-[2-methyl-4-(2-morpholin-4-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC(C(=C1)C)=CC=C1OCCN1CCOCC1 AQMBSYLOOCMGRU-UHFFFAOYSA-N 0.000 description 1
- HBWHCZBKSGOLMV-UHFFFAOYSA-N 2-methoxyethyl 2-[4-(2-hydroxyethylamino)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC1=CC=C(NCCO)C=C1C HBWHCZBKSGOLMV-UHFFFAOYSA-N 0.000 description 1
- JNPJTJUWUIOSQR-UHFFFAOYSA-N 2-methoxyethyl 2-[4-[(dimethylamino)methyl]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC1=CC=C(CN(C)C)C=C1C JNPJTJUWUIOSQR-UHFFFAOYSA-N 0.000 description 1
- NPTDGZSLLHZCBJ-UHFFFAOYSA-N 2-methoxyethyl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1N(C)CC1=CC=CS1 NPTDGZSLLHZCBJ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- BXGYBSJAZFGIPX-UHFFFAOYSA-N 2-pyridin-2-ylethanol Chemical compound OCCC1=CC=CC=N1 BXGYBSJAZFGIPX-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- LVHBTLUNIVKQDX-UHFFFAOYSA-N 3-hydroxypropyl 2-(2,2-dimethylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(NN(C)C)=C(C(=O)OCCCO)C(=O)C1=CC1=CNC2=NC=CC=C12 LVHBTLUNIVKQDX-UHFFFAOYSA-N 0.000 description 1
- VKUNEFVUDFDMNP-UHFFFAOYSA-N 3-hydroxypropyl 2-(2-chloroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCO)=C1NC1=CC=CC=C1Cl VKUNEFVUDFDMNP-UHFFFAOYSA-N 0.000 description 1
- DFGUMJXSVMMIMF-UHFFFAOYSA-N 3-hydroxypropyl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC=C2CN1C(O1)=C(C(=O)OCCCO)C(=O)C1=CC1=CNC2=NC=CC=C12 DFGUMJXSVMMIMF-UHFFFAOYSA-N 0.000 description 1
- LIRLKPYEZYIKOO-UHFFFAOYSA-N 3-hydroxypropyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCO)=C1NC1=CC=C(F)C=C1 LIRLKPYEZYIKOO-UHFFFAOYSA-N 0.000 description 1
- NFZLYLOQWUOWOL-UHFFFAOYSA-N 3-hydroxypropyl 2-(4-methylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC(C)CCN1C(O1)=C(C(=O)OCCCO)C(=O)C1=CC1=CNC2=NC=CC=C12 NFZLYLOQWUOWOL-UHFFFAOYSA-N 0.000 description 1
- XJEZDWMDBJWGGN-UHFFFAOYSA-N 3-hydroxypropyl 2-(cyclohexylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCO)=C1NC1CCCCC1 XJEZDWMDBJWGGN-UHFFFAOYSA-N 0.000 description 1
- ZEFJOMCCBSVJDP-UHFFFAOYSA-N 3-hydroxypropyl 2-[4-(2-hydroxyethylamino)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC1=CC(NCCO)=CC=C1NC(O1)=C(C(=O)OCCCO)C(=O)C1=CC1=CNC2=NC=CC=C12 ZEFJOMCCBSVJDP-UHFFFAOYSA-N 0.000 description 1
- NAPIDBWJKYBFDU-UHFFFAOYSA-N 3-hydroxypropyl 2-[4-[(dimethylamino)methyl]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.CC1=CC(CN(C)C)=CC=C1NC(O1)=C(C(=O)OCCCO)C(=O)C1=CC1=CNC2=NC=CC=C12 NAPIDBWJKYBFDU-UHFFFAOYSA-N 0.000 description 1
- DGZSVBBLLGZHSF-UHFFFAOYSA-N 4,4-diethylpiperidine Chemical compound CCC1(CC)CCNCC1 DGZSVBBLLGZHSF-UHFFFAOYSA-N 0.000 description 1
- AODBGHUVYYWBRL-UHFFFAOYSA-N 4-(aminomethyl)cyclohexan-1-ol Chemical compound NCC1CCC(O)CC1 AODBGHUVYYWBRL-UHFFFAOYSA-N 0.000 description 1
- WOUWGCLQOJPWHS-UHFFFAOYSA-N 4-(bromomethyl)-2-methyl-1-nitrobenzene Chemical compound CC1=CC(CBr)=CC=C1[N+]([O-])=O WOUWGCLQOJPWHS-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- XRRGNLMVTNOFEA-UHFFFAOYSA-N 4-[[4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-2-yl]amino]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 XRRGNLMVTNOFEA-UHFFFAOYSA-N 0.000 description 1
- JHFOWEGCZWLHNW-UHFFFAOYSA-N 4-fluoro-2-methyl-1-nitrobenzene Chemical compound CC1=CC(F)=CC=C1[N+]([O-])=O JHFOWEGCZWLHNW-UHFFFAOYSA-N 0.000 description 1
- XSXLTIGVUOLSGZ-UHFFFAOYSA-N 4-oxo-2-piperidin-1-yl-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylic acid Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O)=C1N1CCCCC1 XSXLTIGVUOLSGZ-UHFFFAOYSA-N 0.000 description 1
- FPEAARFNXIWCTP-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,6-naphthyridine Chemical compound C1=CC=C2CNCCC2=N1 FPEAARFNXIWCTP-UHFFFAOYSA-N 0.000 description 1
- WGEWXQCHLFFUGM-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,6-naphthyridine;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2CNCCC2=N1 WGEWXQCHLFFUGM-UHFFFAOYSA-N 0.000 description 1
- GSMFCPGNCCBTOD-UHFFFAOYSA-N 5-(1-phenylethylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C=1C(=O)C(=CC=2C3=CC=CN=C3NC=2)OC=1NC(C)C1=CC=CC=C1 GSMFCPGNCCBTOD-UHFFFAOYSA-N 0.000 description 1
- SASWFXQWNYXTJT-UHFFFAOYSA-N 5-(1h-indazol-5-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5C=NNC5=CC=4)=CC3=O)=CNC2=N1 SASWFXQWNYXTJT-UHFFFAOYSA-N 0.000 description 1
- UYTPBUYLVLFICC-UHFFFAOYSA-N 5-(1h-pyrazol-5-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC=1C=CNN=1 UYTPBUYLVLFICC-UHFFFAOYSA-N 0.000 description 1
- YWKSBXQXBKBELT-UHFFFAOYSA-N 5-(2,4-difluoroanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound FC1=CC(F)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 YWKSBXQXBKBELT-UHFFFAOYSA-N 0.000 description 1
- JRFALVIUIDOJPN-UHFFFAOYSA-N 5-(2,4-dimethoxyanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound COC1=CC(OC)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 JRFALVIUIDOJPN-UHFFFAOYSA-N 0.000 description 1
- IOVPUSDTYBXUJK-UHFFFAOYSA-N 5-(2,4-dimethylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound CC1=CC(C)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 IOVPUSDTYBXUJK-UHFFFAOYSA-N 0.000 description 1
- QYWMVXVYGUKTID-UHFFFAOYSA-N 5-(2-adamantylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC=C2C(C=C3OC(NC4C5CC6CC(C5)CC4C6)=CC3=O)=CNC2=N1 QYWMVXVYGUKTID-UHFFFAOYSA-N 0.000 description 1
- WVWXGSVOTIYYLF-UHFFFAOYSA-N 5-(2-chloroanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound ClC1=CC=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 WVWXGSVOTIYYLF-UHFFFAOYSA-N 0.000 description 1
- CRCSGMWMCJGAEY-UHFFFAOYSA-N 5-(2-methoxyanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound COC1=CC=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 CRCSGMWMCJGAEY-UHFFFAOYSA-N 0.000 description 1
- VKFIBKFNDCKJFL-UHFFFAOYSA-N 5-(2-methoxyethylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(NCCOC)=CC(=O)C1=CC1=CNC2=NC=CC=C12 VKFIBKFNDCKJFL-UHFFFAOYSA-N 0.000 description 1
- GKDFYJDRBNATEA-UHFFFAOYSA-N 5-(2-phenylpropan-2-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C=1C(=O)C(=CC=2C3=CC=CN=C3NC=2)OC=1NC(C)(C)C1=CC=CC=C1 GKDFYJDRBNATEA-UHFFFAOYSA-N 0.000 description 1
- ZJETYVKMHDIFEH-UHFFFAOYSA-N 5-(3,4-dimethoxyanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=C(OC)C(OC)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 ZJETYVKMHDIFEH-UHFFFAOYSA-N 0.000 description 1
- GYRXCWYLFGWBNW-UHFFFAOYSA-N 5-(3-chloroanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound ClC1=CC=CC(NC=2OC(C(=O)C=2)=CC=2C3=CC=CN=C3NC=2)=C1 GYRXCWYLFGWBNW-UHFFFAOYSA-N 0.000 description 1
- NJLZGPCQAKDOPR-UHFFFAOYSA-N 5-(3h-benzimidazol-5-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5NC=NC5=CC=4)=CC3=O)=CNC2=N1 NJLZGPCQAKDOPR-UHFFFAOYSA-N 0.000 description 1
- RLVRYKARNLJPEV-UHFFFAOYSA-N 5-(4-bromoanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(Br)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 RLVRYKARNLJPEV-UHFFFAOYSA-N 0.000 description 1
- ZBEABLDVTBXNOM-UHFFFAOYSA-N 5-(4-chloroanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(Cl)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 ZBEABLDVTBXNOM-UHFFFAOYSA-N 0.000 description 1
- MHARYXOWQKVLMZ-UHFFFAOYSA-N 5-(4-fluoro-2-methylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound CC1=CC(F)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 MHARYXOWQKVLMZ-UHFFFAOYSA-N 0.000 description 1
- IEPZNIMPOMDPEN-UHFFFAOYSA-N 5-(4-fluoroanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(F)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 IEPZNIMPOMDPEN-UHFFFAOYSA-N 0.000 description 1
- WUDMCCMTZLAUMA-UHFFFAOYSA-N 5-(4-methoxyanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(OC)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 WUDMCCMTZLAUMA-UHFFFAOYSA-N 0.000 description 1
- ITMPBCFOYDXURX-UHFFFAOYSA-N 5-(4-methylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(C)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 ITMPBCFOYDXURX-UHFFFAOYSA-N 0.000 description 1
- SGPDQFMEAGAYCC-UHFFFAOYSA-N 5-(4-morpholin-4-ylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC(C=C1)=CC=C1N1CCOCC1 SGPDQFMEAGAYCC-UHFFFAOYSA-N 0.000 description 1
- ZMENMBCADVVOOH-UHFFFAOYSA-N 5-(4-phenylanilino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC(C=C1)=CC=C1C1=CC=CC=C1 ZMENMBCADVVOOH-UHFFFAOYSA-N 0.000 description 1
- SWOMCSZKSHIOFY-UHFFFAOYSA-N 5-(cycloheptylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC1CCCCCC1 SWOMCSZKSHIOFY-UHFFFAOYSA-N 0.000 description 1
- BXDGIQJPVZDRBS-UHFFFAOYSA-N 5-(cyclopentylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC1CCCC1 BXDGIQJPVZDRBS-UHFFFAOYSA-N 0.000 description 1
- ABUCORORNRDRIL-UHFFFAOYSA-N 5-(cyclopropylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC1CC1 ABUCORORNRDRIL-UHFFFAOYSA-N 0.000 description 1
- SWMJNJLNFGFTHB-UHFFFAOYSA-N 5-(propan-2-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(NC(C)C)=CC(=O)C1=CC1=CNC2=NC=CC=C12 SWMJNJLNFGFTHB-UHFFFAOYSA-N 0.000 description 1
- AWQHDLBFBQMHPS-UHFFFAOYSA-N 5-(pyridin-3-ylamino)-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC1=CC=CN=C1 AWQHDLBFBQMHPS-UHFFFAOYSA-N 0.000 description 1
- YBPGDIPHNUGURW-UHFFFAOYSA-N 5-[(1-methylpiperidin-4-yl)amino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1CN(C)CCC1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 YBPGDIPHNUGURW-UHFFFAOYSA-N 0.000 description 1
- TVVKHXNXBVQVDN-UHFFFAOYSA-N 5-[(2,6-dimethylpyridin-3-yl)amino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound CC1=NC(C)=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 TVVKHXNXBVQVDN-UHFFFAOYSA-N 0.000 description 1
- BAPKTBYTNVHNKC-UHFFFAOYSA-N 5-[(2-fluorophenyl)methylamino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound FC1=CC=CC=C1CNC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 BAPKTBYTNVHNKC-UHFFFAOYSA-N 0.000 description 1
- PDLMXTIGAHGYDL-UHFFFAOYSA-N 5-[(3-fluorophenyl)methylamino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound FC1=CC=CC(CNC=2OC(C(=O)C=2)=CC=2C3=CC=CN=C3NC=2)=C1 PDLMXTIGAHGYDL-UHFFFAOYSA-N 0.000 description 1
- SEFUMBSSKYIYBU-UHFFFAOYSA-N 5-[(3-methylthiophen-2-yl)methylamino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CSC(CNC=2OC(C(=O)C=2)=CC=2C3=CC=CN=C3NC=2)=C1C SEFUMBSSKYIYBU-UHFFFAOYSA-N 0.000 description 1
- PRDAOPGPHPDLMU-UHFFFAOYSA-N 5-[(4-fluorophenyl)methylamino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound C1=CC(F)=CC=C1CNC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 PRDAOPGPHPDLMU-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- HSLBRNLNLFIWCY-UHFFFAOYSA-N 5-[2-(2-hydroxyethoxy)anilino]-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound OCCOC1=CC=CC=C1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 HSLBRNLNLFIWCY-UHFFFAOYSA-N 0.000 description 1
- FFRPFHKWIHKCQS-UHFFFAOYSA-N 5-anilino-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-one Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C=C1NC1=CC=CC=C1 FFRPFHKWIHKCQS-UHFFFAOYSA-N 0.000 description 1
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BJPDAUDWJMRYGO-LCYFTJDESA-N C#CCNC1=C(C(=O)OCC)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound C#CCNC1=C(C(=O)OCC)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 BJPDAUDWJMRYGO-LCYFTJDESA-N 0.000 description 1
- DMAWPXFDXICPKM-UHFFFAOYSA-N C(C)(=O)O.N1C=C(C=2C1=NC=CC2)C=C2C(C(=C(O2)NC2=C(C=C(C=C2)NCCO)C)C(=O)OCCN(C)C)=O Chemical compound C(C)(=O)O.N1C=C(C=2C1=NC=CC2)C=C2C(C(=C(O2)NC2=C(C=C(C=C2)NCCO)C)C(=O)OCCN(C)C)=O DMAWPXFDXICPKM-UHFFFAOYSA-N 0.000 description 1
- BEYKRASJJSZRMH-PNCOJPCNSA-N C.CC(=O)O.CCOC(=O)C1=C(N2CCCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound C.CC(=O)O.CCOC(=O)C1=C(N2CCCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BEYKRASJJSZRMH-PNCOJPCNSA-N 0.000 description 1
- INVQAQMXPPHMDP-AZJSCORLSA-N C.CC(C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound C.CC(C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O INVQAQMXPPHMDP-AZJSCORLSA-N 0.000 description 1
- NMPOHDZMFJLFRM-JCTPKUEWSA-N C.CCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound C.CCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NMPOHDZMFJLFRM-JCTPKUEWSA-N 0.000 description 1
- FOMWFLWYPGJPEM-UHFFFAOYSA-N C1CC(C(=CC=C2)OC)=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 Chemical compound C1CC(C(=CC=C2)OC)=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 FOMWFLWYPGJPEM-UHFFFAOYSA-N 0.000 description 1
- LXXOJAGCKNZMQF-UHFFFAOYSA-N C1CC2=CC(OC)=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 Chemical compound C1CC2=CC(OC)=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 LXXOJAGCKNZMQF-UHFFFAOYSA-N 0.000 description 1
- HJOJKOWBSSWCBP-UHFFFAOYSA-N C1CCC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 Chemical compound C1CCC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 HJOJKOWBSSWCBP-UHFFFAOYSA-N 0.000 description 1
- BSAHCFNRGMVIFP-OTUCAILMSA-N C1CCCCCC1.CCOC(=O)C1=C(N)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound C1CCCCCC1.CCOC(=O)C1=C(N)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BSAHCFNRGMVIFP-OTUCAILMSA-N 0.000 description 1
- DBLDLYUVJGDMMD-UHFFFAOYSA-N C1COC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 Chemical compound C1COC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 DBLDLYUVJGDMMD-UHFFFAOYSA-N 0.000 description 1
- ZDVDFSVUERABTR-UHFFFAOYSA-N C1COCCN1NC=1OC(=CC=2C3=CC=CN=C3NC=2)C(=O)C=1C(=O)OCC1CC1 Chemical compound C1COCCN1NC=1OC(=CC=2C3=CC=CN=C3NC=2)C(=O)C=1C(=O)OCC1CC1 ZDVDFSVUERABTR-UHFFFAOYSA-N 0.000 description 1
- CWBCVKHGWWNUSU-JOCQHMNTSA-N C1C[C@@H](O)CC[C@@H]1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 Chemical compound C1C[C@@H](O)CC[C@@H]1NC(O1)=CC(=O)C1=CC1=CNC2=NC=CC=C12 CWBCVKHGWWNUSU-JOCQHMNTSA-N 0.000 description 1
- VIIOXRGMSNPPGS-JAIQZWGSSA-N CC(=O)O.CC(C)OC(=O)C1=C(N2CCC3=C(C=C(Cl)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CC(C)OC(=O)C1=C(N2CCC3=C(C=C(Cl)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VIIOXRGMSNPPGS-JAIQZWGSSA-N 0.000 description 1
- KHTNFSCBXKXWNV-STZFKDTASA-N CC(=O)O.CC1=C(NC2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(NCCO)=C1 Chemical compound CC(=O)O.CC1=C(NC2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(NCCO)=C1 KHTNFSCBXKXWNV-STZFKDTASA-N 0.000 description 1
- GCLLJSJIYGVCTI-MTJSOVHGSA-N CC(=O)O.CC1=CC(CN(C)C)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC(=O)O.CC1=CC(CN(C)C)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 GCLLJSJIYGVCTI-MTJSOVHGSA-N 0.000 description 1
- KEGSUNNUOQIPEW-MTJSOVHGSA-N CC(=O)O.CC1=CC2=C(C=C1)CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 Chemical compound CC(=O)O.CC1=CC2=C(C=C1)CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 KEGSUNNUOQIPEW-MTJSOVHGSA-N 0.000 description 1
- XXCOSWSENVGTTI-VBKFSLOCSA-N CC(=O)O.CCOC(=O)C1=C(N2CCCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(N2CCCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XXCOSWSENVGTTI-VBKFSLOCSA-N 0.000 description 1
- DIZUJSPSTJLLHV-ULJHMMPZSA-N CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DIZUJSPSTJLLHV-ULJHMMPZSA-N 0.000 description 1
- NAXPVQRFGLOQPJ-KQWNVCNZSA-N CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(NCCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(NCCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NAXPVQRFGLOQPJ-KQWNVCNZSA-N 0.000 description 1
- ZBDYXWWPAHPXAK-KQWNVCNZSA-N CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN(CC)CC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN(CC)CC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZBDYXWWPAHPXAK-KQWNVCNZSA-N 0.000 description 1
- CSKNOBGKYACPRG-KQWNVCNZSA-N CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CSKNOBGKYACPRG-KQWNVCNZSA-N 0.000 description 1
- WJWMWGRAOJEASD-ULJHMMPZSA-N CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O WJWMWGRAOJEASD-ULJHMMPZSA-N 0.000 description 1
- PHGXEJVPJKSOQN-UVTDQMKNSA-N CC(=O)O.CN(C)CCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CN(C)CCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PHGXEJVPJKSOQN-UVTDQMKNSA-N 0.000 description 1
- JURUSWPLLJLNQH-VBKFSLOCSA-N CC(=O)O.CN(C)CCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.CN(C)CCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JURUSWPLLJLNQH-VBKFSLOCSA-N 0.000 description 1
- DTENVFQQYOVNCU-ULJHMMPZSA-N CC(=O)O.COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCCC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCCC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DTENVFQQYOVNCU-ULJHMMPZSA-N 0.000 description 1
- YARVZOIAUJXSJG-BWAHOGKJSA-N CC(=O)O.COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCN(C)CC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(=O)O.COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCN(C)CC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YARVZOIAUJXSJG-BWAHOGKJSA-N 0.000 description 1
- CVPPVILRKGBUDS-CYVLTUHYSA-N CC(C)(C)OC(=O)OCCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O Chemical compound CC(C)(C)OC(=O)OCCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O CVPPVILRKGBUDS-CYVLTUHYSA-N 0.000 description 1
- KQMQZWLGXVDBHS-ZDLGFXPLSA-N CC(C)(CO)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)(CO)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O KQMQZWLGXVDBHS-ZDLGFXPLSA-N 0.000 description 1
- UKNSDRUWZAASLO-GRSHGNNSSA-N CC(C)C1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CC(C)C1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 UKNSDRUWZAASLO-GRSHGNNSSA-N 0.000 description 1
- KQBQECFODLFPNU-LFYAFSDUSA-N CC(C)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CC(C)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO KQBQECFODLFPNU-LFYAFSDUSA-N 0.000 description 1
- CYDUVYPWCHUYHA-YBEGLDIGSA-N CC(C)COC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)COC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CYDUVYPWCHUYHA-YBEGLDIGSA-N 0.000 description 1
- SWMJNJLNFGFTHB-MLPAPPSSSA-N CC(C)NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC(C)NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 SWMJNJLNFGFTHB-MLPAPPSSSA-N 0.000 description 1
- QLUMGICXACFOCQ-YVLHZVERSA-N CC(C)OC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QLUMGICXACFOCQ-YVLHZVERSA-N 0.000 description 1
- DWWSKMAGQCADBD-JAIQZWGSSA-N CC(C)OC(=O)C1=C(N2CCC3=C(C=C(F)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(N2CCC3=C(C=C(F)C=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DWWSKMAGQCADBD-JAIQZWGSSA-N 0.000 description 1
- AXEKWDKNOSUFRH-NDENLUEZSA-N CC(C)OC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AXEKWDKNOSUFRH-NDENLUEZSA-N 0.000 description 1
- XBABQPJGOZBTCS-ATVHPVEESA-N CC(C)OC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=C\NC3=NC=CC=C32)C1=O Chemical compound CC(C)OC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=C\NC3=NC=CC=C32)C1=O XBABQPJGOZBTCS-ATVHPVEESA-N 0.000 description 1
- VSYRFYZXANWBTR-YVLHZVERSA-N CC(C)OC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VSYRFYZXANWBTR-YVLHZVERSA-N 0.000 description 1
- AHWZPJUJQZBTJU-ZSOIEALJSA-N CC(C)OC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AHWZPJUJQZBTJU-ZSOIEALJSA-N 0.000 description 1
- HVOLDEWHMOJLTC-BOPFTXTBSA-N CC(C)OC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HVOLDEWHMOJLTC-BOPFTXTBSA-N 0.000 description 1
- SQTLKVDNMQOIAM-YBEGLDIGSA-N CC(C)OC(=O)C1=C(NC2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NC2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O SQTLKVDNMQOIAM-YBEGLDIGSA-N 0.000 description 1
- LZUJXJMFQJESST-JYRVWZFOSA-N CC(C)OC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LZUJXJMFQJESST-JYRVWZFOSA-N 0.000 description 1
- VIIFLQJEKHVDMB-YBEGLDIGSA-N CC(C)OC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NN2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VIIFLQJEKHVDMB-YBEGLDIGSA-N 0.000 description 1
- ZYJVGRGVTYFMJJ-GDNBJRDFSA-N CC(C)OC(=O)C1=C(NN2CCS(=O)(=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(NN2CCS(=O)(=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZYJVGRGVTYFMJJ-GDNBJRDFSA-N 0.000 description 1
- LEZSYNWRVJOCFC-HJGBLPHTSA-N CC(C)OC(=O)C1=C(N[C@H]2CC[C@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC(C)OC(=O)C1=C(N[C@H]2CC[C@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LEZSYNWRVJOCFC-HJGBLPHTSA-N 0.000 description 1
- WLEDQNAXUWCFPE-ITYLOYPMSA-N CC1=C(C2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(C#CCN2CCN(C)CC2)=C1 Chemical compound CC1=C(C2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(C#CCN2CCN(C)CC2)=C1 WLEDQNAXUWCFPE-ITYLOYPMSA-N 0.000 description 1
- CBIDXRUQWBAKIU-BKUYFWCQSA-N CC1=C(NC2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(CN(C)C)=C1.Cl Chemical compound CC1=C(NC2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(CN(C)C)=C1.Cl CBIDXRUQWBAKIU-BKUYFWCQSA-N 0.000 description 1
- ZEFJOMCCBSVJDP-MOSHPQCFSA-N CC1=C(NC2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(NCCO)=C1 Chemical compound CC1=C(NC2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(NCCO)=C1 ZEFJOMCCBSVJDP-MOSHPQCFSA-N 0.000 description 1
- MHARYXOWQKVLMZ-IUXPMGMMSA-N CC1=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(F)=C1 Chemical compound CC1=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=CC(F)=C1 MHARYXOWQKVLMZ-IUXPMGMMSA-N 0.000 description 1
- GOHCVRPCQGHNJD-NDENLUEZSA-N CC1=CC(NCCO)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(NCCO)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 GOHCVRPCQGHNJD-NDENLUEZSA-N 0.000 description 1
- YIWQHQIRMFXHGW-YDHFHHHVSA-N CC1=CC(OCCN(C)C)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1.O=CO Chemical compound CC1=CC(OCCN(C)C)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1.O=CO YIWQHQIRMFXHGW-YDHFHHHVSA-N 0.000 description 1
- WXJWUAFUIRHOSJ-BJMORVNCSA-N CC1=CC(OCCN(C)C)=CC=C1NC1=C(C(=O)OCC2CC2)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1.O=CO Chemical compound CC1=CC(OCCN(C)C)=CC=C1NC1=C(C(=O)OCC2CC2)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1.O=CO WXJWUAFUIRHOSJ-BJMORVNCSA-N 0.000 description 1
- FIYKOZJRHPUQFY-JLPGSUDCSA-N CC1=CC(OCCN2CCCC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(OCCN2CCCC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 FIYKOZJRHPUQFY-JLPGSUDCSA-N 0.000 description 1
