SK284846B6 - Deriváty substituovaného 3-kyanochinolínu, spôsob ich prípravy, ich použitie a farmaceutický prostriedok s ich obsahom - Google Patents
Deriváty substituovaného 3-kyanochinolínu, spôsob ich prípravy, ich použitie a farmaceutický prostriedok s ich obsahom Download PDFInfo
- Publication number
- SK284846B6 SK284846B6 SK413-2001A SK4132001A SK284846B6 SK 284846 B6 SK284846 B6 SK 284846B6 SK 4132001 A SK4132001 A SK 4132001A SK 284846 B6 SK284846 B6 SK 284846B6
- Authority
- SK
- Slovakia
- Prior art keywords
- carbon atoms
- group
- mmol
- carbonitrile
- mixture
- Prior art date
Links
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title abstract description 46
- 238000002360 preparation method Methods 0.000 title abstract description 19
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 168
- -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 159
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 113
- 125000004432 carbon atom Chemical group C* 0.000 claims description 106
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 94
- 229910052757 nitrogen Inorganic materials 0.000 claims description 80
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 150000001721 carbon Chemical group 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004970 halomethyl group Chemical group 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
- 125000005605 benzo group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000004754 (C2-C12) dialkylamino group Chemical group 0.000 claims description 7
- 125000006773 (C2-C7) alkylcarbonyl group Chemical group 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 6
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 125000004149 thio group Chemical group *S* 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006766 (C2-C6) alkynyloxy group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- MJPPGVVIDGQOQT-UHFFFAOYSA-N 2-bromo-5-(2-bromo-2-nitroethenyl)furan Chemical group [O-][N+](=O)C(Br)=CC1=CC=C(Br)O1 MJPPGVVIDGQOQT-UHFFFAOYSA-N 0.000 claims 1
- QJBHXEUCZKPVEY-UHFFFAOYSA-N 2-phenoxythiophene Chemical compound C=1C=CC=CC=1OC1=CC=CS1 QJBHXEUCZKPVEY-UHFFFAOYSA-N 0.000 claims 1
- NAKXDUNGMMOTQW-UHFFFAOYSA-N 2h-tetrazole;1,3-thiazolidine Chemical compound C1CSCN1.C=1N=NNN=1 NAKXDUNGMMOTQW-UHFFFAOYSA-N 0.000 claims 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- LCIYFINKFGDAHD-UHFFFAOYSA-N azepane;3-nitrobenzoic acid Chemical group C1CCCNCC1.OC(=O)C1=CC=CC([N+]([O-])=O)=C1 LCIYFINKFGDAHD-UHFFFAOYSA-N 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 35
- 239000003814 drug Substances 0.000 abstract description 11
- 230000012010 growth Effects 0.000 abstract description 11
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 4
- 241000124008 Mammalia Species 0.000 abstract description 4
- 210000001072 colon Anatomy 0.000 abstract description 4
- 210000003238 esophagus Anatomy 0.000 abstract description 4
- 210000003734 kidney Anatomy 0.000 abstract description 4
- 210000001672 ovary Anatomy 0.000 abstract description 4
- 210000002784 stomach Anatomy 0.000 abstract description 4
- 210000003932 urinary bladder Anatomy 0.000 abstract description 4
- 210000004072 lung Anatomy 0.000 abstract description 2
- 210000000214 mouth Anatomy 0.000 abstract description 2
- 210000000867 larynx Anatomy 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 231
- 239000000203 mixture Substances 0.000 description 213
- 239000000243 solution Substances 0.000 description 206
- 150000001875 compounds Chemical class 0.000 description 204
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 186
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 148
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 146
- 238000001819 mass spectrum Methods 0.000 description 139
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 91
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- 238000010992 reflux Methods 0.000 description 82
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 73
- 239000002904 solvent Substances 0.000 description 69
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 66
- 239000000047 product Substances 0.000 description 66
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 65
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 51
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 49
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 150000003839 salts Chemical class 0.000 description 44
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Natural products O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 39
- 239000012442 inert solvent Substances 0.000 description 36
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 229910000029 sodium carbonate Inorganic materials 0.000 description 30
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 29