- DJIZWVOKKRMMHB-UQQQWYQISA-N CC1=CC(OCCN2CCN(C)CC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(OCCN2CCN(C)CC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 DJIZWVOKKRMMHB-UQQQWYQISA-N 0.000 description 1
- VBMOQYHTRXJUKN-JLPGSUDCSA-N CC1=CC(OCCN2CCOCC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(OCCN2CCOCC2)=CC=C1NC1=C(C(=O)OC(C)C)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 VBMOQYHTRXJUKN-JLPGSUDCSA-N 0.000 description 1
- GOOVIHZLFJFQPG-MTJSOVHGSA-N CC1=CC(OCCO)=CC=C1NC1=C(C(=O)OCC2CC2)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CC1=CC(OCCO)=CC=C1NC1=C(C(=O)OCC2CC2)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 GOOVIHZLFJFQPG-MTJSOVHGSA-N 0.000 description 1
- ITMPBCFOYDXURX-MFOYZWKCSA-N CC1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CC1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 ITMPBCFOYDXURX-MFOYZWKCSA-N 0.000 description 1
- TVVKHXNXBVQVDN-IUXPMGMMSA-N CC1=NC(C)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CC1=NC(C)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 TVVKHXNXBVQVDN-IUXPMGMMSA-N 0.000 description 1
- BZWUHTCGLOAOCU-BOPFTXTBSA-N CC1CCN(C2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 Chemical compound CC1CCN(C2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 BZWUHTCGLOAOCU-BOPFTXTBSA-N 0.000 description 1
- NFZLYLOQWUOWOL-ATVHPVEESA-N CC1CCN(C2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 Chemical compound CC1CCN(C2=C(C(=O)OCCCO)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 NFZLYLOQWUOWOL-ATVHPVEESA-N 0.000 description 1
- DVROGZXCSLSERG-AQTBWJFISA-N CC1CCN(C2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 Chemical compound CC1CCN(C2=C(C(=O)OCCN(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 DVROGZXCSLSERG-AQTBWJFISA-N 0.000 description 1
- ABEGWRABXMPHPY-PDGQHHTCSA-N CCCCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCCCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ABEGWRABXMPHPY-PDGQHHTCSA-N 0.000 description 1
- JBCFIQFWUOLNRR-YGCQTIHHSA-N CCCCOC(=O)C1=C(NC2=CC=C(OCCN(C)C)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CCCCOC(=O)C1=C(NC2=CC=C(OCCN(C)C)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO JBCFIQFWUOLNRR-YGCQTIHHSA-N 0.000 description 1
- CTDMIIHLYDCSHI-STZFKDTASA-N CCCCOC(=O)C1=C(NC2=CC=C(OCCO)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCCCOC(=O)C1=C(NC2=CC=C(OCCO)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CTDMIIHLYDCSHI-STZFKDTASA-N 0.000 description 1
- KRHNYBNFDBZKBC-MOSHPQCFSA-N CCCNC1=CC(C)=C(NC2=C(C(=O)OCC)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CCCNC1=CC(C)=C(NC2=C(C(=O)OCC)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 KRHNYBNFDBZKBC-MOSHPQCFSA-N 0.000 description 1
- RSUFWHHFWMZUOV-PTNGSMBKSA-N CCCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCCOC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RSUFWHHFWMZUOV-PTNGSMBKSA-N 0.000 description 1
- NBFALLAVNYGPDB-BKUYFWCQSA-N CCCOC1=CC=C(NC2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C(C)=C1 Chemical compound CCCOC1=CC=C(NC2=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C(C)=C1 NBFALLAVNYGPDB-BKUYFWCQSA-N 0.000 description 1
- OWUBZGOQVWTWON-UYRXBGFRSA-N CCCOC1=CC=C(NC2=C(C(=O)OCC)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound CCCOC1=CC=C(NC2=C(C(=O)OCC)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 OWUBZGOQVWTWON-UYRXBGFRSA-N 0.000 description 1
- YVVKLDSSNAZKOB-WQLSENKSSA-N CCNC1=C(C(=O)OCC)C(=O)/C(=C/C2=C/NC3=C2C=CC=N3)O1.Cl Chemical compound CCNC1=C(C(=O)OCC)C(=O)/C(=C/C2=C/NC3=C2C=CC=N3)O1.Cl YVVKLDSSNAZKOB-WQLSENKSSA-N 0.000 description 1
- QUHQFAFGAQJHHZ-BKUYFWCQSA-N CCOC(=O)C1=C(C2CCC3=C(C2)C(OC)=CC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(C2CCC3=C(C2)C(OC)=CC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QUHQFAFGAQJHHZ-BKUYFWCQSA-N 0.000 description 1
- YZNQXAGFQMABLU-WQRHYEAKSA-N CCOC(=O)C1=C(CC2=CC=C(Cl)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(CC2=CC=C(Cl)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O YZNQXAGFQMABLU-WQRHYEAKSA-N 0.000 description 1
- GAOKOSOHNPDIBQ-WQRHYEAKSA-N CCOC(=O)C1=C(CC2=CC=CC(Cl)=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(CC2=CC=CC(Cl)=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O GAOKOSOHNPDIBQ-WQRHYEAKSA-N 0.000 description 1
- RWKFYCGLQHBFTI-BOPFTXTBSA-N CCOC(=O)C1=C(N(C)C2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(N(C)C2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl RWKFYCGLQHBFTI-BOPFTXTBSA-N 0.000 description 1
- RTUIIVQPVVJWJQ-ATVHPVEESA-N CCOC(=O)C1=C(N(C)C2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)C2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RTUIIVQPVVJWJQ-ATVHPVEESA-N 0.000 description 1
- KNOZUKZXQAEMBE-LCYFTJDESA-N CCOC(=O)C1=C(N(C)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O KNOZUKZXQAEMBE-LCYFTJDESA-N 0.000 description 1
- DYXDJLMDJMZVPI-PDGQHHTCSA-N CCOC(=O)C1=C(N(C)CC2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)CC2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DYXDJLMDJMZVPI-PDGQHHTCSA-N 0.000 description 1
- DEGQIXSYBNOYMK-YBEGLDIGSA-N CCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DEGQIXSYBNOYMK-YBEGLDIGSA-N 0.000 description 1
- LHRNVGZSUKQCSU-PNCOJPCNSA-N CCOC(=O)C1=C(N(C)CCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CCOC(=O)C1=C(N(C)CCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO LHRNVGZSUKQCSU-PNCOJPCNSA-N 0.000 description 1
- LVAJHQWZVYRGFJ-LCYFTJDESA-N CCOC(=O)C1=C(N(C)CCO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)CCO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LVAJHQWZVYRGFJ-LCYFTJDESA-N 0.000 description 1
- VCVGIIZTTFQNLD-ATVHPVEESA-N CCOC(=O)C1=C(N(C)CCOCOCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(C)CCOCOCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VCVGIIZTTFQNLD-ATVHPVEESA-N 0.000 description 1
- OVHASMXVOGHVJI-UVTDQMKNSA-N CCOC(=O)C1=C(N(CC)CC)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(N(CC)CC)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl OVHASMXVOGHVJI-UVTDQMKNSA-N 0.000 description 1
- LWUNIWLNIYIKCA-VBKFSLOCSA-N CCOC(=O)C1=C(N(CCOC)CCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N(CCOC)CCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LWUNIWLNIYIKCA-VBKFSLOCSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-MFOYZWKCSA-N CCOC(=O)C1=C(N2CC(C)CC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CC(C)CC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YUYFSQWXJPLOEZ-MFOYZWKCSA-N 0.000 description 1
- BDLOOGGKJOBMIB-PXNMLYILSA-N CCOC(=O)C1=C(N2CC(C)OC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CC(C)OC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BDLOOGGKJOBMIB-PXNMLYILSA-N 0.000 description 1
- VLPKKRQAXGIEIC-ZDLGFXPLSA-N CCOC(=O)C1=C(N2CC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VLPKKRQAXGIEIC-ZDLGFXPLSA-N 0.000 description 1
- FKEBEPKKNMVZFC-WJDWOHSUSA-N CCOC(=O)C1=C(N2CCC(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FKEBEPKKNMVZFC-WJDWOHSUSA-N 0.000 description 1
- GBZVNTRVQGEFEJ-YBEGLDIGSA-N CCOC(=O)C1=C(N2CCC(CO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(CO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GBZVNTRVQGEFEJ-YBEGLDIGSA-N 0.000 description 1
- DNGDWUPAMOAANK-ATVHPVEESA-N CCOC(=O)C1=C(N2CCC(N(C)C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(N(C)C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DNGDWUPAMOAANK-ATVHPVEESA-N 0.000 description 1
- FHTDIJZGIBFLLX-HKWRFOASSA-N CCOC(=O)C1=C(N2CCC(N(C)CCN(C)C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(N(C)CCN(C)C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FHTDIJZGIBFLLX-HKWRFOASSA-N 0.000 description 1
- FSWUCHGDPFIGOH-RGEXLXHISA-N CCOC(=O)C1=C(N2CCC(N(CC)CC)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(N(CC)CC)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FSWUCHGDPFIGOH-RGEXLXHISA-N 0.000 description 1
- PCNKTIHZRTXCPA-RGEXLXHISA-N CCOC(=O)C1=C(N2CCC(N3CCOCC3)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(N3CCOCC3)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PCNKTIHZRTXCPA-RGEXLXHISA-N 0.000 description 1
- IKZIAXLUHZJYRP-GDNBJRDFSA-N CCOC(=O)C1=C(N2CCC(O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC(O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IKZIAXLUHZJYRP-GDNBJRDFSA-N 0.000 description 1
- HXYKJEKKQIDIPL-VVTVMFAVSA-N CCOC(=O)C1=C(N2CCC3=C(C2)N=CC=C3)O/C(=C\C2=CNC3=NC=CC=C23)C1=O.O=CO Chemical compound CCOC(=O)C1=C(N2CCC3=C(C2)N=CC=C3)O/C(=C\C2=CNC3=NC=CC=C23)C1=O.O=CO HXYKJEKKQIDIPL-VVTVMFAVSA-N 0.000 description 1
- INVQNWGZEHEYMW-UNOMPAQXSA-N CCOC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O INVQNWGZEHEYMW-UNOMPAQXSA-N 0.000 description 1
- FOMWFLWYPGJPEM-NDENLUEZSA-N CCOC(=O)C1=C(N2CCC3=C(C=CC=C3OC)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C(C=CC=C3OC)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FOMWFLWYPGJPEM-NDENLUEZSA-N 0.000 description 1
- DOUVXIVMJMSKLI-VVTVMFAVSA-N CCOC(=O)C1=C(N2CCC3=C(C=CC=N3)C2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O.O=CO Chemical compound CCOC(=O)C1=C(N2CCC3=C(C=CC=N3)C2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O.O=CO DOUVXIVMJMSKLI-VVTVMFAVSA-N 0.000 description 1
- FDRVCSJVBKGQTR-PDGQHHTCSA-N CCOC(=O)C1=C(N2CCC3=C2C=CC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCC3=C2C=CC=C3)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FDRVCSJVBKGQTR-PDGQHHTCSA-N 0.000 description 1
- CZSOHNKWYXDPSI-DHDCSXOGSA-N CCOC(=O)C1=C(N2CCCC(C(N)=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC(C(N)=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CZSOHNKWYXDPSI-DHDCSXOGSA-N 0.000 description 1
- NDQIDZYOKPEFKN-WJDWOHSUSA-N CCOC(=O)C1=C(N2CCCC(C)(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC(C)(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NDQIDZYOKPEFKN-WJDWOHSUSA-N 0.000 description 1
- LFEMLCQDCATYTP-YBEGLDIGSA-N CCOC(=O)C1=C(N2CCCC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC(C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LFEMLCQDCATYTP-YBEGLDIGSA-N 0.000 description 1
- ODPUNLAWIUSDRN-SXGWCWSVSA-N CCOC(=O)C1=C(N2CCCC(CO)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC(CO)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ODPUNLAWIUSDRN-SXGWCWSVSA-N 0.000 description 1
- IMUYQEGREJCUGE-DHDCSXOGSA-N CCOC(=O)C1=C(N2CCCC(O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC(O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IMUYQEGREJCUGE-DHDCSXOGSA-N 0.000 description 1
- ZFMFAMDHTOJVQU-UVTDQMKNSA-N CCOC(=O)C1=C(N2CCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(N2CCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl ZFMFAMDHTOJVQU-UVTDQMKNSA-N 0.000 description 1
- HJOJKOWBSSWCBP-MOSHPQCFSA-N CCOC(=O)C1=C(N2CCCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HJOJKOWBSSWCBP-MOSHPQCFSA-N 0.000 description 1
- UNGVRAYQPPZUHH-PTNGSMBKSA-N CCOC(=O)C1=C(N2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O UNGVRAYQPPZUHH-PTNGSMBKSA-N 0.000 description 1
- NPUZYXDHCZOSHA-YBEGLDIGSA-N CCOC(=O)C1=C(N2CCCCC2CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCCC2CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NPUZYXDHCZOSHA-YBEGLDIGSA-N 0.000 description 1
- PDSQYYUYIBSZIT-MOSHPQCFSA-N CCOC(=O)C1=C(N2CCCCC2COCOCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCCC2COCOCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PDSQYYUYIBSZIT-MOSHPQCFSA-N 0.000 description 1
- GEQOWMZBUSACNR-VBKFSLOCSA-N CCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GEQOWMZBUSACNR-VBKFSLOCSA-N 0.000 description 1
- VJGJCWJLDRNURJ-ATVHPVEESA-N CCOC(=O)C1=C(N2CCCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VJGJCWJLDRNURJ-ATVHPVEESA-N 0.000 description 1
- FEPRRKQKIZUSKK-PTNGSMBKSA-N CCOC(=O)C1=C(N2CCCNCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCCNCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FEPRRKQKIZUSKK-PTNGSMBKSA-N 0.000 description 1
- AGTSYZAWOLJQLX-WJDWOHSUSA-N CCOC(=O)C1=C(N2CCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AGTSYZAWOLJQLX-WJDWOHSUSA-N 0.000 description 1
- SRKBAJNQSLWEGU-PTNGSMBKSA-N CCOC(=O)C1=C(N2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(N2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl SRKBAJNQSLWEGU-PTNGSMBKSA-N 0.000 description 1
- QULDPGALDVOIHD-GDNBJRDFSA-N CCOC(=O)C1=C(N2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCN(CC(F)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QULDPGALDVOIHD-GDNBJRDFSA-N 0.000 description 1
- FWQRZBQNFLWDEY-VBKFSLOCSA-N CCOC(=O)C1=C(N2CCN(CCO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCN(CCO)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FWQRZBQNFLWDEY-VBKFSLOCSA-N 0.000 description 1
- VEBIKBAGNOQLGS-JYRVWZFOSA-N CCOC(=O)C1=C(N2CCNC(=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCNC(=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VEBIKBAGNOQLGS-JYRVWZFOSA-N 0.000 description 1
- UOXAFOWNFMYCKW-UNOMPAQXSA-N CCOC(=O)C1=C(N2CCNC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCNC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UOXAFOWNFMYCKW-UNOMPAQXSA-N 0.000 description 1
- LMXVZPYCHKDODF-UVTDQMKNSA-N CCOC(=O)C1=C(N2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LMXVZPYCHKDODF-UVTDQMKNSA-N 0.000 description 1
- ZMTLYAPELCLAQU-UVTDQMKNSA-N CCOC(=O)C1=C(N2CCS(=O)(=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCS(=O)(=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZMTLYAPELCLAQU-UVTDQMKNSA-N 0.000 description 1
- DIDUNUVUNGLZLU-PDGQHHTCSA-N CCOC(=O)C1=C(N2CCSC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCSC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DIDUNUVUNGLZLU-PDGQHHTCSA-N 0.000 description 1
- YCZPJAOVFOJXLU-UVTDQMKNSA-N CCOC(=O)C1=C(N2CCSCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2CCSCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YCZPJAOVFOJXLU-UVTDQMKNSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-KFWDLZQKSA-N CCOC(=O)C1=C(N2C[C@@H](C)C[C@@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2C[C@@H](C)C[C@@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YUYFSQWXJPLOEZ-KFWDLZQKSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-RGQRQWOTSA-N CCOC(=O)C1=C(N2C[C@@H](C)C[C@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N2C[C@@H](C)C[C@H](C)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YUYFSQWXJPLOEZ-RGQRQWOTSA-N 0.000 description 1
- GRZMSOHEDNGQIF-AQTBWJFISA-N CCOC(=O)C1=C(NC(C)(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC(C)(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GRZMSOHEDNGQIF-AQTBWJFISA-N 0.000 description 1
- FYXCKVOSHRZQPF-JYRVWZFOSA-N CCOC(=O)C1=C(NC(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FYXCKVOSHRZQPF-JYRVWZFOSA-N 0.000 description 1
- LUPMYBRJNMJYJT-PDGQHHTCSA-N CCOC(=O)C1=C(NC(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LUPMYBRJNMJYJT-PDGQHHTCSA-N 0.000 description 1
- JGGIYSNTQLQSGE-QPEQYQDCSA-N CCOC(=O)C1=C(NC(C)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC(C)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JGGIYSNTQLQSGE-QPEQYQDCSA-N 0.000 description 1
- FNZGOLDUKPRIBS-MLPAPPSSSA-N CCOC(=O)C1=C(NC(CO)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC(CO)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FNZGOLDUKPRIBS-MLPAPPSSSA-N 0.000 description 1
- NBUZPOPTANVLMD-JCMHNJIXSA-N CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NBUZPOPTANVLMD-JCMHNJIXSA-N 0.000 description 1
- AAMVQWXBOZRKPY-UQQQWYQISA-N CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AAMVQWXBOZRKPY-UQQQWYQISA-N 0.000 description 1
- RFCAXZDEWUMKKB-IJVOEZGUSA-N CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(C#CCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO RFCAXZDEWUMKKB-IJVOEZGUSA-N 0.000 description 1
- RVXJQZUIMMXUOK-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(C#CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(C#CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RVXJQZUIMMXUOK-MOSHPQCFSA-N 0.000 description 1
- BNRXOZGYCGMTNM-WQRHYEAKSA-N CCOC(=O)C1=C(NC2=C(C)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BNRXOZGYCGMTNM-WQRHYEAKSA-N 0.000 description 1
- HVSZNKCXHKZIKQ-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CC#N)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CC#N)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HVSZNKCXHKZIKQ-UNOMPAQXSA-N 0.000 description 1
- FJMGSXWFYPSVPN-YNYSCKANSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO FJMGSXWFYPSVPN-YNYSCKANSA-N 0.000 description 1
- NTFGMTBQNVRERX-STZFKDTASA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NTFGMTBQNVRERX-STZFKDTASA-N 0.000 description 1
- IHGBHCIBLCKJDZ-JLPGSUDCSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IHGBHCIBLCKJDZ-JLPGSUDCSA-N 0.000 description 1
- BIBDMJYHPVEIMT-KQWNVCNZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BIBDMJYHPVEIMT-KQWNVCNZSA-N 0.000 description 1
- AZDFVHOCZFBOCS-ULJHMMPZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AZDFVHOCZFBOCS-ULJHMMPZSA-N 0.000 description 1
- MEZZKMFTILRQIP-KQWNVCNZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MEZZKMFTILRQIP-KQWNVCNZSA-N 0.000 description 1
- SJHVOQSIOMGCOB-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O SJHVOQSIOMGCOB-UNOMPAQXSA-N 0.000 description 1
- HZRQNQAHLAFCBG-NDENLUEZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HZRQNQAHLAFCBG-NDENLUEZSA-N 0.000 description 1
- QAGKKTZNVIYCSX-UCQKPKSFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCC(O)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QAGKKTZNVIYCSX-UCQKPKSFSA-N 0.000 description 1
- MOYLYCWMMDNEKC-HMAPJEAMSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MOYLYCWMMDNEKC-HMAPJEAMSA-N 0.000 description 1
- REYPFEXPHPGXNJ-XYGWBWBKSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCN(C(C)C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCN(C(C)C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O REYPFEXPHPGXNJ-XYGWBWBKSA-N 0.000 description 1
- PPJGPXWILAGSLJ-HAHDFKILSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCN(C)CC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PPJGPXWILAGSLJ-HAHDFKILSA-N 0.000 description 1
- PMLBRMAZXOJCMB-HMAPJEAMSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PMLBRMAZXOJCMB-HMAPJEAMSA-N 0.000 description 1
- GKMZQWVRMFWAOA-MTJSOVHGSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CNC(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CNC(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GKMZQWVRMFWAOA-MTJSOVHGSA-N 0.000 description 1
- HPZRJNZNFXISMN-ODLFYWEKSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CNC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CNC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HPZRJNZNFXISMN-ODLFYWEKSA-N 0.000 description 1
- MRTXRTNMMVWDLI-UCQKPKSFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(CNC3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(CNC3CCCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MRTXRTNMMVWDLI-UCQKPKSFSA-N 0.000 description 1
- PTXJDYVVRIWBRL-YVLHZVERSA-N CCOC(=O)C1=C(NC2=C(C)C=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PTXJDYVVRIWBRL-YVLHZVERSA-N 0.000 description 1
- FLFUSZPZSMOOMJ-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(N(C)CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(N(C)CCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FLFUSZPZSMOOMJ-MOSHPQCFSA-N 0.000 description 1
- ZCZDJQMOIQSXQN-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=C(C)C=C(NCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(NCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZCZDJQMOIQSXQN-UNOMPAQXSA-N 0.000 description 1
- MJFWBGQAHYUTSS-YVLHZVERSA-N CCOC(=O)C1=C(NC2=C(C)C=C(O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MJFWBGQAHYUTSS-YVLHZVERSA-N 0.000 description 1
- FUARRVBCBYKCIA-NDENLUEZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCC(C)(C)O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCC(C)(C)O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FUARRVBCBYKCIA-NDENLUEZSA-N 0.000 description 1
- YXUIWKJEAKYYCN-JMIUGGIZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCC(O)CO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCC(O)CO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YXUIWKJEAKYYCN-JMIUGGIZSA-N 0.000 description 1
- ZQLRKMQZGFRYBK-UCQKPKSFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=CC=NC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=CC=NC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZQLRKMQZGFRYBK-UCQKPKSFSA-N 0.000 description 1
- DHFQSDYDROYOAS-QRVIBDJDSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=CN=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=CN=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DHFQSDYDROYOAS-QRVIBDJDSA-N 0.000 description 1
- SVNKUJXSMLAPNB-UCQKPKSFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=NC=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCC3=NC=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O SVNKUJXSMLAPNB-UCQKPKSFSA-N 0.000 description 1
- IXUHJJOTCNYTSF-JLPGSUDCSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCC3=CC=CC=N3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCC3=CC=CC=N3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IXUHJJOTCNYTSF-JLPGSUDCSA-N 0.000 description 1
- DNWPWINHGPOBEA-UXTSPRGOSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCN(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO DNWPWINHGPOBEA-UXTSPRGOSA-N 0.000 description 1
- IDVCPWSSMYLKMB-KQWNVCNZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3C=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3C=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IDVCPWSSMYLKMB-KQWNVCNZSA-N 0.000 description 1
- LLEZBRGVMLLJPS-KQWNVCNZSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCN3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LLEZBRGVMLLJPS-KQWNVCNZSA-N 0.000 description 1
- JZJQKWVEYCTBTI-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JZJQKWVEYCTBTI-UNOMPAQXSA-N 0.000 description 1
- UTEFUOSDYQEOKA-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCOC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCOC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UTEFUOSDYQEOKA-MOSHPQCFSA-N 0.000 description 1
- MQQZWKGEFCFBBX-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCS(C)(=O)=O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCS(C)(=O)=O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MQQZWKGEFCFBBX-MOSHPQCFSA-N 0.000 description 1
- WBTGCMMZVNEXLR-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=C(C)C=C(OCCSC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=C(OCCSC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O WBTGCMMZVNEXLR-MOSHPQCFSA-N 0.000 description 1
- KENLUACKRNMYPI-SXGWCWSVSA-N CCOC(=O)C1=C(NC2=C(C)C=NC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)C=NC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O KENLUACKRNMYPI-SXGWCWSVSA-N 0.000 description 1
- XWQHSCRSZMPWFD-YVLHZVERSA-N CCOC(=O)C1=C(NC2=C(C)N=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(C)N=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XWQHSCRSZMPWFD-YVLHZVERSA-N 0.000 description 1
- FSQFLRKMUDLKJL-GXDHUFHOSA-N CCOC(=O)C1=C(NC2=C(F)C=C(OCCO)C=C2)C/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(F)C=C(OCCO)C=C2)C/C(=C\C2=CNC3=C2C=CC=N3)C1=O FSQFLRKMUDLKJL-GXDHUFHOSA-N 0.000 description 1
- AJAKPJCLCWVBFB-ODLFYWEKSA-N CCOC(=O)C1=C(NC2=C(F)C=C(OCCOC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(F)C=C(OCCOC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AJAKPJCLCWVBFB-ODLFYWEKSA-N 0.000 description 1
- NYAAABTZBKZPEI-YVLHZVERSA-N CCOC(=O)C1=C(NC2=C(O)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(O)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NYAAABTZBKZPEI-YVLHZVERSA-N 0.000 description 1
- COXQEYRZLVIIBA-ZDLGFXPLSA-N CCOC(=O)C1=C(NC2=C(OC)C=C(OC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(OC)C=C(OC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O COXQEYRZLVIIBA-ZDLGFXPLSA-N 0.000 description 1
- MOVWZUYSFZLTQN-STZFKDTASA-N CCOC(=O)C1=C(NC2=C(OCCN(C)C)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(OCCN(C)C)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MOVWZUYSFZLTQN-STZFKDTASA-N 0.000 description 1
- TXENGMPXDYPSBP-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=C(OCCO)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=C(OCCO)C=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O TXENGMPXDYPSBP-UNOMPAQXSA-N 0.000 description 1
- OEFGWKNCYYKGNP-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=C(Br)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(Br)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O OEFGWKNCYYKGNP-YBEGLDIGSA-N 0.000 description 1
- NTYNFKXPMJXZED-UNOMPAQXSA-N CCOC(=O)C1=C(NC2=CC=C(C(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(C(C)C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NTYNFKXPMJXZED-UNOMPAQXSA-N 0.000 description 1
- VRLQEIKXOBGZMX-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=C(C(N)=O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(C(N)=O)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VRLQEIKXOBGZMX-YBEGLDIGSA-N 0.000 description 1
- PPLFTIGHDVRREK-BOPFTXTBSA-N CCOC(=O)C1=C(NC2=CC=C(C)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(C)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O PPLFTIGHDVRREK-BOPFTXTBSA-N 0.000 description 1
- OOECXNOGEWTBKX-JCMHNJIXSA-N CCOC(=O)C1=C(NC2=CC=C(C3=CC=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(C3=CC=CC=C3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O OOECXNOGEWTBKX-JCMHNJIXSA-N 0.000 description 1
- MLHUNANKDNMWQY-YVLHZVERSA-N CCOC(=O)C1=C(NC2=CC=C(CO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(CO)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MLHUNANKDNMWQY-YVLHZVERSA-N 0.000 description 1
- IIFIDQKGJZMMCY-PXNMLYILSA-N CCOC(=O)C1=C(NC2=CC=C(F)C(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(F)C(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IIFIDQKGJZMMCY-PXNMLYILSA-N 0.000 description 1
- RJSWGRJJBNPMLC-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=C(N)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NC2=CC=C(N)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.Cl RJSWGRJJBNPMLC-YBEGLDIGSA-N 0.000 description 1
- KYRQUZPOCMNPQL-ZHZULCJRSA-N CCOC(=O)C1=C(NC2=CC=C(N3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(N3CCOCC3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O KYRQUZPOCMNPQL-ZHZULCJRSA-N 0.000 description 1
- WSLJGCJLTMKSCJ-ZDLGFXPLSA-N CCOC(=O)C1=C(NC2=CC=C(OC)C(OC)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(OC)C(OC)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O WSLJGCJLTMKSCJ-ZDLGFXPLSA-N 0.000 description 1
- HTNATCOWVLHAJO-BOPFTXTBSA-N CCOC(=O)C1=C(NC2=CC=C(OC)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(OC)C=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O HTNATCOWVLHAJO-BOPFTXTBSA-N 0.000 description 1
- WSVJXVWXBMBYHP-MOSHPQCFSA-N CCOC(=O)C1=C(NC2=CC=C(OCC3=NC=CC=N3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C(OCC3=NC=CC=N3)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O WSVJXVWXBMBYHP-MOSHPQCFSA-N 0.000 description 1
- GXYKMZXYSUDHTG-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=C([N+](=O)[O-])C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C([N+](=O)[O-])C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GXYKMZXYSUDHTG-YBEGLDIGSA-N 0.000 description 1
- IWRJUVPKPFCGNA-NVMNQCDNSA-N CCOC(=O)C1=C(NC2=CC=C3C=NCC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C3C=NCC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IWRJUVPKPFCGNA-NVMNQCDNSA-N 0.000 description 1
- MQQCFVHPLYYBGW-IUXPMGMMSA-N CCOC(=O)C1=C(NC2=CC=C3NC=NC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C3NC=NC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MQQCFVHPLYYBGW-IUXPMGMMSA-N 0.000 description 1
- QRLRBRNKSAOPJT-MFOYZWKCSA-N CCOC(=O)C1=C(NC2=CC=C3NN=CC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=C3NN=CC3=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QRLRBRNKSAOPJT-MFOYZWKCSA-N 0.000 description 1
- AUTKLRGSEUPLDF-YVLHZVERSA-N CCOC(=O)C1=C(NC2=CC=CC(OC)=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC(OC)=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O AUTKLRGSEUPLDF-YVLHZVERSA-N 0.000 description 1
- KGMJZRVANPEFFP-WJDWOHSUSA-N CCOC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O KGMJZRVANPEFFP-WJDWOHSUSA-N 0.000 description 1
- UXHVHQZCEWWVGN-BOPFTXTBSA-N CCOC(=O)C1=C(NC2=CC=CC=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UXHVHQZCEWWVGN-BOPFTXTBSA-N 0.000 description 1
- NDOCYYAXCZROFE-YBEGLDIGSA-N CCOC(=O)C1=C(NC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NDOCYYAXCZROFE-YBEGLDIGSA-N 0.000 description 1
- MKDIMMYNDUYZCP-BOPFTXTBSA-N CCOC(=O)C1=C(NC2=CC=CC=C2OC)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2OC)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O MKDIMMYNDUYZCP-BOPFTXTBSA-N 0.000 description 1
- QWGPRJZTEZEMID-ZHZULCJRSA-N CCOC(=O)C1=C(NC2=CC=CC=C2OCCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2OCCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QWGPRJZTEZEMID-ZHZULCJRSA-N 0.000 description 1
- NMKSKFRHQGNUFW-JWGURIENSA-N CCOC(=O)C1=C(NC2=CC=CC=C2OCCN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2OCCN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O NMKSKFRHQGNUFW-JWGURIENSA-N 0.000 description 1
- HIMOZMQRJXFYSX-PDGQHHTCSA-N CCOC(=O)C1=C(NC2=CC=CC=C2OCCO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=CC=C2OCCO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HIMOZMQRJXFYSX-PDGQHHTCSA-N 0.000 description 1
- LKHDWZQUXGBKIF-ZSOIEALJSA-N CCOC(=O)C1=C(NC2=CC=NC(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=NC(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LKHDWZQUXGBKIF-ZSOIEALJSA-N 0.000 description 1
- CUNBLKGSVPNPST-GDNBJRDFSA-N CCOC(=O)C1=C(NC2=CC=NC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CC=NC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CUNBLKGSVPNPST-GDNBJRDFSA-N 0.000 description 1
- OXHYUJUXDHLCDY-SXGWCWSVSA-N CCOC(=O)C1=C(NC2=CN=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CN=C(C)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O OXHYUJUXDHLCDY-SXGWCWSVSA-N 0.000 description 1
- LIFCKTCDAPUCMB-DHDCSXOGSA-N CCOC(=O)C1=C(NC2=CN=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CN=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LIFCKTCDAPUCMB-DHDCSXOGSA-N 0.000 description 1
- SRGMIHFPDVZTDS-NSIKDUERSA-N CCOC(=O)C1=C(NC2=CN=CN=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=CN=CN=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O SRGMIHFPDVZTDS-NSIKDUERSA-N 0.000 description 1
- JQVYTELIKNSPTP-UVTDQMKNSA-N CCOC(=O)C1=C(NC2=NC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=NC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O JQVYTELIKNSPTP-UVTDQMKNSA-N 0.000 description 1
- AWNHCJVNEYHOIZ-WQLSENKSSA-N CCOC(=O)C1=C(NC2=NNC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2=NNC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AWNHCJVNEYHOIZ-WQLSENKSSA-N 0.000 description 1
- JMXFTUQIOFNKPC-ODLFYWEKSA-N CCOC(=O)C1=C(NC2C3CC4CC(C3)CC2C4)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2C3CC4CC(C3)CC2C4)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JMXFTUQIOFNKPC-ODLFYWEKSA-N 0.000 description 1
- PBKVOMXAISHYCT-JYRVWZFOSA-N CCOC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PBKVOMXAISHYCT-JYRVWZFOSA-N 0.000 description 1
- IAEVEJFIEJPGKG-GDNBJRDFSA-N CCOC(=O)C1=C(NC2CCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2CCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IAEVEJFIEJPGKG-GDNBJRDFSA-N 0.000 description 1
- PEIOQHPQGXOJNE-WJDWOHSUSA-N CCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl PEIOQHPQGXOJNE-WJDWOHSUSA-N 0.000 description 1
- CBIGMLANHIBKPE-GDNBJRDFSA-N CCOC(=O)C1=C(NC2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NC2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CBIGMLANHIBKPE-GDNBJRDFSA-N 0.000 description 1
- RMSKWPXKMFBSSJ-WQLSENKSSA-N CCOC(=O)C1=C(NCC#N)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC#N)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RMSKWPXKMFBSSJ-WQLSENKSSA-N 0.000 description 1
- QKJSDIUUURAZLC-WQRHYEAKSA-N CCOC(=O)C1=C(NCC(=O)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC(=O)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QKJSDIUUURAZLC-WQRHYEAKSA-N 0.000 description 1
- HPWWXQPFGCCIIG-QPEQYQDCSA-N CCOC(=O)C1=C(NCC(C)O)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC(C)O)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HPWWXQPFGCCIIG-QPEQYQDCSA-N 0.000 description 1
- HLLPIWAOOUISSO-MLPAPPSSSA-N CCOC(=O)C1=C(NCC(O)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC(O)CO)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HLLPIWAOOUISSO-MLPAPPSSSA-N 0.000 description 1
- MYBZUJLRNDHEGX-DHDCSXOGSA-N CCOC(=O)C1=C(NCC2=C(C)C=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2=C(C)C=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MYBZUJLRNDHEGX-DHDCSXOGSA-N 0.000 description 1
- YTGRESPMFURJQM-YVLHZVERSA-N CCOC(=O)C1=C(NCC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YTGRESPMFURJQM-YVLHZVERSA-N 0.000 description 1
- UOKNXSKJWVJWCH-YVLHZVERSA-N CCOC(=O)C1=C(NCC2=CC=CC(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2=CC=CC(F)=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UOKNXSKJWVJWCH-YVLHZVERSA-N 0.000 description 1
- BIBSWGHUYKLAFI-BOPFTXTBSA-N CCOC(=O)C1=C(NCC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NCC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl BIBSWGHUYKLAFI-BOPFTXTBSA-N 0.000 description 1
- SPCGDHPJNPVBRM-YVLHZVERSA-N CCOC(=O)C1=C(NCC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O SPCGDHPJNPVBRM-YVLHZVERSA-N 0.000 description 1
- TVRNOBZYDVSYSM-DHDCSXOGSA-N CCOC(=O)C1=C(NCC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2=CC=CS2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O TVRNOBZYDVSYSM-DHDCSXOGSA-N 0.000 description 1
- LBQVSTFEDLERAV-ZSOIEALJSA-N CCOC(=O)C1=C(NCC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LBQVSTFEDLERAV-ZSOIEALJSA-N 0.000 description 1
- LBQFWODCSAOWHK-BOPFTXTBSA-N CCOC(=O)C1=C(NCC2CCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O Chemical compound CCOC(=O)C1=C(NCC2CCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O LBQFWODCSAOWHK-BOPFTXTBSA-N 0.000 description 1
- VTIGFWFJWFXHMO-NVNXTCNLSA-N CCOC(=O)C1=C(NCC2COC(C)(C)O2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCC2COC(C)(C)O2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VTIGFWFJWFXHMO-NVNXTCNLSA-N 0.000 description 1
- BGALXXFSGNRSEW-AQTBWJFISA-N CCOC(=O)C1=C(NCCC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl Chemical compound CCOC(=O)C1=C(NCCC2=CC=CC=C2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O.Cl BGALXXFSGNRSEW-AQTBWJFISA-N 0.000 description 1
- FQQOQWUUMVOMEV-UVTDQMKNSA-N CCOC(=O)C1=C(NCCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCCN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FQQOQWUUMVOMEV-UVTDQMKNSA-N 0.000 description 1
- FUTACAOOACKJSM-LCYFTJDESA-N CCOC(=O)C1=C(NCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NCCOC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FUTACAOOACKJSM-LCYFTJDESA-N 0.000 description 1
- GYVTUWIXUBJYGO-ATVHPVEESA-N CCOC(=O)C1=C(NN(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN(C)C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O GYVTUWIXUBJYGO-ATVHPVEESA-N 0.000 description 1
- CSRCZBNWEBPCQZ-LCYFTJDESA-N CCOC(=O)C1=C(NN(C)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN(C)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CSRCZBNWEBPCQZ-LCYFTJDESA-N 0.000 description 1
- JWFQSAMRLJWAGE-UVTDQMKNSA-N CCOC(=O)C1=C(NN(CC)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN(CC)CC)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JWFQSAMRLJWAGE-UVTDQMKNSA-N 0.000 description 1
- FVRUZTFHPIWUQP-ATVHPVEESA-N CCOC(=O)C1=C(NN2=CC=C(CC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2=CC=C(CC)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O FVRUZTFHPIWUQP-ATVHPVEESA-N 0.000 description 1
- ZLMVZKNYJWMGEG-BOPFTXTBSA-N CCOC(=O)C1=C(NN2C(C)CCCC2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2C(C)CCCC2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZLMVZKNYJWMGEG-BOPFTXTBSA-N 0.000 description 1
- WLCZEXCAEZLXPP-SDQBBNPISA-N CCOC(=O)C1=C(NN2C=NN=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2C=NN=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O WLCZEXCAEZLXPP-SDQBBNPISA-N 0.000 description 1
- ZDDAWQKQRHMMGY-GDNBJRDFSA-N CCOC(=O)C1=C(NN2CCC(O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCC(O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZDDAWQKQRHMMGY-GDNBJRDFSA-N 0.000 description 1
- IOGXNLLRYKBWMV-DHDCSXOGSA-N CCOC(=O)C1=C(NN2CCCC(O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCCC(O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IOGXNLLRYKBWMV-DHDCSXOGSA-N 0.000 description 1
- ZIXPJKZBUMZMKT-UVTDQMKNSA-N CCOC(=O)C1=C(NN2CCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ZIXPJKZBUMZMKT-UVTDQMKNSA-N 0.000 description 1
- QCQLZOGPJVGEMJ-PTNGSMBKSA-N CCOC(=O)C1=C(NN2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O QCQLZOGPJVGEMJ-PTNGSMBKSA-N 0.000 description 1
- JXULPDNEADLFBR-VBKFSLOCSA-N CCOC(=O)C1=C(NN2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JXULPDNEADLFBR-VBKFSLOCSA-N 0.000 description 1
- VDSUNFUHJNPOCC-WJDWOHSUSA-N CCOC(=O)C1=C(NN2CCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCN(C(C)=O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VDSUNFUHJNPOCC-WJDWOHSUSA-N 0.000 description 1
- MJHOWPILRYPKJW-PTNGSMBKSA-N CCOC(=O)C1=C(NN2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCN(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MJHOWPILRYPKJW-PTNGSMBKSA-N 0.000 description 1
- AWTJFSQBIJZIIZ-WJDWOHSUSA-N CCOC(=O)C1=C(NN2CCN(CC(C)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCN(CC(C)(F)F)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AWTJFSQBIJZIIZ-WJDWOHSUSA-N 0.000 description 1
- MUEGMPYHIZJVQY-JYRVWZFOSA-N CCOC(=O)C1=C(NN2CCNC(=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(NN2CCNC(=O)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MUEGMPYHIZJVQY-JYRVWZFOSA-N 0.000 description 1
- PKOUTPZZOVPLIE-BKMDOPFGSA-N CCOC(=O)C1=C(N[C@@H]2C[C@H]2C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N[C@@H]2C[C@H]2C2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O PKOUTPZZOVPLIE-BKMDOPFGSA-N 0.000 description 1
- XUYBCVIWMGTAFB-CCYAHBIWSA-N CCOC(=O)C1=C(N[C@H]2CC[C@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CCOC(=O)C1=C(N[C@H]2CC[C@H](O)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O XUYBCVIWMGTAFB-CCYAHBIWSA-N 0.000 description 1
- YUVNUXDEMUKFFG-STZFKDTASA-N CCOC(C(C1=O)=C(Nc(c(C)c2)ccc2OCCN(C)C)O/C1=C\c1c[nH]c2c1cccn2)=O Chemical compound CCOC(C(C1=O)=C(Nc(c(C)c2)ccc2OCCN(C)C)O/C1=C\c1c[nH]c2c1cccn2)=O YUVNUXDEMUKFFG-STZFKDTASA-N 0.000 description 1
- USSYEYUNJDPSBW-YYTPVVGHSA-N CC[C@@H](C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC[C@@H](C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O USSYEYUNJDPSBW-YYTPVVGHSA-N 0.000 description 1
- USSYEYUNJDPSBW-RERGGYADSA-N CC[C@H](C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CC[C@H](C)OC(=O)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O USSYEYUNJDPSBW-RERGGYADSA-N 0.000 description 1
- CPYWMEVSEOPQGU-JHMJKTBASA-N CN(C)C(C)(C)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CN(C)C(C)(C)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO CPYWMEVSEOPQGU-JHMJKTBASA-N 0.000 description 1
- SKUCIUTYINMHHM-NYAKATHWSA-N CN(C)CCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CN(C)CCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO SKUCIUTYINMHHM-NYAKATHWSA-N 0.000 description 1
- WUOGMKOVWLTYKX-UWRQUICRSA-N CN(C)CCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CN(C)CCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO WUOGMKOVWLTYKX-UWRQUICRSA-N 0.000 description 1
- LSDRNABVGGUUAQ-AQTBWJFISA-N CN(C)CCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound CN(C)CCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LSDRNABVGGUUAQ-AQTBWJFISA-N 0.000 description 1
- LVHBTLUNIVKQDX-LCYFTJDESA-N CN(C)NC1=C(C(=O)OCCCO)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound CN(C)NC1=C(C(=O)OCCCO)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 LVHBTLUNIVKQDX-LCYFTJDESA-N 0.000 description 1
- JQNHNPVOLVBKPT-YBEGLDIGSA-N CN(CC1=CC=CS1)C1=C(C(=O)OCCO)C(=O)/C(=C/C2=CNC3=NC=CC=C23)O1 Chemical compound CN(CC1=CC=CS1)C1=C(C(=O)OCCO)C(=O)/C(=C/C2=CNC3=NC=CC=C23)O1 JQNHNPVOLVBKPT-YBEGLDIGSA-N 0.000 description 1
- MMMRYWDLPOYNPG-GNWMQEPYSA-N CN1CCC(COC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO Chemical compound CN1CCC(COC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO MMMRYWDLPOYNPG-GNWMQEPYSA-N 0.000 description 1
- CBHFYQORNDQETQ-BKUYFWCQSA-N CN1CCC(COC(C(C2=O)=C(Nc(cc3)ccc3F)O/C2=C\c2c[nH]c3ncccc23)=O)CC1 Chemical compound CN1CCC(COC(C(C2=O)=C(Nc(cc3)ccc3F)O/C2=C\c2c[nH]c3ncccc23)=O)CC1 CBHFYQORNDQETQ-BKUYFWCQSA-N 0.000 description 1
- YBPGDIPHNUGURW-SXGWCWSVSA-N CN1CCC(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 Chemical compound CN1CCC(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)CC1 YBPGDIPHNUGURW-SXGWCWSVSA-N 0.000 description 1
- XNZOOVISESBQKY-MASIZSFYSA-N CN1CCC(OC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO Chemical compound CN1CCC(OC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO XNZOOVISESBQKY-MASIZSFYSA-N 0.000 description 1
- ULQMKDGXIFPFQV-GNWMQEPYSA-N CN1CCCCC1COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound CN1CCCCC1COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO ULQMKDGXIFPFQV-GNWMQEPYSA-N 0.000 description 1
- NTFDWCUVJUIIBD-XGRJIHFXSA-N CN1CCN(CCOC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO Chemical compound CN1CCN(CCOC(=O)C2=C(NC3=CC=C(F)C=C3)O/C(=C\C3=CNC4=C3C=CC=N4)C2=O)CC1.O=CO NTFDWCUVJUIIBD-XGRJIHFXSA-N 0.000 description 1
- HIMUMXYXUVFIAW-QNGOZBTKSA-N CN1CCN(CCOC(C(C2=O)=C(Nc(cc3)ccc3F)O/C2=C\c2c[nH]c3c2cccn3)=O)CC1 Chemical compound CN1CCN(CCOC(C(C2=O)=C(Nc(cc3)ccc3F)O/C2=C\c2c[nH]c3c2cccn3)=O)CC1 HIMUMXYXUVFIAW-QNGOZBTKSA-N 0.000 description 1
- BYMAWRFWNZGBIP-CHHVJCJISA-N COC(=O)C1=C(NC2=C(F)C=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NC2=C(F)C=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BYMAWRFWNZGBIP-CHHVJCJISA-N 0.000 description 1
- AZGFLBZQLRLLBM-GDNBJRDFSA-N COC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NC2=CC=CC=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AZGFLBZQLRLLBM-GDNBJRDFSA-N 0.000 description 1
- MVXOVAYQEQXSDU-GHXNOFRVSA-N COC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MVXOVAYQEQXSDU-GHXNOFRVSA-N 0.000 description 1
- LSDOHHYPDJXLOE-SXGWCWSVSA-N COC(=O)C1=C(NCC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NCC2=CC=CC=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LSDOHHYPDJXLOE-SXGWCWSVSA-N 0.000 description 1
- IBRPAWDRAZDXHP-QPEQYQDCSA-N COC(=O)C1=C(NCC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COC(=O)C1=C(NCC2CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IBRPAWDRAZDXHP-QPEQYQDCSA-N 0.000 description 1
- ZJETYVKMHDIFEH-IUXPMGMMSA-N COC1=C(OC)C=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound COC1=C(OC)C=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 ZJETYVKMHDIFEH-IUXPMGMMSA-N 0.000 description 1
- JRFALVIUIDOJPN-LSCVHKIXSA-N COC1=CC(OC)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound COC1=CC(OC)=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 JRFALVIUIDOJPN-LSCVHKIXSA-N 0.000 description 1
- OFLIKQBYLKTOMO-MTJSOVHGSA-N COC1=CC2=C(C=C1)CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 Chemical compound COC1=CC2=C(C=C1)CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 OFLIKQBYLKTOMO-MTJSOVHGSA-N 0.000 description 1
- MQUCEZIEMCWLIJ-MTJSOVHGSA-N COC1=CC2=C(C=C1)CN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)CC2 Chemical compound COC1=CC2=C(C=C1)CN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)CC2 MQUCEZIEMCWLIJ-MTJSOVHGSA-N 0.000 description 1
- WUDMCCMTZLAUMA-MFOYZWKCSA-N COC1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound COC1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 WUDMCCMTZLAUMA-MFOYZWKCSA-N 0.000 description 1
- QONONOPLIRJLMR-MTJSOVHGSA-N COC1=CC=CC2=C1CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 Chemical compound COC1=CC=CC2=C1CCN(C1=C(C(=O)OC(C)C)C(=O)/C(=C/C3=CNC4=C3C=CC=N4)O1)C2 QONONOPLIRJLMR-MTJSOVHGSA-N 0.000 description 1
- CRCSGMWMCJGAEY-MFOYZWKCSA-N COC1=CC=CC=C1NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound COC1=CC=CC=C1NC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 CRCSGMWMCJGAEY-MFOYZWKCSA-N 0.000 description 1
- QZFIEHPUMIKWOG-GRSHGNNSSA-N COCC(=O)C1=C(CC2=CC=CC=C2O)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound COCC(=O)C1=C(CC2=CC=CC=C2O)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O QZFIEHPUMIKWOG-GRSHGNNSSA-N 0.000 description 1
- FYIVOOLTHVWOHP-WQLSENKSSA-N COCCNC1=C(C(=O)OC)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound COCCNC1=C(C(=O)OC)C(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 FYIVOOLTHVWOHP-WQLSENKSSA-N 0.000 description 1
- VKFIBKFNDCKJFL-QPEQYQDCSA-N COCCNC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 Chemical compound COCCNC1=CC(=O)/C(=C/C2=CNC3=C2C=CC=N3)O1 VKFIBKFNDCKJFL-QPEQYQDCSA-N 0.000 description 1
- NPTDGZSLLHZCBJ-BOPFTXTBSA-N COCCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O Chemical compound COCCOC(=O)C1=C(N(C)CC2=CC=CS2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O NPTDGZSLLHZCBJ-BOPFTXTBSA-N 0.000 description 1
- AOLFXUGUZKSEOC-ATVHPVEESA-N COCCOC(=O)C1=C(N2CCC(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(N2CCC(C)CC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AOLFXUGUZKSEOC-ATVHPVEESA-N 0.000 description 1
- IQBTVBSMABYUGK-MOSHPQCFSA-N COCCOC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IQBTVBSMABYUGK-MOSHPQCFSA-N 0.000 description 1
- HZNPECADQYLKMC-LGMDPLHJSA-N COCCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2/C=C\C=N/3)C1=O Chemical compound COCCOC(=O)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2/C=C\C=N/3)C1=O HZNPECADQYLKMC-LGMDPLHJSA-N 0.000 description 1
- JNPJTJUWUIOSQR-BKUYFWCQSA-N COCCOC(=O)C1=C(NC2=CC=C(CN(C)C)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2=CC=C(CN(C)C)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JNPJTJUWUIOSQR-BKUYFWCQSA-N 0.000 description 1
- UMCJTLYFEJYPQN-BOPFTXTBSA-N COCCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O UMCJTLYFEJYPQN-BOPFTXTBSA-N 0.000 description 1
- HBWHCZBKSGOLMV-MOSHPQCFSA-N COCCOC(=O)C1=C(NC2=CC=C(NCCO)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2=CC=C(NCCO)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HBWHCZBKSGOLMV-MOSHPQCFSA-N 0.000 description 1
- AQMBSYLOOCMGRU-ULJHMMPZSA-N COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCOCC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2=CC=C(OCCN3CCOCC3)C=C2C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O AQMBSYLOOCMGRU-ULJHMMPZSA-N 0.000 description 1
- HHVAAELVAVJBPM-BOPFTXTBSA-N COCCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HHVAAELVAVJBPM-BOPFTXTBSA-N 0.000 description 1
- DHLQFLPZSQTILQ-ATVHPVEESA-N COCCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NC2CCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DHLQFLPZSQTILQ-ATVHPVEESA-N 0.000 description 1
- CHVRSDUOGFCSIZ-LCYFTJDESA-N COCCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound COCCOC(=O)C1=C(NN(C)C)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CHVRSDUOGFCSIZ-LCYFTJDESA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- HBKSBNDLWGLFHJ-UHFFFAOYSA-N Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(N)C=C1 Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(N)C=C1 HBKSBNDLWGLFHJ-UHFFFAOYSA-N 0.000 description 1
- PZLGFQJLORYDKY-UHFFFAOYSA-N Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCO)=C1C1=CC=CC=CN1 Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCO)=C1C1=CC=CC=CN1 PZLGFQJLORYDKY-UHFFFAOYSA-N 0.000 description 1
- HANLGXCTSPJBFM-VBKFSLOCSA-N Cl.O=C(OCCO)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O Chemical compound Cl.O=C(OCCO)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=NC=CC=C23)C1=O HANLGXCTSPJBFM-VBKFSLOCSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000975821 Homo sapiens Arylsulfatase K Proteins 0.000 description 1
- 101000721172 Homo sapiens Protein DBF4 homolog A Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- XRRGNLMVTNOFEA-PXNMLYILSA-N NC(=O)C1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 Chemical compound NC(=O)C1=CC=C(NC2=CC(=O)/C(=C/C3=CNC4=C3C=CC=N4)O2)C=C1 XRRGNLMVTNOFEA-PXNMLYILSA-N 0.000 description 1
- IZUUOHBYLNGVGA-NVNXTCNLSA-N NC(=O)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound NC(=O)COC(=O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IZUUOHBYLNGVGA-NVNXTCNLSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VIIFLQJEKHVDMB-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NN1CCN(CC(F)(F)F)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NN1CCN(CC(F)(F)F)CC1 VIIFLQJEKHVDMB-UHFFFAOYSA-N 0.000 description 1
- KAWQVABMGGJMAI-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1C1=CC=CC=CN1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1C1=CC=CC=CN1 KAWQVABMGGJMAI-UHFFFAOYSA-N 0.000 description 1
- FHTDIJZGIBFLLX-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(N(C)CCN(C)C)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(N(C)CCN(C)C)CC1 FHTDIJZGIBFLLX-UHFFFAOYSA-N 0.000 description 1
- NDQIDZYOKPEFKN-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(C)(C)C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(C)(C)C1 NDQIDZYOKPEFKN-UHFFFAOYSA-N 0.000 description 1
- ODPUNLAWIUSDRN-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(CO)C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(CO)C1 ODPUNLAWIUSDRN-UHFFFAOYSA-N 0.000 description 1
- FEPRRKQKIZUSKK-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCNCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCNCC1 FEPRRKQKIZUSKK-UHFFFAOYSA-N 0.000 description 1
- QULDPGALDVOIHD-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCN(CC(F)(F)F)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCN(CC(F)(F)F)CC1 QULDPGALDVOIHD-UHFFFAOYSA-N 0.000 description 1
- YCZPJAOVFOJXLU-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCSCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCSCC1 YCZPJAOVFOJXLU-UHFFFAOYSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-OKILXGFUSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@@H](C)C[C@@H](C)C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@@H](C)C[C@@H](C)C1 YUYFSQWXJPLOEZ-OKILXGFUSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-KBPBESRZSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@@H](C)C[C@H](C)C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@@H](C)C[C@H](C)C1 YUYFSQWXJPLOEZ-KBPBESRZSA-N 0.000 description 1
- BDLOOGGKJOBMIB-BETUJISGSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@H](C)O[C@H](C)C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1C[C@H](C)O[C@H](C)C1 BDLOOGGKJOBMIB-BETUJISGSA-N 0.000 description 1
- IHGBHCIBLCKJDZ-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCC(O)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCC(O)CC1 IHGBHCIBLCKJDZ-UHFFFAOYSA-N 0.000 description 1
- BIBDMJYHPVEIMT-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCCC1 BIBDMJYHPVEIMT-UHFFFAOYSA-N 0.000 description 1
- AZDFVHOCZFBOCS-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCN(C)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CCN1CCN(C)CC1 AZDFVHOCZFBOCS-UHFFFAOYSA-N 0.000 description 1
- REYPFEXPHPGXNJ-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCN(C(C)C)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCN(C(C)C)CC1 REYPFEXPHPGXNJ-UHFFFAOYSA-N 0.000 description 1
- ZQLRKMQZGFRYBK-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=NC=C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=NC=C1 ZQLRKMQZGFRYBK-UHFFFAOYSA-N 0.000 description 1
- LLEZBRGVMLLJPS-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCN1CCOCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCN1CCOCC1 LLEZBRGVMLLJPS-UHFFFAOYSA-N 0.000 description 1
- NBUZPOPTANVLMD-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C#CCN(C)C)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C#CCN(C)C)C=C1C NBUZPOPTANVLMD-UHFFFAOYSA-N 0.000 description 1
- BNRXOZGYCGMTNM-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1C BNRXOZGYCGMTNM-UHFFFAOYSA-N 0.000 description 1
- HVSZNKCXHKZIKQ-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CC#N)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CC#N)C=C1C HVSZNKCXHKZIKQ-UHFFFAOYSA-N 0.000 description 1
- NTFGMTBQNVRERX-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CCN(C)C)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CCN(C)C)C=C1C NTFGMTBQNVRERX-UHFFFAOYSA-N 0.000 description 1
- HPZRJNZNFXISMN-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CNC)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CNC)C=C1C HPZRJNZNFXISMN-UHFFFAOYSA-N 0.000 description 1
- ZCZDJQMOIQSXQN-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(NCCO)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(NCCO)C=C1C ZCZDJQMOIQSXQN-UHFFFAOYSA-N 0.000 description 1
- RQXJZQPFALMNSB-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCCO)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCCO)C=C1C RQXJZQPFALMNSB-UHFFFAOYSA-N 0.000 description 1
- UTEFUOSDYQEOKA-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOC)C=C1C Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOC)C=C1C UTEFUOSDYQEOKA-UHFFFAOYSA-N 0.000 description 1
- GXYKMZXYSUDHTG-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C([N+]([O-])=O)C=C1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C([N+]([O-])=O)C=C1 GXYKMZXYSUDHTG-UHFFFAOYSA-N 0.000 description 1
- HIMOZMQRJXFYSX-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCO Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCO HIMOZMQRJXFYSX-UHFFFAOYSA-N 0.000 description 1
- KAYUXTPZGXZNDI-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCCCCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCCCCC1 KAYUXTPZGXZNDI-UHFFFAOYSA-N 0.000 description 1
- CBIGMLANHIBKPE-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCOCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCOCC1 CBIGMLANHIBKPE-UHFFFAOYSA-N 0.000 description 1
- VDSUNFUHJNPOCC-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCN(C(C)=O)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCN(C(C)=O)CC1 VDSUNFUHJNPOCC-UHFFFAOYSA-N 0.000 description 1
- XUYBCVIWMGTAFB-OKILXGFUSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N[C@@H]1CC[C@H](O)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N[C@@H]1CC[C@H](O)CC1 XUYBCVIWMGTAFB-OKILXGFUSA-N 0.000 description 1
- XUYBCVIWMGTAFB-HDJSIYSDSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N[C@H]1CC[C@H](O)CC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N[C@H]1CC[C@H](O)CC1 XUYBCVIWMGTAFB-HDJSIYSDSA-N 0.000 description 1
- NJPVLMURJIOCDA-UHFFFAOYSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCO)=C1C1=CC=CC=CN1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCO)=C1C1=CC=CC=CN1 NJPVLMURJIOCDA-UHFFFAOYSA-N 0.000 description 1
- USSYEYUNJDPSBW-ZDUSSCGKSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O[C@@H](C)CC)=C1NN1CCOCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O[C@@H](C)CC)=C1NN1CCOCC1 USSYEYUNJDPSBW-ZDUSSCGKSA-N 0.000 description 1
- USSYEYUNJDPSBW-CYBMUJFWSA-N O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O[C@H](C)CC)=C1NN1CCOCC1 Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)O[C@H](C)CC)=C1NN1CCOCC1 USSYEYUNJDPSBW-CYBMUJFWSA-N 0.000 description 1
- RBFXNIQIQJCOPG-MGCOHNPYSA-N O1CC(=O)C(C(=O)OC(C)C)=C1N[C@@H]1CC[C@@H](O)CC1 Chemical compound O1CC(=O)C(C(=O)OC(C)C)=C1N[C@@H]1CC[C@@H](O)CC1 RBFXNIQIQJCOPG-MGCOHNPYSA-N 0.000 description 1
- YPFNOHSKZMOEDY-KYZUINATSA-N O1CC(=O)C(C(=O)OCC)=C1N[C@@H]1CC[C@@H](O)CC1 Chemical compound O1CC(=O)C(C(=O)OCC)=C1N[C@@H]1CC[C@@H](O)CC1 YPFNOHSKZMOEDY-KYZUINATSA-N 0.000 description 1
- NVDXBUVYHYUBOQ-ZHZULCJRSA-N O=C(C(C1=O)=C(Nc(cc2)ccc2F)O/C1=C\c1c[nH]c2ncccc12)OCCN1CCCC1 Chemical compound O=C(C(C1=O)=C(Nc(cc2)ccc2F)O/C1=C\c1c[nH]c2ncccc12)OCCN1CCCC1 NVDXBUVYHYUBOQ-ZHZULCJRSA-N 0.000 description 1
- SASWFXQWNYXTJT-IDUWFGFVSA-N O=C(C=C(Nc(cc1)cc2c1[nH]nc2)O1)/C1=C/c1c[nH]c2c1cccn2 Chemical compound O=C(C=C(Nc(cc1)cc2c1[nH]nc2)O1)/C1=C/c1c[nH]c2c1cccn2 SASWFXQWNYXTJT-IDUWFGFVSA-N 0.000 description 1
- XSXLTIGVUOLSGZ-LCYFTJDESA-N O=C(O)C1=C(N2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O Chemical compound O=C(O)C1=C(N2CCCCC2)O/C(=C\C2=C\NC3=C2C=CC=N3)C1=O XSXLTIGVUOLSGZ-LCYFTJDESA-N 0.000 description 1
- BRMZTMVZRJVMQT-NSIKDUERSA-N O=C(O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(O)C1=C(NC2=CC=C(F)C=C2F)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O BRMZTMVZRJVMQT-NSIKDUERSA-N 0.000 description 1
- JJIJXLCWKOWIBQ-NDENLUEZSA-N O=C(OC1CCC(O)CC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OC1CCC(O)CC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O JJIJXLCWKOWIBQ-NDENLUEZSA-N 0.000 description 1
- IHYKEDLMMWGNKV-ATVHPVEESA-N O=C(OC1CCCC1)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OC1CCCC1)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O IHYKEDLMMWGNKV-ATVHPVEESA-N 0.000 description 1
- RBWXDMCMOZKIRO-ZDLGFXPLSA-N O=C(OCC1CC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCC1CC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O RBWXDMCMOZKIRO-ZDLGFXPLSA-N 0.000 description 1
- DFGUMJXSVMMIMF-MOSHPQCFSA-N O=C(OCCCO)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(N2CCC3=C(C=CC=C3)C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O DFGUMJXSVMMIMF-MOSHPQCFSA-N 0.000 description 1
- ARMNMNAUFUUQEA-LGMDPLHJSA-N O=C(OCCCO)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(N2CCCCCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O ARMNMNAUFUUQEA-LGMDPLHJSA-N 0.000 description 1
- LIRLKPYEZYIKOO-BOPFTXTBSA-N O=C(OCCCO)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O LIRLKPYEZYIKOO-BOPFTXTBSA-N 0.000 description 1
- VKUNEFVUDFDMNP-BOPFTXTBSA-N O=C(OCCCO)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VKUNEFVUDFDMNP-BOPFTXTBSA-N 0.000 description 1
- HCTQZHXPHAFUHF-PTNGSMBKSA-N O=C(OCCCO)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCCO)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O HCTQZHXPHAFUHF-PTNGSMBKSA-N 0.000 description 1
- CBYYONPYJYDFCF-VSOKSMTPSA-N O=C(OCCN1CCCC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound O=C(OCCN1CCCC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO CBYYONPYJYDFCF-VSOKSMTPSA-N 0.000 description 1
- YBJCGHJRNDWWTQ-VSOKSMTPSA-N O=C(OCCN1CCOCC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO Chemical compound O=C(OCCN1CCOCC1)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O.O=CO YBJCGHJRNDWWTQ-VSOKSMTPSA-N 0.000 description 1
- YSSHWLBCVUMRSF-YBEGLDIGSA-N O=C(OCCO)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCO)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O YSSHWLBCVUMRSF-YBEGLDIGSA-N 0.000 description 1
- CMNUAIRJJOJDEB-YBEGLDIGSA-N O=C(OCCO)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCO)C1=C(NC2=CC=CC=C2Cl)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O CMNUAIRJJOJDEB-YBEGLDIGSA-N 0.000 description 1
- VBZSXAIBCOTNSJ-UVTDQMKNSA-N O=C(OCCO)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(OCCO)C1=C(NN2CCOCC2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O VBZSXAIBCOTNSJ-UVTDQMKNSA-N 0.000 description 1
- MASJTUZPZLGVRK-BKMDOPFGSA-N O=C(O[C@@H]1CCC[C@@H]1O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O Chemical compound O=C(O[C@@H]1CCC[C@@H]1O)C1=C(NC2=CC=C(F)C=C2)O/C(=C\C2=CNC3=C2C=CC=N3)C1=O MASJTUZPZLGVRK-BKMDOPFGSA-N 0.000 description 1
- WVWXGSVOTIYYLF-PXNMLYILSA-N O=C1C=C(NC2=C(Cl)C=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=C(Cl)C=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 WVWXGSVOTIYYLF-PXNMLYILSA-N 0.000 description 1
- YWKSBXQXBKBELT-SOFYXZRVSA-N O=C1C=C(NC2=C(F)C=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=C(F)C=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 YWKSBXQXBKBELT-SOFYXZRVSA-N 0.000 description 1
- GYRXCWYLFGWBNW-APSNUPSMSA-N O=C1C=C(NC2=CC(Cl)=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC(Cl)=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 GYRXCWYLFGWBNW-APSNUPSMSA-N 0.000 description 1
- DCPBCPPKVBCGIT-GRSHGNNSSA-N O=C1C=C(NC2=CC3=C(C=C2)CC=C3)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC3=C(C=C2)CC=C3)O/C1=C\C1=CNC2=C1C=CC=N2 DCPBCPPKVBCGIT-GRSHGNNSSA-N 0.000 description 1
- WDLHXDBUZNLHEG-GRSHGNNSSA-N O=C1C=C(NC2=CC3=C(C=C2)N=CC=C3)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC3=C(C=C2)N=CC=C3)O/C1=C\C1=CNC2=C1C=CC=N2 WDLHXDBUZNLHEG-GRSHGNNSSA-N 0.000 description 1
- RLVRYKARNLJPEV-PXNMLYILSA-N O=C1C=C(NC2=CC=C(Br)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=C(Br)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 RLVRYKARNLJPEV-PXNMLYILSA-N 0.000 description 1
- ZMENMBCADVVOOH-XKZIYDEJSA-N O=C1C=C(NC2=CC=C(C3=CC=CC=C3)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=C(C3=CC=CC=C3)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 ZMENMBCADVVOOH-XKZIYDEJSA-N 0.000 description 1
- ZBEABLDVTBXNOM-PXNMLYILSA-N O=C1C=C(NC2=CC=C(Cl)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=C(Cl)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 ZBEABLDVTBXNOM-PXNMLYILSA-N 0.000 description 1
- IEPZNIMPOMDPEN-PXNMLYILSA-N O=C1C=C(NC2=CC=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 IEPZNIMPOMDPEN-PXNMLYILSA-N 0.000 description 1
- HSLBRNLNLFIWCY-ZDLGFXPLSA-N O=C1C=C(NC2=CC=CC=C2OCCO)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CC=CC=C2OCCO)O/C1=C\C1=CNC2=C1C=CC=N2 HSLBRNLNLFIWCY-ZDLGFXPLSA-N 0.000 description 1
- AWQHDLBFBQMHPS-CHHVJCJISA-N O=C1C=C(NC2=CN=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=CN=CC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 AWQHDLBFBQMHPS-CHHVJCJISA-N 0.000 description 1
- UYTPBUYLVLFICC-SDQBBNPISA-N O=C1C=C(NC2=NNC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2=NNC=C2)O/C1=C\C1=CNC2=C1C=CC=N2 UYTPBUYLVLFICC-SDQBBNPISA-N 0.000 description 1
- QYWMVXVYGUKTID-OCKHKDLRSA-N O=C1C=C(NC2C3CC4CC(C3)CC2C4)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2C3CC4CC(C3)CC2C4)O/C1=C\C1=CNC2=C1C=CC=N2 QYWMVXVYGUKTID-OCKHKDLRSA-N 0.000 description 1
- ABUCORORNRDRIL-MLPAPPSSSA-N O=C1C=C(NC2CC2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2CC2)O/C1=C\C1=CNC2=C1C=CC=N2 ABUCORORNRDRIL-MLPAPPSSSA-N 0.000 description 1
- BXDGIQJPVZDRBS-NVNXTCNLSA-N O=C1C=C(NC2CCCC2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NC2CCCC2)O/C1=C\C1=CNC2=C1C=CC=N2 BXDGIQJPVZDRBS-NVNXTCNLSA-N 0.000 description 1
- PRDAOPGPHPDLMU-IUXPMGMMSA-N O=C1C=C(NCC2=CC=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NCC2=CC=C(F)C=C2)O/C1=C\C1=CNC2=C1C=CC=N2 PRDAOPGPHPDLMU-IUXPMGMMSA-N 0.000 description 1
- PDLMXTIGAHGYDL-IUXPMGMMSA-N O=C1C=C(NCC2=CC=CC(F)=C2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NCC2=CC=CC(F)=C2)O/C1=C\C1=CNC2=C1C=CC=N2 PDLMXTIGAHGYDL-IUXPMGMMSA-N 0.000 description 1
- BAPKTBYTNVHNKC-IUXPMGMMSA-N O=C1C=C(NCC2=CC=CC=C2F)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NCC2=CC=CC=C2F)O/C1=C\C1=CNC2=C1C=CC=N2 BAPKTBYTNVHNKC-IUXPMGMMSA-N 0.000 description 1
- XBXMWCYPNMZTLF-CHHVJCJISA-N O=C1C=C(NCC2=CC=CS2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(NCC2=CC=CS2)O/C1=C\C1=CNC2=C1C=CC=N2 XBXMWCYPNMZTLF-CHHVJCJISA-N 0.000 description 1
- CWBCVKHGWWNUSU-VOZKLQLBSA-N O=C1C=C(N[C@H]2CC[C@H](O)CC2)O/C1=C\C1=CNC2=C1C=CC=N2 Chemical compound O=C1C=C(N[C@H]2CC[C@H](O)CC2)O/C1=C\C1=CNC2=C1C=CC=N2 CWBCVKHGWWNUSU-VOZKLQLBSA-N 0.000 description 1
- TXGSBCRFQKFSEB-UHFFFAOYSA-N OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1C1=CC=CC=CN1 Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1C1=CC=CC=CN1 TXGSBCRFQKFSEB-UHFFFAOYSA-N 0.000 description 1
- TUWHMYMEEDKTOR-UHFFFAOYSA-N OC=O.OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1=CC=C(CN(C)C)C=C1C Chemical compound OC=O.OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1=CC=C(CN(C)C)C=C1C TUWHMYMEEDKTOR-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- MASJTUZPZLGVRK-ZWKOTPCHSA-N O[C@H]1CCC[C@H]1OC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 Chemical compound O[C@H]1CCC[C@H]1OC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 MASJTUZPZLGVRK-ZWKOTPCHSA-N 0.000 description 1
- XGEAUXVPBXUBKN-WUFINQPMSA-N Obamegine Chemical compound C([C@H]1N(C)CCC=2C=C(C(=C(OC3=C(OC)C=C4CCN(C)[C@H](C4=C3)CC3=CC=C(C=C3)O3)C=21)O)OC)C1=CC=C(O)C3=C1 XGEAUXVPBXUBKN-WUFINQPMSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 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
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- CPYWMEVSEOPQGU-UHFFFAOYSA-N [2-(dimethylamino)-2-methylpropyl] 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC(C)(C)N(C)C)=C1NC1=CC=C(F)C=C1 CPYWMEVSEOPQGU-UHFFFAOYSA-N 0.000 description 1
- CBOUSNFCAKXFEO-UHFFFAOYSA-N acetic acid;2-(dimethylamino)ethyl 2-(2,2-dimethylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O=C1C(C(=O)OCCN(C)C)=C(NN(C)C)OC1=CC1=CNC2=NC=CC=C12 CBOUSNFCAKXFEO-UHFFFAOYSA-N 0.000 description 1
- WHEPMJXNBKLMTM-UHFFFAOYSA-N acetic acid;2-(dimethylamino)ethyl 2-(2-chloroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NC1=CC=CC=C1Cl WHEPMJXNBKLMTM-UHFFFAOYSA-N 0.000 description 1
- LEFOJSGQLAMDPP-UHFFFAOYSA-N acetic acid;2-(dimethylamino)ethyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCN(C)C)=C1NN1CCOCC1 LEFOJSGQLAMDPP-UHFFFAOYSA-N 0.000 description 1
- SUAAFADPFXVOPM-UHFFFAOYSA-N acetic acid;2-methoxyethyl 2-[2-methyl-4-(2-pyrrolidin-1-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCOC)=C1NC(C(=C1)C)=CC=C1OCCN1CCCC1 SUAAFADPFXVOPM-UHFFFAOYSA-N 0.000 description 1
- BASONKLBMORCNE-UHFFFAOYSA-N acetic acid;ethyl 2-(4-methyl-1,4-diazepan-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCN(C)CC1 BASONKLBMORCNE-UHFFFAOYSA-N 0.000 description 1
- CWDZGIKSAOKXDJ-UHFFFAOYSA-N acetic acid;ethyl 2-[2-methyl-4-(2-pyrrolidin-1-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCN1CCCC1 CWDZGIKSAOKXDJ-UHFFFAOYSA-N 0.000 description 1
- LDVPSDQUACPLAV-UHFFFAOYSA-N acetic acid;ethyl 2-[2-methyl-4-(2-pyrrolidin-1-ylethylamino)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1NCCN1CCCC1 LDVPSDQUACPLAV-UHFFFAOYSA-N 0.000 description 1
- SKDQVPCAUGDPIU-UHFFFAOYSA-N acetic acid;ethyl 2-[2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCN1CCN(C)CC1 SKDQVPCAUGDPIU-UHFFFAOYSA-N 0.000 description 1
- ZSBSLECPMZDMCH-UHFFFAOYSA-N acetic acid;ethyl 2-[4-[2-(diethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC(O)=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCN(CC)CC)C=C1C ZSBSLECPMZDMCH-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- RFJXRHBBOAYUPB-UHFFFAOYSA-N butyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCC)=C1NC1=CC=C(F)C=C1 RFJXRHBBOAYUPB-UHFFFAOYSA-N 0.000 description 1
- CTDMIIHLYDCSHI-UHFFFAOYSA-N butyl 2-[4-(2-hydroxyethoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCC)=C1NC1=CC=C(OCCO)C=C1C CTDMIIHLYDCSHI-UHFFFAOYSA-N 0.000 description 1
- JBCFIQFWUOLNRR-UHFFFAOYSA-N butyl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCC)=C1NC1=CC=C(OCCN(C)C)C=C1C JBCFIQFWUOLNRR-UHFFFAOYSA-N 0.000 description 1
- ABEGWRABXMPHPY-UHFFFAOYSA-N butyl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCCC)=C1N(C)CC1=CC=CS1 ABEGWRABXMPHPY-UHFFFAOYSA-N 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cis-cyclohexene Natural products C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- RLMGYIOTPQVQJR-UHFFFAOYSA-N cyclohexane-1,3-diol Chemical compound OC1CCCC(O)C1 RLMGYIOTPQVQJR-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- IHYKEDLMMWGNKV-UHFFFAOYSA-N cyclopentyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1COCCN1NC=1OC(=CC=2C3=CC=CN=C3NC=2)C(=O)C=1C(=O)OC1CCCC1 IHYKEDLMMWGNKV-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- RBWXDMCMOZKIRO-UHFFFAOYSA-N cyclopropylmethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC(F)=CC=C1NC(OC(C1=O)=CC=2C3=CC=CN=C3NC=2)=C1C(=O)OCC1CC1 RBWXDMCMOZKIRO-UHFFFAOYSA-N 0.000 description 1
- GOOVIHZLFJFQPG-UHFFFAOYSA-N cyclopropylmethyl 2-[4-(2-hydroxyethoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound CC1=CC(OCCO)=CC=C1NC(OC(C1=O)=CC=2C3=CC=CN=C3NC=2)=C1C(=O)OCC1CC1 GOOVIHZLFJFQPG-UHFFFAOYSA-N 0.000 description 1
- WXJWUAFUIRHOSJ-UHFFFAOYSA-N cyclopropylmethyl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.CC1=CC(OCCN(C)C)=CC=C1NC(OC(C1=O)=CC=2C3=CC=CN=C3NC=2)=C1C(=O)OCC1CC1 WXJWUAFUIRHOSJ-UHFFFAOYSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- ZMTLYAPELCLAQU-UHFFFAOYSA-N ethyl 2-(1,1-dioxo-1,4-thiazinan-4-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCS(=O)(=O)CC1 ZMTLYAPELCLAQU-UHFFFAOYSA-N 0.000 description 1
- PQJPMXUIQAUWPL-UHFFFAOYSA-N ethyl 2-(1,1-dioxo-1,4-thiazinan-4-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCS(=O)(=O)CC1 PQJPMXUIQAUWPL-UHFFFAOYSA-N 0.000 description 1
- UAQBBDNWAFULDP-UHFFFAOYSA-N ethyl 2-(1,3-benzothiazol-6-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5SC=NC5=CC=4)=C(C3=O)C(=O)OCC)=CNC2=N1 UAQBBDNWAFULDP-UHFFFAOYSA-N 0.000 description 1
- AHKMRZKWQKUBKC-UHFFFAOYSA-N ethyl 2-(1,3-benzothiazol-6-ylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(N=CS2)C2=C1 AHKMRZKWQKUBKC-UHFFFAOYSA-N 0.000 description 1
- FNZGOLDUKPRIBS-UHFFFAOYSA-N ethyl 2-(1,3-dihydroxypropan-2-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NC(CO)CO)OC1=CC1=CNC2=NC=CC=C12 FNZGOLDUKPRIBS-UHFFFAOYSA-N 0.000 description 1
- JGGIYSNTQLQSGE-UHFFFAOYSA-N ethyl 2-(1-hydroxypropan-2-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NC(C)CO)OC1=CC1=CNC2=NC=CC=C12 JGGIYSNTQLQSGE-UHFFFAOYSA-N 0.000 description 1
- QRLRBRNKSAOPJT-UHFFFAOYSA-N ethyl 2-(1h-indazol-5-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5C=NNC5=CC=4)=C(C3=O)C(=O)OCC)=CNC2=N1 QRLRBRNKSAOPJT-UHFFFAOYSA-N 0.000 description 1
- FGZJDKNKPYRBKR-UHFFFAOYSA-N ethyl 2-(1h-indazol-6-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5NN=CC5=CC=4)=C(C3=O)C(=O)OCC)=CNC2=N1 FGZJDKNKPYRBKR-UHFFFAOYSA-N 0.000 description 1
- VCQMQPFFAAZNKC-UHFFFAOYSA-N ethyl 2-(2,2-dimethylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NN(C)C)OC1=CC1=CNC2=NC=CC=C12 VCQMQPFFAAZNKC-UHFFFAOYSA-N 0.000 description 1
- GLXQRISHKNMOOK-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1h-isoindol-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound N1CC2=CC=CC=C2C1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 GLXQRISHKNMOOK-UHFFFAOYSA-N 0.000 description 1
- KGUZCQAMAQNYDP-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1h-isoindol-1-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1C1C2=CC=CC=C2CN1 KGUZCQAMAQNYDP-UHFFFAOYSA-N 0.000 description 1
- FDRVCSJVBKGQTR-UHFFFAOYSA-N ethyl 2-(2,3-dihydroindol-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC=C2N1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 FDRVCSJVBKGQTR-UHFFFAOYSA-N 0.000 description 1
- HLLPIWAOOUISSO-UHFFFAOYSA-N ethyl 2-(2,3-dihydroxypropylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCC(O)CO)OC1=CC1=CNC2=NC=CC=C12 HLLPIWAOOUISSO-UHFFFAOYSA-N 0.000 description 1
- DQJSGBPOJBIVLV-UHFFFAOYSA-N ethyl 2-(2,4-difluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C=C1F DQJSGBPOJBIVLV-UHFFFAOYSA-N 0.000 description 1
- COXQEYRZLVIIBA-UHFFFAOYSA-N ethyl 2-(2,4-dimethoxyanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OC)C=C1OC COXQEYRZLVIIBA-UHFFFAOYSA-N 0.000 description 1
- JTTLLCLJQLSSCH-UHFFFAOYSA-N ethyl 2-(2,4-dimethoxyanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OC)C=C1OC JTTLLCLJQLSSCH-UHFFFAOYSA-N 0.000 description 1
- BDLOOGGKJOBMIB-UHFFFAOYSA-N ethyl 2-(2,6-dimethylmorpholin-4-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CC(C)OC(C)C1 BDLOOGGKJOBMIB-UHFFFAOYSA-N 0.000 description 1
- JMXFTUQIOFNKPC-UHFFFAOYSA-N ethyl 2-(2-adamantylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC4C5CC6CC(C5)CC4C6)=C(C3=O)C(=O)OCC)=CNC2=N1 JMXFTUQIOFNKPC-UHFFFAOYSA-N 0.000 description 1
- VCXSPXPBBDVEIL-UHFFFAOYSA-N ethyl 2-(2-benzoylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NNC(=O)C1=CC=CC=C1 VCXSPXPBBDVEIL-UHFFFAOYSA-N 0.000 description 1
- CUJJRMWKLNEBMD-UHFFFAOYSA-N ethyl 2-(2-chloroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1Cl CUJJRMWKLNEBMD-UHFFFAOYSA-N 0.000 description 1
- CSRCZBNWEBPCQZ-UHFFFAOYSA-N ethyl 2-(2-ethyl-2-methylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NN(C)CC)OC1=CC1=CNC2=NC=CC=C12 CSRCZBNWEBPCQZ-UHFFFAOYSA-N 0.000 description 1
- YMRSQFNEZHHTRL-UHFFFAOYSA-N ethyl 2-(2-fluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1F YMRSQFNEZHHTRL-UHFFFAOYSA-N 0.000 description 1
- NYAAABTZBKZPEI-UHFFFAOYSA-N ethyl 2-(2-hydroxy-4-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1O NYAAABTZBKZPEI-UHFFFAOYSA-N 0.000 description 1
- CUUAWUAJMBMYFI-UHFFFAOYSA-N ethyl 2-(2-hydroxy-4-methylanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1O CUUAWUAJMBMYFI-UHFFFAOYSA-N 0.000 description 1
- DFNOAGXEYVMNKV-UHFFFAOYSA-N ethyl 2-(2-hydroxyanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1O DFNOAGXEYVMNKV-UHFFFAOYSA-N 0.000 description 1
- HPWWXQPFGCCIIG-UHFFFAOYSA-N ethyl 2-(2-hydroxypropylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCC(C)O)OC1=CC1=CNC2=NC=CC=C12 HPWWXQPFGCCIIG-UHFFFAOYSA-N 0.000 description 1
- TWISMVUVDZVETA-UHFFFAOYSA-N ethyl 2-(2-methoxyanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OC TWISMVUVDZVETA-UHFFFAOYSA-N 0.000 description 1
- FUTACAOOACKJSM-UHFFFAOYSA-N ethyl 2-(2-methoxyethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCCOC)OC1=CC1=CNC2=NC=CC=C12 FUTACAOOACKJSM-UHFFFAOYSA-N 0.000 description 1
- MATMYAMSFWOBRE-UHFFFAOYSA-N ethyl 2-(2-methoxyethylamino)-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(NCCOC)OCC1=O MATMYAMSFWOBRE-UHFFFAOYSA-N 0.000 description 1
- GYVTUWIXUBJYGO-UHFFFAOYSA-N ethyl 2-(2-methyl-2-phenylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN(C)C1=CC=CC=C1 GYVTUWIXUBJYGO-UHFFFAOYSA-N 0.000 description 1
- MMSJOKQVKGSYES-UHFFFAOYSA-N ethyl 2-(2-methyl-2-phenylhydrazinyl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NN(C)C1=CC=CC=C1 MMSJOKQVKGSYES-UHFFFAOYSA-N 0.000 description 1
- YHVRQEIRMVDZSM-UHFFFAOYSA-N ethyl 2-(2-methyl-2-propan-2-ylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NN(C)C(C)C)OC1=CC1=CNC2=NC=CC=C12 YHVRQEIRMVDZSM-UHFFFAOYSA-N 0.000 description 1
- UXHVHQZCEWWVGN-UHFFFAOYSA-N ethyl 2-(2-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1C UXHVHQZCEWWVGN-UHFFFAOYSA-N 0.000 description 1
- MGOZODDTHVNMDT-UHFFFAOYSA-N ethyl 2-(2-methylanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1C MGOZODDTHVNMDT-UHFFFAOYSA-N 0.000 description 1
- IIFIDQKGJZMMCY-UHFFFAOYSA-N ethyl 2-(3,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C(F)=C1 IIFIDQKGJZMMCY-UHFFFAOYSA-N 0.000 description 1
- QOVMGLMSLQNKMO-UHFFFAOYSA-N ethyl 2-(3,4-difluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C(F)=C1 QOVMGLMSLQNKMO-UHFFFAOYSA-N 0.000 description 1
- INVQNWGZEHEYMW-UHFFFAOYSA-N ethyl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 INVQNWGZEHEYMW-UHFFFAOYSA-N 0.000 description 1
- GTPQANMSASNCDD-UHFFFAOYSA-N ethyl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CC2=CC=CC=C2CC1 GTPQANMSASNCDD-UHFFFAOYSA-N 0.000 description 1
- WSLJGCJLTMKSCJ-UHFFFAOYSA-N ethyl 2-(3,4-dimethoxyanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OC)C(OC)=C1 WSLJGCJLTMKSCJ-UHFFFAOYSA-N 0.000 description 1
- DIDUNUVUNGLZLU-UHFFFAOYSA-N ethyl 2-(3,5-dihydro-2h-1,4-benzothiazepin-4-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CSC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 DIDUNUVUNGLZLU-UHFFFAOYSA-N 0.000 description 1
- YUYFSQWXJPLOEZ-UHFFFAOYSA-N ethyl 2-(3,5-dimethylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CC(C)CC(C)C1 YUYFSQWXJPLOEZ-UHFFFAOYSA-N 0.000 description 1
- CZSOHNKWYXDPSI-UHFFFAOYSA-N ethyl 2-(3-carbamoylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(C(N)=O)C1 CZSOHNKWYXDPSI-UHFFFAOYSA-N 0.000 description 1
- TWNVMOLGWUZTTR-UHFFFAOYSA-N ethyl 2-(3-carbamoylpiperidin-1-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CC(C(N)=O)CCC1 TWNVMOLGWUZTTR-UHFFFAOYSA-N 0.000 description 1
- ODYZVGWYASXAFR-UHFFFAOYSA-N ethyl 2-(3-chloroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC(Cl)=C1 ODYZVGWYASXAFR-UHFFFAOYSA-N 0.000 description 1
- IMUYQEGREJCUGE-UHFFFAOYSA-N ethyl 2-(3-hydroxypiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC(O)C1 IMUYQEGREJCUGE-UHFFFAOYSA-N 0.000 description 1
- FJRLVLJZASXGCA-UHFFFAOYSA-N ethyl 2-(3-methoxyanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC(OC)=C1 FJRLVLJZASXGCA-UHFFFAOYSA-N 0.000 description 1
- MQQCFVHPLYYBGW-UHFFFAOYSA-N ethyl 2-(3h-benzimidazol-5-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5NC=NC5=CC=4)=C(C3=O)C(=O)OCC)=CNC2=N1 MQQCFVHPLYYBGW-UHFFFAOYSA-N 0.000 description 1
- UGRLALVSVBEJOQ-UHFFFAOYSA-N ethyl 2-(3h-benzimidazol-5-ylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(N=CN2)C2=C1 UGRLALVSVBEJOQ-UHFFFAOYSA-N 0.000 description 1
- VJGJCWJLDRNURJ-UHFFFAOYSA-N ethyl 2-(4-acetyl-1,4-diazepan-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCN(C(C)=O)CC1 VJGJCWJLDRNURJ-UHFFFAOYSA-N 0.000 description 1
- AGTSYZAWOLJQLX-UHFFFAOYSA-N ethyl 2-(4-acetylpiperazin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCN(C(C)=O)CC1 AGTSYZAWOLJQLX-UHFFFAOYSA-N 0.000 description 1
- OEFGWKNCYYKGNP-UHFFFAOYSA-N ethyl 2-(4-bromoanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(Br)C=C1 OEFGWKNCYYKGNP-UHFFFAOYSA-N 0.000 description 1
- GUZAEXKIKUZYTO-UHFFFAOYSA-N ethyl 2-(4-bromoanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(Br)C=C1 GUZAEXKIKUZYTO-UHFFFAOYSA-N 0.000 description 1
- VRLQEIKXOBGZMX-UHFFFAOYSA-N ethyl 2-(4-carbamoylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C(N)=O)C=C1 VRLQEIKXOBGZMX-UHFFFAOYSA-N 0.000 description 1
- KRJWNHKSBHBACC-UHFFFAOYSA-N ethyl 2-(4-chloroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(Cl)C=C1 KRJWNHKSBHBACC-UHFFFAOYSA-N 0.000 description 1
- PTXJDYVVRIWBRL-UHFFFAOYSA-N ethyl 2-(4-fluoro-2-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C=C1C PTXJDYVVRIWBRL-UHFFFAOYSA-N 0.000 description 1
- PYGCIIBWCHANEQ-UHFFFAOYSA-N ethyl 2-(4-fluoro-2-methylanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C=C1C PYGCIIBWCHANEQ-UHFFFAOYSA-N 0.000 description 1
- DZWKAPDMVSPJEE-UHFFFAOYSA-N ethyl 2-(4-fluoro-n-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C)C1=CC=C(F)C=C1 DZWKAPDMVSPJEE-UHFFFAOYSA-N 0.000 description 1
- DRXQAADJYGEZIE-UHFFFAOYSA-N ethyl 2-(4-fluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(F)C=C1 DRXQAADJYGEZIE-UHFFFAOYSA-N 0.000 description 1
- MJFWBGQAHYUTSS-UHFFFAOYSA-N ethyl 2-(4-hydroxy-2-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(O)C=C1C MJFWBGQAHYUTSS-UHFFFAOYSA-N 0.000 description 1
- IKZIAXLUHZJYRP-UHFFFAOYSA-N ethyl 2-(4-hydroxypiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(O)CC1 IKZIAXLUHZJYRP-UHFFFAOYSA-N 0.000 description 1
- PPLFTIGHDVRREK-UHFFFAOYSA-N ethyl 2-(4-methylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1 PPLFTIGHDVRREK-UHFFFAOYSA-N 0.000 description 1
- WQKGPKQRUSTVPE-UHFFFAOYSA-N ethyl 2-(4-methylpiperazin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCN(C)CC1 WQKGPKQRUSTVPE-UHFFFAOYSA-N 0.000 description 1
- IXSRYRNGPVTUSV-UHFFFAOYSA-N ethyl 2-(4-methylpiperazin-1-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCN(C)CC1 IXSRYRNGPVTUSV-UHFFFAOYSA-N 0.000 description 1
- FKEBEPKKNMVZFC-UHFFFAOYSA-N ethyl 2-(4-methylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(C)CC1 FKEBEPKKNMVZFC-UHFFFAOYSA-N 0.000 description 1
- KYRQUZPOCMNPQL-UHFFFAOYSA-N ethyl 2-(4-morpholin-4-ylanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C=C1)=CC=C1N1CCOCC1 KYRQUZPOCMNPQL-UHFFFAOYSA-N 0.000 description 1
- PCNKTIHZRTXCPA-UHFFFAOYSA-N ethyl 2-(4-morpholin-4-ylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(CC1)CCC1N1CCOCC1 PCNKTIHZRTXCPA-UHFFFAOYSA-N 0.000 description 1
- YFDIEPQTDBUMBD-UHFFFAOYSA-N ethyl 2-(4-morpholin-4-ylpiperidin-1-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCC(N2CCOCC2)CC1 YFDIEPQTDBUMBD-UHFFFAOYSA-N 0.000 description 1
- CQURJNSYNNFGDQ-UHFFFAOYSA-N ethyl 2-(5,7-dihydro-4h-furo[2,3-c]pyridin-6-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C1)CCC2=C1OC=C2 CQURJNSYNNFGDQ-UHFFFAOYSA-N 0.000 description 1
- XLGMUGOVWHZVGO-UHFFFAOYSA-N ethyl 2-(5,7-dihydro-4h-thieno[2,3-c]pyridin-6-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C1)CCC2=C1SC=C2 XLGMUGOVWHZVGO-UHFFFAOYSA-N 0.000 description 1
- HXYKJEKKQIDIPL-UHFFFAOYSA-N ethyl 2-(6,8-dihydro-5h-1,7-naphthyridin-7-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.C1CC2=CC=CN=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 HXYKJEKKQIDIPL-UHFFFAOYSA-N 0.000 description 1
- DOUVXIVMJMSKLI-UHFFFAOYSA-N ethyl 2-(7,8-dihydro-5h-1,6-naphthyridin-6-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.C1CC2=NC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 DOUVXIVMJMSKLI-UHFFFAOYSA-N 0.000 description 1
- OUGAGADONJPCAI-UHFFFAOYSA-N ethyl 2-(7-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=C(OC)C=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 OUGAGADONJPCAI-UHFFFAOYSA-N 0.000 description 1
- JOZIXYFXOMPEPK-UHFFFAOYSA-N ethyl 2-(8-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC(OC)=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 JOZIXYFXOMPEPK-UHFFFAOYSA-N 0.000 description 1
- KULFEJDLDHDYPK-UHFFFAOYSA-N ethyl 2-(benzylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NCC1=CC=CC=C1 KULFEJDLDHDYPK-UHFFFAOYSA-N 0.000 description 1
- RMSKWPXKMFBSSJ-UHFFFAOYSA-N ethyl 2-(cyanomethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCC#N)OC1=CC1=CNC2=NC=CC=C12 RMSKWPXKMFBSSJ-UHFFFAOYSA-N 0.000 description 1
- WUFTZTQNKCIDHC-UHFFFAOYSA-N ethyl 2-(cyclohexylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCCCC1 WUFTZTQNKCIDHC-UHFFFAOYSA-N 0.000 description 1
- OLUQUMJXISVXEM-UHFFFAOYSA-N ethyl 2-(cyclohexylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1CCCCC1 OLUQUMJXISVXEM-UHFFFAOYSA-N 0.000 description 1
- LBQFWODCSAOWHK-UHFFFAOYSA-N ethyl 2-(cyclohexylmethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1CCCCC1 LBQFWODCSAOWHK-UHFFFAOYSA-N 0.000 description 1
- IAEVEJFIEJPGKG-UHFFFAOYSA-N ethyl 2-(cyclopentylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCCC1 IAEVEJFIEJPGKG-UHFFFAOYSA-N 0.000 description 1
- PBKVOMXAISHYCT-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CC1 PBKVOMXAISHYCT-UHFFFAOYSA-N 0.000 description 1
- LBQVSTFEDLERAV-UHFFFAOYSA-N ethyl 2-(cyclopropylmethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1CC1 LBQVSTFEDLERAV-UHFFFAOYSA-N 0.000 description 1
- RSTPKMUCYICKMZ-UHFFFAOYSA-N ethyl 2-(diethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O=C1C(C(=O)OCC)=C(N(CC)CC)OC1=CC1=CNC2=NC=CC=C12 RSTPKMUCYICKMZ-UHFFFAOYSA-N 0.000 description 1
- RUDKITBNXPXJMI-UHFFFAOYSA-N ethyl 2-(diethylamino)-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(N(CC)CC)OCC1=O RUDKITBNXPXJMI-UHFFFAOYSA-N 0.000 description 1
- SJMJOHRAHTXQOE-UHFFFAOYSA-N ethyl 2-(ethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(NCC)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 SJMJOHRAHTXQOE-UHFFFAOYSA-N 0.000 description 1
- UMYWUSVBQMNKAM-UHFFFAOYSA-N ethyl 2-(ethylamino)-4-oxofuran-3-carboxylate Chemical compound CCNC1=C(C(=O)OCC)C(=O)CO1 UMYWUSVBQMNKAM-UHFFFAOYSA-N 0.000 description 1
- YBLJJUGWYINDEB-UHFFFAOYSA-N ethyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCOCC1 YBLJJUGWYINDEB-UHFFFAOYSA-N 0.000 description 1
- OPZWXHJMKMSTIS-UHFFFAOYSA-N ethyl 2-[(1-methylpiperidin-4-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1CCN(C)CC1 OPZWXHJMKMSTIS-UHFFFAOYSA-N 0.000 description 1
- ZLMVZKNYJWMGEG-UHFFFAOYSA-N ethyl 2-[(2,6-dimethylpiperidin-1-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1C(C)CCCC1C ZLMVZKNYJWMGEG-UHFFFAOYSA-N 0.000 description 1
- SPCGDHPJNPVBRM-UHFFFAOYSA-N ethyl 2-[(2-fluorophenyl)methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1=CC=CC=C1F SPCGDHPJNPVBRM-UHFFFAOYSA-N 0.000 description 1
- UOKNXSKJWVJWCH-UHFFFAOYSA-N ethyl 2-[(3-fluorophenyl)methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1=CC=CC(F)=C1 UOKNXSKJWVJWCH-UHFFFAOYSA-N 0.000 description 1
- IOGXNLLRYKBWMV-UHFFFAOYSA-N ethyl 2-[(3-hydroxypiperidin-1-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCCC(O)C1 IOGXNLLRYKBWMV-UHFFFAOYSA-N 0.000 description 1
- YTGRESPMFURJQM-UHFFFAOYSA-N ethyl 2-[(4-fluorophenyl)methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1=CC=C(F)C=C1 YTGRESPMFURJQM-UHFFFAOYSA-N 0.000 description 1
- ZDDAWQKQRHMMGY-UHFFFAOYSA-N ethyl 2-[(4-hydroxypiperidin-1-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCC(O)CC1 ZDDAWQKQRHMMGY-UHFFFAOYSA-N 0.000 description 1
- MJHOWPILRYPKJW-UHFFFAOYSA-N ethyl 2-[(4-methylpiperazin-1-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCN(C)CC1 MJHOWPILRYPKJW-UHFFFAOYSA-N 0.000 description 1
- UZXPXIWNBUOWBK-UHFFFAOYSA-N ethyl 2-[(4-methylpiperazin-1-yl)amino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NN1CCN(C)CC1 UZXPXIWNBUOWBK-UHFFFAOYSA-N 0.000 description 1
- TXENGMPXDYPSBP-UHFFFAOYSA-N ethyl 2-[2-(2-hydroxyethoxy)-4-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1OCCO TXENGMPXDYPSBP-UHFFFAOYSA-N 0.000 description 1
- AZOKNCQXTZPXBI-UHFFFAOYSA-N ethyl 2-[2-(2-methoxyethoxy)-4-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1OCCOC AZOKNCQXTZPXBI-UHFFFAOYSA-N 0.000 description 1
- IEWVHTSAERTLES-UHFFFAOYSA-N ethyl 2-[2-(2-methoxyethoxy)-4-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1OCCOC IEWVHTSAERTLES-UHFFFAOYSA-N 0.000 description 1
- PDSQYYUYIBSZIT-UHFFFAOYSA-N ethyl 2-[2-(2-methoxyethoxymethoxymethyl)piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCCC1COCOCCOC PDSQYYUYIBSZIT-UHFFFAOYSA-N 0.000 description 1
- NMKSKFRHQGNUFW-UHFFFAOYSA-N ethyl 2-[2-(2-morpholin-4-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCN1CCOCC1 NMKSKFRHQGNUFW-UHFFFAOYSA-N 0.000 description 1
- BWXFUVGNCAJBSI-UHFFFAOYSA-N ethyl 2-[2-(2-morpholin-4-ylethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCN1CCOCC1 BWXFUVGNCAJBSI-UHFFFAOYSA-N 0.000 description 1
- LHRNVGZSUKQCSU-UHFFFAOYSA-N ethyl 2-[2-(dimethylamino)ethyl-methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O=C1C(C(=O)OCC)=C(N(C)CCN(C)C)OC1=CC1=CNC2=NC=CC=C12 LHRNVGZSUKQCSU-UHFFFAOYSA-N 0.000 description 1
- VXLLXCBTMIZUTD-UHFFFAOYSA-N ethyl 2-[2-(dimethylamino)ethyl-methylamino]-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(N(C)CCN(C)C)OCC1=O VXLLXCBTMIZUTD-UHFFFAOYSA-N 0.000 description 1
- FQQOQWUUMVOMEV-UHFFFAOYSA-N ethyl 2-[2-(dimethylamino)ethylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCCN(C)C)OC1=CC1=CNC2=NC=CC=C12 FQQOQWUUMVOMEV-UHFFFAOYSA-N 0.000 description 1
- NPUZYXDHCZOSHA-UHFFFAOYSA-N ethyl 2-[2-(hydroxymethyl)piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCCC1CO NPUZYXDHCZOSHA-UHFFFAOYSA-N 0.000 description 1
- MOVWZUYSFZLTQN-UHFFFAOYSA-N ethyl 2-[2-[2-(dimethylamino)ethoxy]-4-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1OCCN(C)C MOVWZUYSFZLTQN-UHFFFAOYSA-N 0.000 description 1
- UAANZDIUJMINPM-UHFFFAOYSA-N ethyl 2-[2-[2-(dimethylamino)ethoxy]-4-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(C)C=C1OCCN(C)C UAANZDIUJMINPM-UHFFFAOYSA-N 0.000 description 1
- QWGPRJZTEZEMID-UHFFFAOYSA-N ethyl 2-[2-[2-(dimethylamino)ethoxy]anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCN(C)C QWGPRJZTEZEMID-UHFFFAOYSA-N 0.000 description 1
- VTIWHQKFAMXYPZ-UHFFFAOYSA-N ethyl 2-[2-[2-(dimethylamino)ethoxy]anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=C1OCCN(C)C VTIWHQKFAMXYPZ-UHFFFAOYSA-N 0.000 description 1
- RDVGXIPTVFJNQP-UHFFFAOYSA-N ethyl 2-[2-fluoro-4-(2-hydroxyethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCO)C=C1F RDVGXIPTVFJNQP-UHFFFAOYSA-N 0.000 description 1
- QYELDWXLTWEQBU-UHFFFAOYSA-N ethyl 2-[2-fluoro-4-(2-hydroxyethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCO)C=C1F QYELDWXLTWEQBU-UHFFFAOYSA-N 0.000 description 1
- AJAKPJCLCWVBFB-UHFFFAOYSA-N ethyl 2-[2-fluoro-4-(2-methoxyethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOC)C=C1F AJAKPJCLCWVBFB-UHFFFAOYSA-N 0.000 description 1
- JQMXGEBVVIJQOT-UHFFFAOYSA-N ethyl 2-[2-fluoro-4-(2-methoxyethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOC)C=C1F JQMXGEBVVIJQOT-UHFFFAOYSA-N 0.000 description 1
- LVAJHQWZVYRGFJ-UHFFFAOYSA-N ethyl 2-[2-hydroxyethyl(methyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(N(C)CCO)OC1=CC1=CNC2=NC=CC=C12 LVAJHQWZVYRGFJ-UHFFFAOYSA-N 0.000 description 1
- SEBXZBBJQBOQGT-UHFFFAOYSA-N ethyl 2-[2-hydroxyethyl(methyl)amino]-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(N(C)CCO)OCC1=O SEBXZBBJQBOQGT-UHFFFAOYSA-N 0.000 description 1
- WBTGCMMZVNEXLR-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(2-methylsulfanylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCSC)C=C1C WBTGCMMZVNEXLR-UHFFFAOYSA-N 0.000 description 1
- MQQZWKGEFCFBBX-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(2-methylsulfonylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCS(C)(=O)=O)C=C1C MQQZWKGEFCFBBX-UHFFFAOYSA-N 0.000 description 1
- IXUHJJOTCNYTSF-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(2-pyridin-2-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCC1=CC=CC=N1 IXUHJJOTCNYTSF-UHFFFAOYSA-N 0.000 description 1
- IDVCPWSSMYLKMB-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(2-pyrrol-1-ylethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCCN1C=CC=C1 IDVCPWSSMYLKMB-UHFFFAOYSA-N 0.000 description 1
- RFCAXZDEWUMKKB-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(3-morpholin-4-ylprop-1-ynyl)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1C#CCN1CCOCC1 RFCAXZDEWUMKKB-UHFFFAOYSA-N 0.000 description 1
- PMLBRMAZXOJCMB-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(morpholin-4-ylmethyl)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCOCC1 PMLBRMAZXOJCMB-UHFFFAOYSA-N 0.000 description 1
- SVNKUJXSMLAPNB-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyridin-2-ylmethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=CC=N1 SVNKUJXSMLAPNB-UHFFFAOYSA-N 0.000 description 1
- BANQQJWKFMUOOK-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyridin-2-ylmethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=CC=N1 BANQQJWKFMUOOK-UHFFFAOYSA-N 0.000 description 1
- DHFQSDYDROYOAS-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyridin-3-ylmethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=CN=C1 DHFQSDYDROYOAS-UHFFFAOYSA-N 0.000 description 1
- VFBYQGNVFCSFFB-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyridin-3-ylmethoxy)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=CC=CN=C1 VFBYQGNVFCSFFB-UHFFFAOYSA-N 0.000 description 1
- QBWWTXZXJZXREP-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyrimidin-2-ylmethoxy)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1OCC1=NC=CC=N1 QBWWTXZXJZXREP-UHFFFAOYSA-N 0.000 description 1
- MOYLYCWMMDNEKC-UHFFFAOYSA-N ethyl 2-[2-methyl-4-(pyrrolidin-1-ylmethyl)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCCC1 MOYLYCWMMDNEKC-UHFFFAOYSA-N 0.000 description 1
- PPJGPXWILAGSLJ-UHFFFAOYSA-N ethyl 2-[2-methyl-4-[(4-methylpiperazin-1-yl)methyl]anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCN(C)CC1 PPJGPXWILAGSLJ-UHFFFAOYSA-N 0.000 description 1
- YXUIWKJEAKYYCN-UHFFFAOYSA-N ethyl 2-[4-(2,3-dihydroxypropoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCC(O)CO)C=C1C YXUIWKJEAKYYCN-UHFFFAOYSA-N 0.000 description 1
- ZUNGMAOVEUYVHD-UHFFFAOYSA-N ethyl 2-[4-(2,3-dihydroxypropoxy)-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCC(O)CO)C=C1C ZUNGMAOVEUYVHD-UHFFFAOYSA-N 0.000 description 1
- FUARRVBCBYKCIA-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxy-2-methylpropoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCC(C)(C)O)C=C1C FUARRVBCBYKCIA-UHFFFAOYSA-N 0.000 description 1
- JZJQKWVEYCTBTI-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxyethoxy)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCO)C=C1C JZJQKWVEYCTBTI-UHFFFAOYSA-N 0.000 description 1
- SJHVOQSIOMGCOB-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxyethyl)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CCO)C=C1C SJHVOQSIOMGCOB-UHFFFAOYSA-N 0.000 description 1
- FWQRZBQNFLWDEY-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxyethyl)piperazin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCN(CCO)CC1 FWQRZBQNFLWDEY-UHFFFAOYSA-N 0.000 description 1
- WMGUIGNAFUGGPU-UHFFFAOYSA-N ethyl 2-[4-(2-hydroxyethyl)piperazin-1-yl]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCN(CCO)CC1 WMGUIGNAFUGGPU-UHFFFAOYSA-N 0.000 description 1
- RVXJQZUIMMXUOK-UHFFFAOYSA-N ethyl 2-[4-(3-hydroxyprop-1-ynyl)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C#CCO)C=C1C RVXJQZUIMMXUOK-UHFFFAOYSA-N 0.000 description 1
- FSWUCHGDPFIGOH-UHFFFAOYSA-N ethyl 2-[4-(diethylamino)piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(N(CC)CC)CC1 FSWUCHGDPFIGOH-UHFFFAOYSA-N 0.000 description 1
- GWFKJVKLZCOGPC-UHFFFAOYSA-N ethyl 2-[4-(dimethylamino)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(N(C)C)C=C1 GWFKJVKLZCOGPC-UHFFFAOYSA-N 0.000 description 1
- XNDILSHAOUCSJH-UHFFFAOYSA-N ethyl 2-[4-(dimethylamino)anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(N(C)C)C=C1 XNDILSHAOUCSJH-UHFFFAOYSA-N 0.000 description 1
- DNGDWUPAMOAANK-UHFFFAOYSA-N ethyl 2-[4-(dimethylamino)piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(N(C)C)CC1 DNGDWUPAMOAANK-UHFFFAOYSA-N 0.000 description 1
- MLHUNANKDNMWQY-UHFFFAOYSA-N ethyl 2-[4-(hydroxymethyl)anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CO)C=C1 MLHUNANKDNMWQY-UHFFFAOYSA-N 0.000 description 1
- GBZVNTRVQGEFEJ-UHFFFAOYSA-N ethyl 2-[4-(hydroxymethyl)piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(CO)CC1 GBZVNTRVQGEFEJ-UHFFFAOYSA-N 0.000 description 1
- XCIOFSUYYBMSQU-UHFFFAOYSA-N ethyl 2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]anilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(NC(=O)OC(C)(C)C)C=C1 XCIOFSUYYBMSQU-UHFFFAOYSA-N 0.000 description 1
- QAGKKTZNVIYCSX-UHFFFAOYSA-N ethyl 2-[4-[(4-hydroxypiperidin-1-yl)methyl]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1CN1CCC(O)CC1 QAGKKTZNVIYCSX-UHFFFAOYSA-N 0.000 description 1
- HZRQNQAHLAFCBG-UHFFFAOYSA-N ethyl 2-[4-[(dimethylamino)methyl]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(CN(C)C)C=C1C HZRQNQAHLAFCBG-UHFFFAOYSA-N 0.000 description 1
- JZHBMODROBRDLG-UHFFFAOYSA-N ethyl 2-[4-[2-(2-hydroxyethoxy)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOCCO)C=C1C JZHBMODROBRDLG-UHFFFAOYSA-N 0.000 description 1
- VNYVHPQCFHPGPC-UHFFFAOYSA-N ethyl 2-[4-[2-(2-hydroxyethoxy)ethoxy]-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCOCCO)C=C1C VNYVHPQCFHPGPC-UHFFFAOYSA-N 0.000 description 1
- DNWPWINHGPOBEA-UHFFFAOYSA-N ethyl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCN(C)C)C=C1C DNWPWINHGPOBEA-UHFFFAOYSA-N 0.000 description 1
- GVNCNYPHVWPIQO-UHFFFAOYSA-N ethyl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(OCCN(C)C)C=C1C GVNCNYPHVWPIQO-UHFFFAOYSA-N 0.000 description 1
- NFWRFOAWBVTPLB-UHFFFAOYSA-N ethyl 2-[4-[2-(dimethylamino)ethylamino]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;formic acid Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(NCCN(C)C)C=C1C NFWRFOAWBVTPLB-UHFFFAOYSA-N 0.000 description 1
- LLSCJGJBWQQELM-UHFFFAOYSA-N ethyl 2-[4-[2-(dimethylamino)ethylamino]-2-methylanilino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(NCCN(C)C)C=C1C LLSCJGJBWQQELM-UHFFFAOYSA-N 0.000 description 1
- FLFUSZPZSMOOMJ-UHFFFAOYSA-N ethyl 2-[4-[2-hydroxyethyl(methyl)amino]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(N(C)CCO)C=C1C FLFUSZPZSMOOMJ-UHFFFAOYSA-N 0.000 description 1
- ZNUUZQJZFNYOTN-UHFFFAOYSA-N ethyl 2-[4-[2-hydroxyethyl(methyl)amino]piperidin-1-yl]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCC(N(C)CCO)CC1 ZNUUZQJZFNYOTN-UHFFFAOYSA-N 0.000 description 1
- AAMVQWXBOZRKPY-UHFFFAOYSA-N ethyl 2-[4-[3-(4-hydroxypiperidin-1-yl)prop-1-ynyl]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C(=C1)C)=CC=C1C#CCN1CCC(O)CC1 AAMVQWXBOZRKPY-UHFFFAOYSA-N 0.000 description 1
- DYXDJLMDJMZVPI-UHFFFAOYSA-N ethyl 2-[benzyl(methyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C)CC1=CC=CC=C1 DYXDJLMDJMZVPI-UHFFFAOYSA-N 0.000 description 1
- LWUNIWLNIYIKCA-UHFFFAOYSA-N ethyl 2-[bis(2-methoxyethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(N(CCOC)CCOC)OC1=CC1=CNC2=NC=CC=C12 LWUNIWLNIYIKCA-UHFFFAOYSA-N 0.000 description 1
- MTOSYULDSATZNZ-UHFFFAOYSA-N ethyl 2-[bis(2-methoxyethyl)amino]-4-oxofuran-3-carboxylate Chemical compound CCOC(=O)C1=C(N(CCOC)CCOC)OCC1=O MTOSYULDSATZNZ-UHFFFAOYSA-N 0.000 description 1
- RTUIIVQPVVJWJQ-UHFFFAOYSA-N ethyl 2-[cyclohexyl(methyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C)C1CCCCC1 RTUIIVQPVVJWJQ-UHFFFAOYSA-N 0.000 description 1
- KNOZUKZXQAEMBE-UHFFFAOYSA-N ethyl 2-[ethyl(methyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(N(C)CC)OC1=CC1=CNC2=NC=CC=C12 KNOZUKZXQAEMBE-UHFFFAOYSA-N 0.000 description 1
- KNWCLRSQALRYTF-UHFFFAOYSA-N ethyl 2-[methyl(propan-2-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(N(C)C(C)C)OC1=CC1=CNC2=NC=CC=C12 KNWCLRSQALRYTF-UHFFFAOYSA-N 0.000 description 1
- DEGQIXSYBNOYMK-UHFFFAOYSA-N ethyl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N(C)CC1=CC=CS1 DEGQIXSYBNOYMK-UHFFFAOYSA-N 0.000 description 1
- LMXVZPYCHKDODF-UHFFFAOYSA-N ethyl 2-morpholin-4-yl-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCOCC1 LMXVZPYCHKDODF-UHFFFAOYSA-N 0.000 description 1
- OHLRLMWUFVDREV-UHFFFAOYSA-N ethyl 4-chloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CCl OHLRLMWUFVDREV-UHFFFAOYSA-N 0.000 description 1
- LUPMYBRJNMJYJT-UHFFFAOYSA-N ethyl 4-oxo-2-(1-phenylethylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C)C1=CC=CC=C1 LUPMYBRJNMJYJT-UHFFFAOYSA-N 0.000 description 1
- CJNVAHQIWPVXNT-UHFFFAOYSA-N ethyl 4-oxo-2-(1-phenylethylamino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC(C)C1=CC=CC=C1 CJNVAHQIWPVXNT-UHFFFAOYSA-N 0.000 description 1
- AWNHCJVNEYHOIZ-UHFFFAOYSA-N ethyl 4-oxo-2-(1h-pyrazol-5-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC=1C=CNN=1 AWNHCJVNEYHOIZ-UHFFFAOYSA-N 0.000 description 1
- YMAXPVBHMVSGNZ-UHFFFAOYSA-N ethyl 4-oxo-2-(1h-pyrazol-5-ylamino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=NNC=C1 YMAXPVBHMVSGNZ-UHFFFAOYSA-N 0.000 description 1
- RDXPRBOICQDUEJ-UHFFFAOYSA-N ethyl 4-oxo-2-(2-phenylethylamino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NCCC1=CC=CC=C1 RDXPRBOICQDUEJ-UHFFFAOYSA-N 0.000 description 1
- JQQKWMDUIVOUPG-UHFFFAOYSA-N ethyl 4-oxo-2-(2-piperidin-1-ylethylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCCN1CCCCC1 JQQKWMDUIVOUPG-UHFFFAOYSA-N 0.000 description 1
- VEBIKBAGNOQLGS-UHFFFAOYSA-N ethyl 4-oxo-2-(3-oxopiperazin-1-yl)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCNC(=O)C1 VEBIKBAGNOQLGS-UHFFFAOYSA-N 0.000 description 1
- OOECXNOGEWTBKX-UHFFFAOYSA-N ethyl 4-oxo-2-(4-phenylanilino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC(C=C1)=CC=C1C1=CC=CC=C1 OOECXNOGEWTBKX-UHFFFAOYSA-N 0.000 description 1
- NTYNFKXPMJXZED-UHFFFAOYSA-N ethyl 4-oxo-2-(4-propan-2-ylanilino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=C(C(C)C)C=C1 NTYNFKXPMJXZED-UHFFFAOYSA-N 0.000 description 1
- IHBCCDHFQDVFKG-UHFFFAOYSA-N ethyl 4-oxo-2-(4-propan-2-ylanilino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=C(C(C)C)C=C1 IHBCCDHFQDVFKG-UHFFFAOYSA-N 0.000 description 1
- OWUBZGOQVWTWON-UHFFFAOYSA-N ethyl 4-oxo-2-(4-propoxyanilino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC(OCCC)=CC=C1NC(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 OWUBZGOQVWTWON-UHFFFAOYSA-N 0.000 description 1
- STIYEMMYLGBYRI-UHFFFAOYSA-N ethyl 4-oxo-2-(4-propoxyanilino)furan-3-carboxylate Chemical compound C1=CC(OCCC)=CC=C1NC1=C(C(=O)OCC)C(=O)CO1 STIYEMMYLGBYRI-UHFFFAOYSA-N 0.000 description 1
- QCQLZOGPJVGEMJ-UHFFFAOYSA-N ethyl 4-oxo-2-(piperidin-1-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCCCC1 QCQLZOGPJVGEMJ-UHFFFAOYSA-N 0.000 description 1
- CSTAZHNERUZOPF-UHFFFAOYSA-N ethyl 4-oxo-2-(piperidin-1-ylamino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NN1CCCCC1 CSTAZHNERUZOPF-UHFFFAOYSA-N 0.000 description 1
- BJPDAUDWJMRYGO-UHFFFAOYSA-N ethyl 4-oxo-2-(prop-2-ynylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NCC#C)OC1=CC1=CNC2=NC=CC=C12 BJPDAUDWJMRYGO-UHFFFAOYSA-N 0.000 description 1
- FYXCKVOSHRZQPF-UHFFFAOYSA-N ethyl 4-oxo-2-(propan-2-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(NC(C)C)OC1=CC1=CNC2=NC=CC=C12 FYXCKVOSHRZQPF-UHFFFAOYSA-N 0.000 description 1
- KFFPZLVKGUPZKG-UHFFFAOYSA-N ethyl 4-oxo-2-(propan-2-ylamino)furan-3-carboxylate Chemical compound CCOC(=O)C1=C(NC(C)C)OCC1=O KFFPZLVKGUPZKG-UHFFFAOYSA-N 0.000 description 1
- JQVYTELIKNSPTP-UHFFFAOYSA-N ethyl 4-oxo-2-(pyridin-2-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CC=N1 JQVYTELIKNSPTP-UHFFFAOYSA-N 0.000 description 1
- YCWMAPZKBLANCU-UHFFFAOYSA-N ethyl 4-oxo-2-(pyridin-2-ylamino)furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1NC1=CC=CC=N1 YCWMAPZKBLANCU-UHFFFAOYSA-N 0.000 description 1
- LIFCKTCDAPUCMB-UHFFFAOYSA-N ethyl 4-oxo-2-(pyridin-3-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=CN=C1 LIFCKTCDAPUCMB-UHFFFAOYSA-N 0.000 description 1
- CUNBLKGSVPNPST-UHFFFAOYSA-N ethyl 4-oxo-2-(pyridin-4-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CC=NC=C1 CUNBLKGSVPNPST-UHFFFAOYSA-N 0.000 description 1
- SRGMIHFPDVZTDS-UHFFFAOYSA-N ethyl 4-oxo-2-(pyrimidin-5-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NC1=CN=CN=C1 SRGMIHFPDVZTDS-UHFFFAOYSA-N 0.000 description 1
- ZIXPJKZBUMZMKT-UHFFFAOYSA-N ethyl 4-oxo-2-(pyrrolidin-1-ylamino)-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCCC1 ZIXPJKZBUMZMKT-UHFFFAOYSA-N 0.000 description 1
- MUEGMPYHIZJVQY-UHFFFAOYSA-N ethyl 4-oxo-2-[(3-oxopiperazin-1-yl)amino]-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCNC(=O)C1 MUEGMPYHIZJVQY-UHFFFAOYSA-N 0.000 description 1
- PKOUTPZZOVPLIE-ZWKOTPCHSA-N ethyl 4-oxo-2-[[(1r,2s)-2-phenylcyclopropyl]amino]-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1([C@@H]2C[C@H]2NC2=C(C(C(=CC=3C4=CC=CN=C4NC=3)O2)=O)C(=O)OCC)=CC=CC=C1 PKOUTPZZOVPLIE-ZWKOTPCHSA-N 0.000 description 1
- IPBVXNACNULKOS-NWDGAFQWSA-N ethyl 4-oxo-2-[[(1r,2s)-2-phenylcyclopropyl]amino]furan-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N[C@H]1[C@H](C=2C=CC=CC=2)C1 IPBVXNACNULKOS-NWDGAFQWSA-N 0.000 description 1
- UNGVRAYQPPZUHH-UHFFFAOYSA-N ethyl 4-oxo-2-piperidin-1-yl-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCCC1 UNGVRAYQPPZUHH-UHFFFAOYSA-N 0.000 description 1
- AJYCFMCLBMEXJE-UHFFFAOYSA-N ethyl 4-oxo-2-pyrrolidin-1-yl-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1N1CCCC1 AJYCFMCLBMEXJE-UHFFFAOYSA-N 0.000 description 1
- YFZLPNSYIOZSPA-UHFFFAOYSA-N ethyl 4-oxo-2-pyrrolidin-1-ylfuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OCC)=C1N1CCCC1 YFZLPNSYIOZSPA-UHFFFAOYSA-N 0.000 description 1
- UOXAFOWNFMYCKW-UHFFFAOYSA-N ethyl 4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-(1,2,3,5-tetrahydro-1,4-benzodiazepin-4-yl)furan-3-carboxylate Chemical compound C1CNC2=CC=CC=C2CN1C(O1)=C(C(=O)OCC)C(=O)C1=CC1=CNC2=NC=CC=C12 UOXAFOWNFMYCKW-UHFFFAOYSA-N 0.000 description 1
- WLCZEXCAEZLXPP-UHFFFAOYSA-N ethyl 4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-(1,2,4-triazol-4-ylamino)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1C=NN=C1 WLCZEXCAEZLXPP-UHFFFAOYSA-N 0.000 description 1
- VSGDSHYLCJAULC-UHFFFAOYSA-N ethyl 4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-(quinolin-6-ylamino)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3OC(NC=4C=C5C=CC=NC5=CC=4)=C(C3=O)C(=O)OCC)=CNC2=N1 VSGDSHYLCJAULC-UHFFFAOYSA-N 0.000 description 1
- TVRNOBZYDVSYSM-UHFFFAOYSA-N ethyl 4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-(thiophen-2-ylmethylamino)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NCC1=CC=CS1 TVRNOBZYDVSYSM-UHFFFAOYSA-N 0.000 description 1
- DNTVXDZWVOVLOD-UHFFFAOYSA-N ethyl 4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)-2-[[4-(2,2,2-trifluoroethyl)piperazin-1-yl]amino]furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC)=C1NN1CCN(CC(F)(F)F)CC1 DNTVXDZWVOVLOD-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- ULQMKDGXIFPFQV-UHFFFAOYSA-N formic acid;(1-methylpiperidin-2-yl)methyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.CN1CCCCC1COC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 ULQMKDGXIFPFQV-UHFFFAOYSA-N 0.000 description 1
- XNZOOVISESBQKY-UHFFFAOYSA-N formic acid;(1-methylpiperidin-4-yl) 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.C1CN(C)CCC1OC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 XNZOOVISESBQKY-UHFFFAOYSA-N 0.000 description 1
- MMMRYWDLPOYNPG-UHFFFAOYSA-N formic acid;(1-methylpiperidin-4-yl)methyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.C1CN(C)CCC1COC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 MMMRYWDLPOYNPG-UHFFFAOYSA-N 0.000 description 1
- NTFDWCUVJUIIBD-UHFFFAOYSA-N formic acid;2-(4-methylpiperazin-1-yl)ethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.C1CN(C)CCN1CCOC(=O)C(C(C(=CC=1C2=CC=CN=C2NC=1)O1)=O)=C1NC1=CC=C(F)C=C1 NTFDWCUVJUIIBD-UHFFFAOYSA-N 0.000 description 1
- KQBQECFODLFPNU-UHFFFAOYSA-N formic acid;2-methylpropyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCC(C)C)=C1NC1=CC=C(F)C=C1 KQBQECFODLFPNU-UHFFFAOYSA-N 0.000 description 1
- YBJCGHJRNDWWTQ-UHFFFAOYSA-N formic acid;2-morpholin-4-ylethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.C1=CC(F)=CC=C1NC(OC(C1=O)=CC=2C3=CC=CN=C3NC=2)=C1C(=O)OCCN1CCOCC1 YBJCGHJRNDWWTQ-UHFFFAOYSA-N 0.000 description 1
- CBYYONPYJYDFCF-UHFFFAOYSA-N formic acid;2-pyrrolidin-1-ylethyl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.C1=CC(F)=CC=C1NC(OC(C1=O)=CC=2C3=CC=CN=C3NC=2)=C1C(=O)OCCN1CCCC1 CBYYONPYJYDFCF-UHFFFAOYSA-N 0.000 description 1
- YIWQHQIRMFXHGW-UHFFFAOYSA-N formic acid;propan-2-yl 2-[4-[2-(dimethylamino)ethoxy]-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound OC=O.O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1=CC=C(OCCN(C)C)C=C1C YIWQHQIRMFXHGW-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 102000052165 human CDC7 Human genes 0.000 description 1
- 102000057970 human DBF4 Human genes 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- RKDJBXYFUGOJRU-UHFFFAOYSA-N hydron;7-methoxy-1,2,3,4-tetrahydroisoquinoline;chloride Chemical compound Cl.C1CNCC2=CC(OC)=CC=C21 RKDJBXYFUGOJRU-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- BYMAWRFWNZGBIP-UHFFFAOYSA-N methyl 2-(2,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NC1=CC=C(F)C=C1F BYMAWRFWNZGBIP-UHFFFAOYSA-N 0.000 description 1
- UDOISTCJZPKWBF-UHFFFAOYSA-N methyl 2-(2,4-difluoroanilino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NC1=CC=C(F)C=C1F UDOISTCJZPKWBF-UHFFFAOYSA-N 0.000 description 1
- FYIVOOLTHVWOHP-UHFFFAOYSA-N methyl 2-(2-methoxyethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(NCCOC)=C(C(=O)OC)C(=O)C1=CC1=CNC2=NC=CC=C12 FYIVOOLTHVWOHP-UHFFFAOYSA-N 0.000 description 1
- MVXOVAYQEQXSDU-UHFFFAOYSA-N methyl 2-(cyclopropylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NC1CC1 MVXOVAYQEQXSDU-UHFFFAOYSA-N 0.000 description 1
- XSKPZZLCFMTOAC-UHFFFAOYSA-N methyl 2-(cyclopropylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NC1CC1 XSKPZZLCFMTOAC-UHFFFAOYSA-N 0.000 description 1
- IBRPAWDRAZDXHP-UHFFFAOYSA-N methyl 2-(cyclopropylmethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NCC1CC1 IBRPAWDRAZDXHP-UHFFFAOYSA-N 0.000 description 1
- KHXSLWGBXYLRFA-UHFFFAOYSA-N methyl 2-(cyclopropylmethylamino)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NCC1CC1 KHXSLWGBXYLRFA-UHFFFAOYSA-N 0.000 description 1
- LSDOHHYPDJXLOE-UHFFFAOYSA-N methyl 2-[(2-fluorophenyl)methylamino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NCC1=CC=CC=C1F LSDOHHYPDJXLOE-UHFFFAOYSA-N 0.000 description 1
- DHGANERFBQSBOC-UHFFFAOYSA-N methyl 2-[(2-fluorophenyl)methylamino]-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC)=C1NCC1=CC=CC=C1F DHGANERFBQSBOC-UHFFFAOYSA-N 0.000 description 1
- AZGFLBZQLRLLBM-UHFFFAOYSA-N methyl 2-anilino-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1NC1=CC=CC=C1 AZGFLBZQLRLLBM-UHFFFAOYSA-N 0.000 description 1
- IPTHZBOOJAVUGO-UHFFFAOYSA-N methyl 4-oxo-2-piperidin-1-yl-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC)=C1N1CCCCC1 IPTHZBOOJAVUGO-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- TTXJMSRLGMWEJZ-UHFFFAOYSA-N n-methyl-1-thiophen-2-ylmethanamine Chemical compound CNCC1=CC=CS1 TTXJMSRLGMWEJZ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- HOCZNGGYDMAETH-UHFFFAOYSA-N propan-2-yl 2-(1h-azepin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1C1=CC=CC=CN1 HOCZNGGYDMAETH-UHFFFAOYSA-N 0.000 description 1
- MZOVVTUDWNNUJK-UHFFFAOYSA-N propan-2-yl 2-(1h-azepin-2-yl)-4-oxofuran-3-carboxylate Chemical compound O1CC(=O)C(C(=O)OC(C)C)=C1C1=CC=CC=CN1 MZOVVTUDWNNUJK-UHFFFAOYSA-N 0.000 description 1
- LZUJXJMFQJESST-UHFFFAOYSA-N propan-2-yl 2-(2,2-dimethylhydrazinyl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O=C1C(C(=O)OC(C)C)=C(NN(C)C)OC1=CC1=CNC2=NC=CC=C12 LZUJXJMFQJESST-UHFFFAOYSA-N 0.000 description 1
- QDZJQSNYTZKIPW-UHFFFAOYSA-N propan-2-yl 2-(2,4-difluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1=CC=C(F)C=C1F QDZJQSNYTZKIPW-UHFFFAOYSA-N 0.000 description 1
- AXEKWDKNOSUFRH-UHFFFAOYSA-N propan-2-yl 2-(3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=CC=C2CN1C(O1)=C(C(=O)OC(C)C)C(=O)C1=CC1=CNC2=NC=CC=C12 AXEKWDKNOSUFRH-UHFFFAOYSA-N 0.000 description 1
- VSYRFYZXANWBTR-UHFFFAOYSA-N propan-2-yl 2-(4-fluoroanilino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1=CC=C(F)C=C1 VSYRFYZXANWBTR-UHFFFAOYSA-N 0.000 description 1
- BZWUHTCGLOAOCU-UHFFFAOYSA-N propan-2-yl 2-(4-methylpiperidin-1-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1N1CCC(C)CC1 BZWUHTCGLOAOCU-UHFFFAOYSA-N 0.000 description 1
- MQUCEZIEMCWLIJ-UHFFFAOYSA-N propan-2-yl 2-(6-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3C(=O)C(C(=O)OC(C)C)=C(O3)N3CC4=CC=C(C=C4CC3)OC)=CNC2=N1 MQUCEZIEMCWLIJ-UHFFFAOYSA-N 0.000 description 1
- DWWSKMAGQCADBD-UHFFFAOYSA-N propan-2-yl 2-(7-fluoro-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1CC2=CC=C(F)C=C2CN1C(O1)=C(C(=O)OC(C)C)C(=O)C1=CC1=CNC2=NC=CC=C12 DWWSKMAGQCADBD-UHFFFAOYSA-N 0.000 description 1
- OFLIKQBYLKTOMO-UHFFFAOYSA-N propan-2-yl 2-(7-methoxy-3,4-dihydro-1h-isoquinolin-2-yl)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound C1=CC=C2C(C=C3C(=O)C(C(=O)OC(C)C)=C(O3)N3CCC4=CC=C(C=C4C3)OC)=CNC2=N1 OFLIKQBYLKTOMO-UHFFFAOYSA-N 0.000 description 1
- HVOLDEWHMOJLTC-UHFFFAOYSA-N propan-2-yl 2-(cyclohexylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1CCCCC1 HVOLDEWHMOJLTC-UHFFFAOYSA-N 0.000 description 1
- ZCZBGTQHTNEIRM-UHFFFAOYSA-N propan-2-yl 2-(cyclohexylmethylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NCC1CCCCC1 ZCZBGTQHTNEIRM-UHFFFAOYSA-N 0.000 description 1
- AHWZPJUJQZBTJU-UHFFFAOYSA-N propan-2-yl 2-(cyclopropylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1CC1 AHWZPJUJQZBTJU-UHFFFAOYSA-N 0.000 description 1
- UNNTWJJPROLDQD-UHFFFAOYSA-N propan-2-yl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NN1CCOCC1 UNNTWJJPROLDQD-UHFFFAOYSA-N 0.000 description 1
- SQTLKVDNMQOIAM-UHFFFAOYSA-N propan-2-yl 2-(oxan-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1CCOCC1 SQTLKVDNMQOIAM-UHFFFAOYSA-N 0.000 description 1
- ZYJVGRGVTYFMJJ-UHFFFAOYSA-N propan-2-yl 2-[(1,1-dioxo-1,4-thiazinan-4-yl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NN1CCS(=O)(=O)CC1 ZYJVGRGVTYFMJJ-UHFFFAOYSA-N 0.000 description 1
- DJIZWVOKKRMMHB-UHFFFAOYSA-N propan-2-yl 2-[2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC(C(=C1)C)=CC=C1OCCN1CCN(C)CC1 DJIZWVOKKRMMHB-UHFFFAOYSA-N 0.000 description 1
- GOHCVRPCQGHNJD-UHFFFAOYSA-N propan-2-yl 2-[4-(2-hydroxyethylamino)-2-methylanilino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1NC1=CC=C(NCCO)C=C1C GOHCVRPCQGHNJD-UHFFFAOYSA-N 0.000 description 1
- QLUMGICXACFOCQ-UHFFFAOYSA-N propan-2-yl 2-[methyl(thiophen-2-ylmethyl)amino]-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OC(C)C)=C1N(C)CC1=CC=CS1 QLUMGICXACFOCQ-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- RSUFWHHFWMZUOV-UHFFFAOYSA-N propyl 2-(morpholin-4-ylamino)-4-oxo-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethylidene)furan-3-carboxylate Chemical compound O1C(=CC=2C3=CC=CN=C3NC=2)C(=O)C(C(=O)OCCC)=C1NN1CCOCC1 RSUFWHHFWMZUOV-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Definitions
- the present application is a reissue application of application Ser. No. 14/008,488, filed Mar. 30, 2012, which issued as U.S. Pat. No. 8,742,113, and adds new claims relative to U.S. Pat. No. 8,742,113.
- the present application is a continuation application of reissue application Ser. No. 15/172,021, filed on Jun. 2, 2016, which issued as U.S. Pat. No. RE46,815, and which is a reissue application of application Ser. No. 14/008,488, filed Mar. 30, 2012, which issued as U.S. Pat. No. 8,742,113, which is a National Stage Entry of International application No. PCT/JP2012/058636, filed Mar. 30, 2012, which claims the benefit of Japanese application No.
- the present invention relates to a medicine, particularly a novel furanone derivative having an inhibitory effect on Cdc7 or a pharmaceutically acceptable salt thereof.
- Cancer is a group of diseases caused by uncontrolled, unlimited growth of cells within a living body. Since cancer cells usually grow faster than normal cells, cancers would be capable of being treated by controlling the replication of DNA during the cell division, particularly during the division of chromosomes. Actually, gemcitabine, which has the effect of inhibiting DNA replication, is widely used in the treatment of non-small cell lung cancer, pancreatic cancer, biliary tract cancer, bladder cancer, breast cancer, ovarian cancer, or others.
- Cdc7 is a serine-threonine protein kinase and is an enzyme which is essential for the initiation of DNA replication in the cell cycle. Specifically, Cdc7 forms a complex with cofactors such as Dbf4 (ASK), and phosphorylates its substrate, MCM (mini-chromosome maintenance) proteins. It is supposed that this phosphorylation results in assembly of Cdc45 and a DNA polymerase on the DNA to form an MCM complex, thereby initiating the DNA replication (see Non Patent Literature 1). Furthermore, it has been shown in a recent study that Cdc7 plays an important role not only in the replication of DNA, but also in DNA damaging pathways (see Non Patent Literature 2).
- Cdc7 has drawn attention as a target of anticancer agents, and active researches on Cdc7 have been made.
- CDC7 is overexpressed not only in common established cell lines derived from human tumors, but also in cells taken from live tissues, such as breast cancer, colon cancer, and lung cancer (see Non Patent Literature 3).
- Non Patent Literature 3 it was shown, in more recent days, that CDC7 is overexpressed in p53-mutated triple negative (ER ⁇ /PR ⁇ /Her2 ⁇ ) breast cancer cells (see Non Patent Literature 4), and thus it has been expected that Cdc7 will be a promising target molecule against a triple negative type of breast cancer, which has been considered to be difficult to treat.
- An object of the present invention is to provide a medicine, particularly a novel furanone derivative having an inhibitory effect on Cdc7 or a pharmaceutically acceptable salt thereof.
- the present invention is achieved by the following (1) to (3):
- A represents —COOR1 or a hydrogen atom
- R1 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle
- R2 and R3 are the same or different and each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic fused ring, or an optionally substituted amino group; or alternatively, R2 and R3, taken together with the nitrogen atom to which they are attached, may form an optionally substituted heterocycle or an optionally substituted heterocyclic fused ring; and R4 represents a hydrogen atom or a halogen atom; with the proviso that when A represents —COOR1, R2 and R3 are not optionally substituted amino groups at the same time, and when A represents a hydrogen atom, R3 represents a hydrogen atom; (2) The furanone derivative or a pharmaceutically acceptable salt thereof according to (1), wherein A is —COOR1
- the present inventors have made various studies in order to solve the above-mentioned problem, and found that novel furanone derivatives represented by the formula (I) and pharmaceutically acceptable salts thereof had excellent inhibitory effect on Cdc7, resulting in completion of the present invention.
- the compounds provided by the present invention are capable of controlling the growth of cells. Therefore, the compounds of the present invention having an inhibitory effect on Cdc7 will be useful as a medicine, particularly an agent for the treatment of diseases derived from abnormal growth of cells, such as cancers.
- a novel furanone derivative of the present invention is a compound represented by the formula (I):
- A represents —COOR1 or a hydrogen atom
- R1 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle
- R2 and R3 are the same or different and each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic fused ring, or an optionally substituted amino group; or alternatively, R2 and R3, taken together with the nitrogen atom to which they are attached, may form an optionally substituted heterocycle or an optionally substituted heterocyclic fused ring; and R4 represents a hydrogen atom or a halogen atom; with the proviso that when A represents —COOR1, R2 and R3 are not optionally substituted amino groups at the same time, and when A represents a hydrogen atom, R3 represents a hydrogen atom.
- an optionally substituted hydrocarbon group includes, for example, a) a linear or branched alkyl group having 1 to 6 carbons (for example, methyl, ethyl, isopropyl, tert-butyl, hexyl, etc.); b) a linear or branched alkenyl group having 1 to 6 carbons (for example, vinyl, allyl, isopropenyl, 2-butenyl, etc.); c) an alkynyl group having 2 to 6 carbons (for example, ethynyl, propargyl, 2-butynyl, etc.); d) a cycloalkyl group having 3 to 8 carbons (for example, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.); e) a cycloalkenyl group having 3 to 8 carbons (for example, cyclohexenyl, cyclo
- the heterocyclic moiety of an optionally substituted heterocycle includes an alicyclic heterocyclic group and an aromatic heterocyclic group.
- An alicyclic heterocyclic group is, for example, a 3- to 8-membered heterocyclic group containing at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom.
- Specific examples of the alicyclic heterocyclic group include pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, etc.
- An aromatic heterocyclic group is, for example, a 5- or 6-membered monocyclic aromatic heterocyclic group containing at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom.
- Specific examples of the aromatic heterocyclic group include imidazolyl, pyrazolyl, thienyl, thiazolyl, pyridyl, etc.
- the heterocyclic fused ring moiety of an optionally substituted heterocyclic fused ring is, for example, a fused heterocyclic group which is bicyclic by fusing 3- to 8-membered rings and which contains at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom.
- a fused heterocyclic group which is bicyclic by fusing 3- to 8-membered rings and which contains at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom.
- the fused heterocyclic group include benzothiophenyl, benzimidazolyl, indazolyl, benzoxazolyl, benzothiazolyl, indolyl, isoquinolyl, phthalimide, etc.
- An optionally substituted amino group is, for example, an amino group having a linear, branched, or cyclic alkyl, aryl, or heteroaryl group which is substituted or unsubstituted and containing 1 to 6 carbons, for example, an amino group to which an alkyl group, an alkylamino group, an aryl group, a heteroaryl group, a heterocyclic group, a heterocyclic fused ring group, or the like which is unsubstituted or substituted with one or more substituents may be attached.
- the “one or more substituents” in these groups attached to an amino group may be any one or more substituents which are the same or different, unless otherwise specified, and include, for example, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted alkoxy group, an amino group, a nitro group, a cyano group, a hydroxy group, a substituted or unsubstituted alkylamino group, a carbamoyl group, a carboxyl group, a formyl group, an acetyl group, a benzoyl group, etc.
- substituted hydrocarbon group an optionally substituted heterocycle, an optionally substituted phenyl group, or an optionally substituted heterocyclic fused ring is/are be one or more substituents of any type which are allowed to be located at any chemically acceptable positions, unless otherwise specified.
- substituents may be the same or different and include, for example, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted amino group, a nitro group, a cyano group, a hydroxy group, a substituted or unsubstituted alkylamino group, a carbamoyl group, a carboxyl group, a formyl group, an acetyl group, a benzoyl group, etc.
- the heterocyclic group in the case where R2 and R3, taken together with the nitrogen atom to which they are attached, form an optionally substituted heterocycle or an optionally substituted heterocyclic fused ring is, for example, a 3- to 8-membered heterocyclic group containing at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom, or a fused alicyclic heterocyclic group which is bicyclic by fusing 3- to 8-membered rings and which contains at least one heteroatom selected from a nitrogen atom, a sulfur atom, and an oxygen atom.
- heterocyclic groups include pyrrolidinyl, piperidyl, morpholinyl, thiomorpholinyl, azepinyl, diazepinyl, dihydroisoquinolyl, tetrahydroisoquinolyl, tetrahydroquinolyl, isoindolinyl, indolinyl, tetrahydrobenzazepinyl, benzazepinyl, benzodiazepinyl, benzoxyazepinyl, benzothiazepinyl, etc.
- a halogen atom includes, for example, fluorine, chlorine, bromine, and the like.
- a compound (I) of the present invention may have isomers, for example, depending on the type of its substituents. In the specification, such a compound is sometimes described by the chemical structure of only one of its isomeric forms. However, the present invention includes all of the structurally possible isomers of such a compound (geometrical isomers, optical isomers, tautomers, etc.), and also include its individual isomers or mixtures thereof.
- the present invention encompasses stereoisomers of a compound of the present invention represented specifically by the formulae (I-Z) and (I-E), and mixtures thereof.
- a pharmaceutically acceptable salt of a compound (I) of the present invention includes a salt with an inorganic acid, such as hydrochloric acid, sulfuric acid, carbonic acid, and phosphoric acid, and a salt with an organic acid, such as formic acid, acetic acid, fumaric acid, maleic acid, methanesulfonic acid, and p-toluenesulfonic acid.
- an inorganic acid such as hydrochloric acid, sulfuric acid, carbonic acid, and phosphoric acid
- an organic acid such as formic acid, acetic acid, fumaric acid, maleic acid, methanesulfonic acid, and p-toluenesulfonic acid.
- a salt with an alkali metal such as sodium and potassium
- a salt with an alkaline earth metal such as magnesium and calcium
- a salt with an organic amine such as a lower alkyl amine and a lower alcohol amine
- a salt with a basic amino acid such as lysine, arginine, and ornithine, and in addition, an ammonium salt.
- Compounds (I) of the present invention and pharmaceutically acceptable salts thereof can be produced, for example, by the methods mentioned below.
- the production methods mentioned below when a defined group is changed under conditions where the method is performed, or when a defined group is not suitable for performing the method, the production can be easily achieved by applying methods usually used in organic synthetic chemistry, such as procedures for protection and deprotection of functional groups [T. W. Greene, Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, Inc., 1999].
- the order of reaction steps for example, those for introducing a substituent or substituents, may be changed as needed.
- a compound (Ia) wherein A is —COOR1 can be produced, for example, by scheme 1:
- R1, R2, R3 and R4 have the same meaning as mentioned above.
- a compound (Ia) of the present invention can be obtained by heating and reacting a compound (III) and 1 to 5, preferably 1 to 1.5, molar equivalents of a compound (IV) in a solvent under conditions for a Knoevenagel condensation reaction, that is, in the presence of a catalytic base such as piperidine.
- the solvent can be any solvent which is inert in the reaction, and is not limited in particular.
- a lower alcohol, preferably ethanol can be used as the solvent.
- piperidine or proline for example, can be used in an amount of from a catalytic amount to an equivalent amount relative to the compound (III).
- the reaction can be carried out in the range of from room temperature to reflux temperature and for a period of 3 hours to 2 weeks.
- the reaction can be carried out for 1 to 3 days under conditions of reflux in ethanol, thereby to synthesize the compound.
- this reaction can also be performed under other usual conditions used in the Knoevenagel condensation reaction, for example, under acidic conditions using hydrochloric acid, acetic acid, or the like, to produce the compound.
- the compound (IV) which can be used as one starting material in scheme 1 is commercially available (for example, from SIGMA-ALDRICH) or can be obtained by known methods (see, for example, Rajesh H. Bahekar et al., Bioorganic & Medicinal Chemistry, 15 (21), 6782-6795 (2007); and Seung-Jun Oh et al., Bioorganic & Medicinal Chemistry, 12 (21), 5505-5513 (2004)).
- the compound (III) which can be used as the other starting material in scheme 1 can be produced, for example, by the procedures shown in scheme 2 or 3.
- Step 2-1 wherein R1, R2, and R3 have the same meaning as mentioned above, and R1′ represents a substituted or unsubstituted lower alkyl group.
- a compound (VII) can be obtained by converting a malonic diester (V) to its enolate with a base, such as sodium hydride, in a solvent, such as anhydrous tetrahydrofuran, followed by reaction with chloroacetyl chloride (VI).
- a base such as sodium hydride
- a solvent such as anhydrous tetrahydrofuran
- the compound (III) can be obtained by reacting the compound (VII) obtained in the previous step and an amine (VIII) in an amount of from an equivalent amount to an excess amount, preferably in an amount of 1.2 to 3 molar equivalents, in a solvent at room temperature or at heated temperature.
- the solvent can be any solvent which is inert in the reaction, and is not limited in particular.
- tetrahydrofuran, dimethylformamide, ethanol, and the like can be used as the solvent.
- the reaction is dependent on the reactivity of the amine (VIII) used, and generally is completed in a period of 1 hour to 1 day at a temperature of from room temperature to the reflux temperature of the solvent.
- a base such as sodium hydride, sodium hydroxide, triethylamine, or the like, in an amount of from an equivalent amount to an excess amount.
- the compound (III) can also be produced by mean of a sequence of reactions without isolating the compound (VII), by known methods (see, for example, Sheng-Chu Kuo et al., Chem. Pharm. Bull., 36 (11), 4403-4407 (1988)) or their modified methods. That is, the compound (III) can be obtained by adding the amine (VIII) in an amount of from an equivalent amount to an excess amount, preferably in an amount of 1.2 to 3 molar equivalents, to the solution after the reaction in step 2-1, and performing the reaction at room temperature or at heated temperature.
- the malonic diester (V) and the amine (VIII) which can be used as the starting materials in scheme 2 are commercially available or can be obtained by known methods.
- R1 and R2 have the same meaning as mentioned above.
- a compound (IIIa) wherein R3 is a hydrogen atom can be produced by known methods (see, for example, Robert A. Mack et al., J. Med. Chem., 31 (10), 1910-1918 (1988)) or their modified methods. That is, the compound (IIIa) can be obtained by cyclocondensation of a compound (IX) with 1 to 5, preferably 1 to 1.5, molar equivalents of isocyanate (X) in a solvent in the presence of a base, such as triethylamine.
- the solvent can be any solvent which is inert in the reaction, and is not limited in particular.
- diethyl ether or ethyl acetate, or mixed solvents thereof can be used as the solvent.
- the reaction can be carried out in the range of from ice-cooled temperature to reflux temperature and for a period of 30 minutes to 1 day. Preferably, the reaction can be carried out at room temperature for 1 to 3 hours, thereby to synthesize the compound.
- a compound (Ia) of the present invention can also be produced by a transesterification reaction of a compound (Ia′), which is a lower alkyl ester compound, as shown in scheme 4:
- R1, R2, R3, and R4 have the same meaning as mentioned above, and R1′ represents a substituted or unsubstituted lower alkyl group.
- a compound (Ia) of the present invention can be produced by a transesterification reaction of the compound (Ia′) by known methods (see, for example, Takanori Iwasaki et al., J. Org. Chem., 73 (13), 5147-5150 (2008)) or their modified methods. That is, the compound (Ia) can be obtained by heating and reacting the compound (Ia′) and an excess amount, preferably more than 10 molar equivalents, of an alcohol (XI) in a solvent in the presence of a tetranuclear zinc cluster catalyst.
- the solvent can be any solvent which is inert in the reaction, and is not limited in particular.
- dimethylacetamide, 1,4-dioxane, diisopropyl ether, or the like can be used as the solvent.
- the alcohol (XI) may be used as the solvent.
- the tetranuclear zinc cluster catalyst catalysts which are commercially available (for example, under a product name of ZnTAC24, from STREM CHEMICALS) or are produced by the method described in the above-mentioned reference are used and added in a catalytic amount, preferably in an amount of 1 to 10% molar equivalents.
- a tertiary amine such as dimethylaminopyridine or triethylamine, is added in an amount of from a catalytic amount to 1 molar equivalent to accelerate the reaction.
- the reaction can be carried out in the range of from room temperature to reflux temperature and for a period of 1 hour to 1 week. Preferably, the reaction can be carried out for 1 to 3 days under reflux conditions, thereby to synthesize the compound. Alternatively, the reaction may also be carried out using a microwave reactor, for example, for a period of from several minutes to several hours under temperature conditions of 60 to 150° C., thereby to synthesize the compound.
- This reaction can also be carried out under other usual conditions used in the transesterification reaction, as shown in scheme 5, for example, under acidic or basic conditions, or under conditions using a catalyst, such as tetravalent titanium.
- R1′, R2, R3, and R4 have the same meaning as mentioned above.
- a compound (Ib) of the present invention can be obtained by hydrolysis of a compound (Ia′), which is a lower alkyl ester compound, under reaction conditions used in usual organic synthetic chemistry (using methods described in, for example, T. W. Greene, Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, Inc., 1999, p. 377, or their modified methods). That is, the compound (Ib) can be obtained by reacting the compound (Ia′) and a base or acid in an amount of from an equivalent amount to an excess amount in a solvent at a temperature between 0° C. and the boiling point of the solvent used.
- the solvent can be any solvent which is inert in the reaction, and is not limited in particular.
- 1,4-dioxane, tetrahydrofuran, various alcohols, or the like can be used as the solvent.
- base or acid use can be made of, for example, sodium hydroxide, potassium hydroxide, or hydrochloric acid.
- the reaction can be carried out at a temperature between 0° C. and the boiling point of the solvent used and for a period of 1 hour to 1 week. Preferably, the reaction can be carried out for 1 hour to 1 day under reflux conditions, thereby to synthesize the compound.
- R2 and R4 have the same meaning as mentioned above, and R1′′ represents a hydrogen atom or a substituted or unsubstituted lower alkyl group.
- a compound (Ic) of the present invention can be synthesized from a compound (Ia′′), which is a compound (Ia) wherein R1 is a substituted or unsubstituted lower alkyl ester group and R3 is hydrogen, using known methods (see, for example, Sheng-Chu Kuo et al., Chem. Pharm. Bull., 38 (2), 340-341 (1990)) or their modified methods.
- the reaction can be carried out by heating a solution or suspension of a compound (Ia′′) in N,N-dimethylformamide or N,N-dimethylacetamide at a temperature between 100° C. and the boiling point of the solvent used and for a period of 1 to 24 hours.
- the reaction can be carried out for 1 to 12 hours under reflux conditions, thereby to synthesize the compound.
- This reaction can also be carried out by heating and stirring in the presence of a base.
- the reaction can be carried out by heating to reflux in an alcohol solvent, such as ethanol, in the presence of a highly-concentrated aqueous solution of potassium hydroxide, thereby to synthesize compound.
- a compound (I) of the present invention which has a desired functional group at a desired position can be obtained by combining the above-mentioned methods as appropriate and carrying out procedures usually used in organic synthetic chemistry (for example, reactions for alkylation of amino groups, reactions for oxidation of an alkylthio group to the corresponding sulfoxide or sulfone group, reactions for converting an alkoxy group to a hydroxy group or vice versa).
- Compounds (I) of the present invention or pharmaceutically acceptable salts thereof can be used as medicines, particularly anti-tumor agents, in the form of conventional pharmaceutical preparations for oral administration or for parenteral administration, such as instillation.
- compositions for oral administration include solid formulations, such as tablets, granules, powders, and capsules, and liquid formulations, such as syrups. These formulations can be prepared by conventional methods. Solid formulations can be prepared using conventional pharmaceutical carriers like lactose, starches such as corn starch, crystalline cellulose such as microcrystalline cellulose, hydroxypropylcellulose, calcium carboxymethylcellulose, talc, magnesium stearate, and others. Capsules can be prepared by encapsulating the granules or powders thus prepared. Syrups can be prepared by dissolving or suspending a compound (I) of the present invention or a pharmaceutically acceptable salt thereof in an aqueous solution containing sucrose, carboxymethylcellulose, or the like.
- compositions for parenteral administration include formulations for injection, such as instillation.
- Formulations for injection can also be prepared by conventional methods, and may be incorporated in tonicity adjusting agents (for example, mannitol, sodium chloride, glucose, sorbitol, glycerol, xylitol, fructose, maltose, mannose), stabilizing agents (for example, sodium sulfite, albumin), antiseptics (for example, benzyl alcohol, methyl p-hydroxybenzoate) as appropriate.
- tonicity adjusting agents for example, mannitol, sodium chloride, glucose, sorbitol, glycerol, xylitol, fructose, maltose, mannose
- stabilizing agents for example, sodium sulfite, albumin
- antiseptics for example, benzyl alcohol, methyl p-hydroxybenzoate
- Tumors include solid tumors, such as breast cancer, colon cancer, and lung cancer, and hematological cancers, such as leukemia, lymphoma, and myeloma.
- the amount of dosage of a compound (I) of the present invention or a pharmaceutically acceptable salt thereof can be varied, according to the severeness of the disease, the age and body weight of the patient, its dosage form, and others, and usually is in the range of 1 mg to 1,000 mg per day for adult humans, which can be administered once, or twice or thrice by oral route or by parenteral route.
- Diethyl malonate (5.0 mL, 0.033 mol) was added dropwise to a solution of sodium hydride (60% w/w in oil, 2.7 g, 0.066 mol) in anhydrous tetrahydrofuran (50 mL) that cooled with ice bath. The mixture was refluxed for 5 min. The reaction mixture was cooled with ice bath, chloroacetyl chloride (2.8 mL, 0.035 mol) was added dropwise to the reaction mixture and the mixture was stirred for 1 h then stirred at 45° C. for 1 h.
- the titled compound was similarly prepared according to the procedure described in the Example 19.
- Example 2 To a solution of the compound (0.050 g, 0.13 mmol) of Example 1 in ethanol (1.0 mL), 50% potassium hydroxide solution (0.5 mL, 0.13 mmol) was added at ambient temperature. The mixture was refluxed for 1 h. Cooled to ambient temperature, the precipitate was collected by filtration, washed with ethanol. The crude material was dissolved in water (0.5 mL) and tetrahydrofuran (0.5 mL), then 2M hydrochloric acid (0.023 mL, 0.046 mmol) was added and the mixture was stirred for 30 min. The precipitate was collected by filtration, washed with water and diethyl ether then dried to afford the titled compound (0.012 g, y. 26%).
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 24.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 24.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 24.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 24.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 41, First step.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 41, First step.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 41, First step.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 41, First step.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 41, First step.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 48.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 48.
- Example 86 A solution of the compound (0.040 g, 0.10 mmol) of Example 86 and zinc cluster catalyst (Zn 4 (OCOCF 3 ) 6 O) (0.0012 g, 0.0013 mmol) in 2-propanol (0.5 mL) was stirred at 95° C. for 4 days. Cooled to ambient temperature, the reaction mixture was purified by preparative HPLC to afford the titled compound as solid (0.0061 g, y. 13%).
- Example 53 To a solution of the compound (0.20 g, 0.45 mmol) of Example 53 in ethanol (2.0 mL), aqueous 50% w/v potassium hydroxide solution (0.5 mL) was added at ambient temperature. The mixture was stirred at 95° C. for 3 h. Cooled to ambient temperature, diluted with water and conc. hydrochloric acid was added dropwise to neutralize. The precipitate was collected by filtration, washed with ethanol and diisopropyl ether then dried to afford the titled compound as solid (0.19 g, y. 98%).
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 106.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 106.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 106.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 106.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 125.
- N,N-Dimethyl-1-(3-methyl-4-nitrophenyl)methanamine (0.80 g, 4.1 mmol) was dissolved in ethanol (5.0 mL) and 10% palladium on carbon (0.18 g) was added at ambient temperature. The reaction mixture was agitated under a hydrogen atmosphere at ambient temperature for 4 h. Palladium on carbon was removed by filtration with Celite and the solvent was removed under reduced pressure to afford 4-[(dimethylamino)methyl]-2-methylaniline (0.65 g, y. 96%).
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 131.
- the titled compound (solid) was similarly prepared according to the procedure described in the Example 131.
- reaction mixture was cooled to ambient temperature then hexamethyleneimine (0.071 mL, 0.63 mmol) was added dropwise and the mixture was stirred at ambient temperature for further 1 h.
- the reaction mixture was diluted with water, and extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel, eluted with chloroform/methanol to afford 2-methoxyethyl 2-azepinyl-4-oxo-4,5-dihydrofuran-3-carboxylate as oil (0.065 g, y. 43%).
- the titled compound was similarly prepared as solid according to the procedure described in the Example 1, using ethyl 2- ⁇ [2-methyl-4-(2-pyridinylmethoxy)phenyl]amino ⁇ -4-oxo-4,5-dihydrofuran-3-carboxylate which similarly prepared according to the procedure described in the Example 74, First step to Fourth step and 7-azaindole-3-carboxaldehyde as starting materials.
- Example 74 A solution of the compound (0.032 g, 0.070 mmol) of Example 74, and zinc cluster catalyst (Zn 4 (OCOCF 3 ) 6 O) (0.0033 g, 0.0035 mmol) in n-butanol (0.5 mL) and N,N-dimethylacetamide (0.5 mL) was stirred with the microwave synthesizer (Biotage InitiatorTM) at 150° C. for 30 min. Cooled to ambient temperature, the precipitate was removed by filtration. The filtrate was purified by preparative HPLC to afford the titled compound as solid (0.015 g, y. 44%).
- the microwave synthesizer Biotage InitiatorTM
- Example 74 A solution of the compound (0.032 g, 0.070 mmol) of Example 74, and zinc cluster catalyst (Zn 4 (OCOCF 3 ) 6 O) (0.0033 g, 0.0035 mmol) in 2-propanol (0.5 mL) and N,N-dimethylacetamide (0.5 mL) was stirred with the microwave synthesizer (Biotage InitiatorTM) at 150° C. for 30 min. Cooled to ambient temperature, the precipitate was removed by filtration. The filtrate was purified by preparative HPLC to afford the titled compound as solid (0.010 g, y. 28%).
- the microwave synthesizer Biotage InitiatorTM
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/967,323 USRE48140E1 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011080185 | 2011-03-31 | ||
JP2011-080185 | 2011-03-31 | ||
US15/967,323 USRE48140E1 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
US14/008,488 US8742113B2 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
PCT/JP2012/058636 WO2012133802A1 (ja) | 2011-03-31 | 2012-03-30 | 新規フラノン誘導体 |
US201615172021A | 2016-06-02 | 2016-06-02 |
Publications (1)
Publication Number | Publication Date |
---|---|
USRE48140E1 true USRE48140E1 (en) | 2020-08-04 |
Family
ID=46931496
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/967,323 Active USRE48140E1 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
US14/008,488 Ceased US8742113B2 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
US15/172,021 Active USRE46815E1 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/008,488 Ceased US8742113B2 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
US15/172,021 Active USRE46815E1 (en) | 2011-03-31 | 2012-03-30 | Furanone derivative |
Country Status (12)
Country | Link |
---|---|
US (3) | USRE48140E1 (ja) |
EP (1) | EP2692728B1 (ja) |
JP (3) | JP5659356B2 (ja) |
KR (1) | KR101964479B1 (ja) |
CN (1) | CN103459388B (ja) |
AU (3) | AU2012233246B2 (ja) |
BR (1) | BR112013024957A2 (ja) |
CA (1) | CA2830148C (ja) |
DK (1) | DK2692728T3 (ja) |
ES (1) | ES2687450T3 (ja) |
MX (1) | MX344474B (ja) |
WO (1) | WO2012133802A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE48140E1 (en) * | 2011-03-31 | 2020-08-04 | Carna Biosciences, Inc. | Furanone derivative |
US9974795B2 (en) | 2014-01-31 | 2018-05-22 | Carna Biosciences, Inc. | Anticancer agent composition |
CN104744353B (zh) * | 2015-03-31 | 2017-11-24 | 山东友帮生化科技有限公司 | 2‑氨基‑3‑碘‑5‑氯吡啶的合成方法 |
AU2017354372A1 (en) * | 2016-11-04 | 2019-06-20 | Carna Biosciences, Inc. | Furanone derivates and methods of use thereof |
GB201807147D0 (en) | 2018-05-01 | 2018-06-13 | Oncologica Uk Ltd | Therapeutic combination |
CN113348020A (zh) * | 2018-09-24 | 2021-09-03 | 西拉肿瘤学公司 | 包括cdc7抑制剂的治疗癌症的方法 |
Citations (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001098299A1 (en) | 2000-06-19 | 2001-12-27 | Pharmacia Italia S.P.A. | Azaindole derivatives, process for their preparation, and their use as antitumor agents |
US20030158215A1 (en) | 1997-06-11 | 2003-08-21 | Peng Cho Tang | Tyrosine kinase inhibitors |
WO2004007504A1 (en) | 2002-07-17 | 2004-01-22 | Pharmacia Italia S.P.A. | Heterobicyclic pyrazole derivatives as kinase inhibitors |
WO2005009370A2 (en) | 2003-07-23 | 2005-02-03 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof and their use as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
WO2005013986A1 (en) | 2003-08-08 | 2005-02-17 | Pharmacia Italia S.P.A. | Pyridylpyrrole derivatives active as kinase inhibitors |
WO2005014572A1 (en) | 2003-08-08 | 2005-02-17 | Pharmacia Italia S.P.A. | Pyrimidylpyrrole derivatives active as kinase inhibitors |
WO2006037875A1 (fr) | 2004-10-01 | 2006-04-13 | Aventis Pharma S.A. | Nouveaux derives bis-azaindoles, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
US20070112020A1 (en) | 2005-11-11 | 2007-05-17 | Pharmacia Italia S.P.A. | Azaindolylidene derivatives as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
FR2907120A1 (fr) | 2006-10-12 | 2008-04-18 | Sanofi Aventis Sa | Nouveaux derives imidazolones,leur preparation a titre de medicaments,compositions pharmaceutiques,utilisation comme inhibiteurs de proteines kinases notamment cdc7 |
WO2008109443A2 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting cdk2 gene expression and uses thereof |
US20090298820A1 (en) | 2008-05-28 | 2009-12-03 | Wyeth | 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
WO2010030727A1 (en) | 2008-09-10 | 2010-03-18 | Wyeth Llc | 3-substituted-1h-indole, 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
WO2011008915A1 (en) | 2009-07-15 | 2011-01-20 | Abbott Laboratories | Pyrrolopyridine inhibitors of kinases |
WO2012002568A1 (en) | 2010-06-29 | 2012-01-05 | Sbi Biotech Co., Ltd. | Azaindole derivative |
US20120276093A1 (en) | 2009-11-18 | 2012-11-01 | Nerviano Medical Sciences S.R.L. | Therapeutic combination comprising a cdc7 inhibitor and an anti-neoplastic agent |
US20140018533A1 (en) | 2011-03-31 | 2014-01-16 | Carna Biosciences, Inc. | Novel furanone derivative |
US20150218138A1 (en) | 2006-03-27 | 2015-08-06 | Nerviano Medical Sciences S.R.L. | Pyridyl-and pyrimidinyl-substituted pyrrole-, thiophene- and furane-derivatives as kinase inhibitors |
US20170065609A1 (en) | 2014-01-31 | 2017-03-09 | Carna Biosciences, Inc. | Anticancer agent composition |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE388149T1 (de) * | 2004-10-14 | 2008-03-15 | Hoffmann La Roche | Neue azaindol-thiazolinone als krebsmittel |
US20060122232A1 (en) * | 2004-12-06 | 2006-06-08 | Development Center For Biotechnology | 4-Hydroxyfuroic acid derivatives |
-
2012
- 2012-03-30 US US15/967,323 patent/USRE48140E1/en active Active
- 2012-03-30 US US14/008,488 patent/US8742113B2/en not_active Ceased
- 2012-03-30 CA CA2830148A patent/CA2830148C/en active Active
- 2012-03-30 DK DK12763979.7T patent/DK2692728T3/en active
- 2012-03-30 KR KR1020137028226A patent/KR101964479B1/ko active IP Right Grant
- 2012-03-30 JP JP2013507805A patent/JP5659356B2/ja active Active
- 2012-03-30 CN CN201280015870.5A patent/CN103459388B/zh active Active
- 2012-03-30 BR BR112013024957A patent/BR112013024957A2/pt not_active IP Right Cessation
- 2012-03-30 MX MX2013010962A patent/MX344474B/es active IP Right Grant
- 2012-03-30 WO PCT/JP2012/058636 patent/WO2012133802A1/ja active Application Filing
- 2012-03-30 ES ES12763979.7T patent/ES2687450T3/es active Active
- 2012-03-30 EP EP12763979.7A patent/EP2692728B1/en active Active
- 2012-03-30 US US15/172,021 patent/USRE46815E1/en active Active
- 2012-03-30 AU AU2012233246A patent/AU2012233246B2/en active Active
-
2014
- 2014-10-28 JP JP2014219074A patent/JP5891576B2/ja active Active
-
2016
- 2016-02-05 JP JP2016020407A patent/JP6256927B2/ja active Active
-
2017
- 2017-06-13 AU AU2017203986A patent/AU2017203986B2/en active Active
-
2019
- 2019-05-17 AU AU2019203483A patent/AU2019203483A1/en not_active Abandoned
Patent Citations (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030158215A1 (en) | 1997-06-11 | 2003-08-21 | Peng Cho Tang | Tyrosine kinase inhibitors |
WO2001098299A1 (en) | 2000-06-19 | 2001-12-27 | Pharmacia Italia S.P.A. | Azaindole derivatives, process for their preparation, and their use as antitumor agents |
US6335342B1 (en) * | 2000-06-19 | 2002-01-01 | Pharmacia & Upjohn S.P.A. | Azaindole derivatives, process for their preparation, and their use as antitumor agents |
WO2004007504A1 (en) | 2002-07-17 | 2004-01-22 | Pharmacia Italia S.P.A. | Heterobicyclic pyrazole derivatives as kinase inhibitors |
WO2005009370A2 (en) | 2003-07-23 | 2005-02-03 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof and their use as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
WO2005014572A1 (en) | 2003-08-08 | 2005-02-17 | Pharmacia Italia S.P.A. | Pyrimidylpyrrole derivatives active as kinase inhibitors |
WO2005013986A1 (en) | 2003-08-08 | 2005-02-17 | Pharmacia Italia S.P.A. | Pyridylpyrrole derivatives active as kinase inhibitors |
WO2006037875A1 (fr) | 2004-10-01 | 2006-04-13 | Aventis Pharma S.A. | Nouveaux derives bis-azaindoles, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
US20070112020A1 (en) | 2005-11-11 | 2007-05-17 | Pharmacia Italia S.P.A. | Azaindolylidene derivatives as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
WO2007054508A1 (en) | 2005-11-11 | 2007-05-18 | Pfizer Italia Srl | Pyrrolopyridines as kinase inhibitors |
US20150218138A1 (en) | 2006-03-27 | 2015-08-06 | Nerviano Medical Sciences S.R.L. | Pyridyl-and pyrimidinyl-substituted pyrrole-, thiophene- and furane-derivatives as kinase inhibitors |
FR2907120A1 (fr) | 2006-10-12 | 2008-04-18 | Sanofi Aventis Sa | Nouveaux derives imidazolones,leur preparation a titre de medicaments,compositions pharmaceutiques,utilisation comme inhibiteurs de proteines kinases notamment cdc7 |
WO2008046982A2 (fr) | 2006-10-12 | 2008-04-24 | Sanofi-Aventis | Nouveaux derives imidazolones, leur preparation a titre de medicaments, compositions pharmaceutiques, utilisation comme inhibiteurs de proteines kinases notamment cdc7 |
US20090253679A1 (en) | 2006-10-12 | 2009-10-08 | Sanofi-Aventis | New imidazolone derivatives, preparation thereof as drugs, pharmaceutical compositions, and use thereof as protein kinase inhibitors, in particular cdc7 |
WO2008109443A2 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting cdk2 gene expression and uses thereof |
WO2009155052A1 (en) | 2008-05-28 | 2009-12-23 | Wyeth | 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
US20090298820A1 (en) | 2008-05-28 | 2009-12-03 | Wyeth | 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
WO2010030727A1 (en) | 2008-09-10 | 2010-03-18 | Wyeth Llc | 3-substituted-1h-indole, 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
WO2011008915A1 (en) | 2009-07-15 | 2011-01-20 | Abbott Laboratories | Pyrrolopyridine inhibitors of kinases |
US20120276093A1 (en) | 2009-11-18 | 2012-11-01 | Nerviano Medical Sciences S.R.L. | Therapeutic combination comprising a cdc7 inhibitor and an anti-neoplastic agent |
WO2012002568A1 (en) | 2010-06-29 | 2012-01-05 | Sbi Biotech Co., Ltd. | Azaindole derivative |
US20140018533A1 (en) | 2011-03-31 | 2014-01-16 | Carna Biosciences, Inc. | Novel furanone derivative |
US8742113B2 (en) | 2011-03-31 | 2014-06-03 | Sbi Biotech Co., Ltd. | Furanone derivative |
MX344474B (es) | 2011-03-31 | 2016-12-16 | Carna Biosciences Inc | Nuevos derivados de furanona. |
US20170065609A1 (en) | 2014-01-31 | 2017-03-09 | Carna Biosciences, Inc. | Anticancer agent composition |
Non-Patent Citations (14)
Title |
---|
Bonte, Dorine et al., "Cdc7-Dbf4 Kinase Overexpression in Multiple Cancers and Tumor Cell Lines is Correlated with p53 Inactiviation", Neoplasia, 2008, vol. 10, pp. 920-931. |
European Patent Office, Office Action, European Patent Application No. 12763979.7, dated Jul. 1, 2016, 4 Pages. |
Intellectual Property Australia, Examination Report, Australian Patent Application No. 2012233246, dated Apr. 4, 2016, 3 Pages. |
International Search Report of PCT/JP2012/058636, mailing date of Apr. 24, 2012. |
Iwasaki, Takanori, et al., "Transesterification of Various Methyl Esters Under Mild Conditions Catalyzed by Tetranuclear Zinc Cluster", J. Org. Chem., 2008, vol. 73, No. 13, pp. 5147-5150. |
Kim, J.M., et al., "Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint," Oncogene, 2008, pp. 3475-3482, vol. 27, No. 24. |
Kuo, Sheng-Chu et al., "Studies on Heterocyclic Compounds, IX. Synthesis and Antiallergic Activity of Furo[2,3-b][1,8]naphthyridine-3,4(2H,9H)-diones and 4H-Furo[2,3-d]pyrido[1,2-a]-pyrimidine-3,4(2H)-diones", Chem. Pharm. Bull., 1988, vol. 36, No. 11, pp. 4403-4407. |
Kuo, Sheng-Chu et al., "Studies on Heterocyclic Compounds. X. Dealkoxycarbonylation of Ethyl 2-Arylamino-4-oxo-4,5-dihydrofuran-3-carboxylates", Chem. Pharm. Bull, 1990, vol. 38, No. 2, pp. 340-341. |
Mack, Robert A. et al., "Drug-Induced Modifications of the Immune Response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic Acids and Derivatives as Novel Antiallergic Agents", J. Med. Chem., 1988, vol. 31, No. 10, pp. 1910-1918. |
Masai, Hisao et al., "Cdc7 Kinase Complex: A Key Regulator in the Initiation of DNA Replication", Journal of Cellular Physiology, 2002, vol. 190, pp. 287-296. |
Montagnoli, Alessia et al., "Cdc7 Inhibition Reveals a p53-Dependent Replication Checkpoint That Is Defective in Cancer Cells", Cancer Research, 2004, vol. 64, pp. 7110-7116. |
Patani, G.A., et al., "Bioisosterism: A Rational Approach in Drug Design," Chem. Rev., 1996, pp. 3147-3176, vol. 96. |
PCT International Search Report, International Application No. PCT/JP2012/058636, dated Apr. 24, 2012. |
Rodriguez-Acebes, Sara et al., "Targeting DNA Replication before it Starts; Cdc7 as a Therapeutic Target in p53-Mutant Breast Cancers", The American Journal of Pathology, 2010, vol. 177, pp. 2034-2045. |
Also Published As
Publication number | Publication date |
---|---|
DK2692728T3 (en) | 2018-10-08 |
CN103459388A (zh) | 2013-12-18 |
USRE46815E1 (en) | 2018-05-01 |
US20140018533A1 (en) | 2014-01-16 |
JPWO2012133802A1 (ja) | 2014-07-28 |
JP5659356B2 (ja) | 2015-01-28 |
EP2692728B1 (en) | 2018-07-04 |
JP2016084363A (ja) | 2016-05-19 |
CN103459388B (zh) | 2015-11-25 |
AU2017203986A1 (en) | 2017-07-06 |
EP2692728A1 (en) | 2014-02-05 |
KR20140056164A (ko) | 2014-05-09 |
MX2013010962A (es) | 2014-04-25 |
AU2019203483A1 (en) | 2019-06-06 |
JP6256927B2 (ja) | 2018-01-10 |
US8742113B2 (en) | 2014-06-03 |
ES2687450T3 (es) | 2018-10-25 |
EP2692728A4 (en) | 2014-08-20 |
JP5891576B2 (ja) | 2016-03-23 |
AU2012233246B2 (en) | 2017-03-30 |
AU2017203986B2 (en) | 2019-02-28 |
BR112013024957A2 (pt) | 2016-12-20 |
WO2012133802A1 (ja) | 2012-10-04 |
JP2015042663A (ja) | 2015-03-05 |
AU2012233246A1 (en) | 2013-10-10 |
CA2830148A1 (en) | 2012-10-04 |
KR101964479B1 (ko) | 2019-04-01 |
MX344474B (es) | 2016-12-16 |
CA2830148C (en) | 2020-07-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220324872A1 (en) | CDK2/4/6 Inhibitors | |
JP6256927B2 (ja) | 新規フラノン誘導体 | |
US9175010B2 (en) | Therapeutic thiophene-, furan-, and pyridine-fused azolopyrimidin-5-(6H)-ones | |
US20230391723A1 (en) | 1,4-Substituted Piperidine Derivatives | |
RU2503664C2 (ru) | Производное ацилтиомочевины или его соль, и его применение | |
JP6096792B2 (ja) | 癌治療における使用のためのモルホリニルベンゾトリアジン | |
US10239873B2 (en) | 7-azaindole or 4,7-diazaindole derivatives as IKKϵ epsilon and TBK1 inhibitor and pharmaceutical composition comprising same | |
US10280149B2 (en) | Therapeutic compounds and uses thereof | |
AU2010293429A1 (en) | 8-oxodihydropurine derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: BIG.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO SMALL (ORIGINAL EVENT CODE: SMAL); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
AS | Assignment |
Owner name: CARNA BIOSCIENCES, INC., JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SBI BIOTECH CO., LTD.;REEL/FRAME:051983/0532 Effective date: 20161109 Owner name: SBI BIOTECH CO., LTD., JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:IRIE, TAKAYUKI;SAWA, AYAKO;SAWA, MASAAKI;AND OTHERS;SIGNING DATES FROM 20130904 TO 20130911;REEL/FRAME:051983/0523 |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 8TH YR, SMALL ENTITY (ORIGINAL EVENT CODE: M2552); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY Year of fee payment: 8 |
|
CC | Certificate of correction |