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 29
- 150000008064 anhydrides Chemical class 0.000 description 28
- 238000010438 heat treatment Methods 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 239000000543 intermediate Substances 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 239000005457 ice water Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 229960000583 acetic acid Drugs 0.000 description 23
- 230000005764 inhibitory process Effects 0.000 description 22
- 239000000758 substrate Substances 0.000 description 22
- 229910002092 carbon dioxide Inorganic materials 0.000 description 21
- 239000001569 carbon dioxide Substances 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- 239000003112 inhibitor Substances 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 18
- HRMLDEXYPNWNSJ-UHFFFAOYSA-N 4-chloro-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C(OCC)C(OCC)=CC2=N1 HRMLDEXYPNWNSJ-UHFFFAOYSA-N 0.000 description 18
- HMLOMVBFQJAMCN-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C(OC)C(OC)=CC2=N1 HMLOMVBFQJAMCN-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 108010055196 EphA2 Receptor Proteins 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 201000011510 cancer Diseases 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 15
- 102000043136 MAP kinase family Human genes 0.000 description 15
- 108091054455 MAP kinase family Proteins 0.000 description 15
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 238000010626 work up procedure Methods 0.000 description 15
- KEJFADGISRFLFO-UHFFFAOYSA-N 1H-indazol-6-amine Chemical compound NC1=CC=C2C=NNC2=C1 KEJFADGISRFLFO-UHFFFAOYSA-N 0.000 description 14
- 229940093475 2-ethoxyethanol Drugs 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 229960001701 chloroform Drugs 0.000 description 14
- 239000007788 liquid Substances 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 108091000080 Phosphotransferase Proteins 0.000 description 13
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 13
- 235000019270 ammonium chloride Nutrition 0.000 description 13
- 102000020233 phosphotransferase Human genes 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 12
- 235000009518 sodium iodide Nutrition 0.000 description 12
- 239000012258 stirred mixture Substances 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 11
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 11
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 11
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 150000001298 alcohols Chemical class 0.000 description 11
- 150000001735 carboxylic acids Chemical class 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 102000001301 EGF receptor Human genes 0.000 description 10
- 108060006698 EGF receptor Proteins 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 10
- 125000003277 amino group Chemical group 0.000 description 10
- 238000009835 boiling Methods 0.000 description 10
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
- 229910000024 caesium carbonate Inorganic materials 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 9
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- 229910052742 iron Inorganic materials 0.000 description 9
- 230000000144 pharmacologic effect Effects 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 9
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 8
- WMBCMCMNNWELKB-UHFFFAOYSA-N 4-chloro-7-methoxyquinoline-3-carbonitrile Chemical compound ClC1=C(C#N)C=NC2=CC(OC)=CC=C21 WMBCMCMNNWELKB-UHFFFAOYSA-N 0.000 description 8
- RUBZFZDEKLOULN-UHFFFAOYSA-N 6-aminoquinoline-3-carbonitrile Chemical compound N1=CC(C#N)=CC2=CC(N)=CC=C21 RUBZFZDEKLOULN-UHFFFAOYSA-N 0.000 description 8
- WRAPTBOWJHVKIF-UHFFFAOYSA-N 6-methoxy-4-oxo-7-phenylmethoxy-1h-quinoline-3-carbonitrile Chemical compound COC1=CC2=C(O)C(C#N)=CN=C2C=C1OCC1=CC=CC=C1 WRAPTBOWJHVKIF-UHFFFAOYSA-N 0.000 description 8
- VYXXCBNRHWHIHK-UHFFFAOYSA-N 7-(2-chloroethoxy)-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OCCCl)OC)=C1 VYXXCBNRHWHIHK-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- XSFHICWNEBCMNN-UHFFFAOYSA-N 2h-benzotriazol-5-amine Chemical compound NC1=CC=C2NN=NC2=C1 XSFHICWNEBCMNN-UHFFFAOYSA-N 0.000 description 7
- YVPONOUVXOCATL-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinoline-3-carbonitrile Chemical compound COC1=CC2=C(Cl)C(C#N)=CN=C2C=C1OCC1=CC=CC=C1 YVPONOUVXOCATL-UHFFFAOYSA-N 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- KTMGNAIGXYODKQ-VOTSOKGWSA-N ethyl (e)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(/C#N)C(=O)OCC KTMGNAIGXYODKQ-VOTSOKGWSA-N 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
- 125000006012 2-chloroethoxy group Chemical group 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000012467 final product Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- QXOXUEFXRSIYSW-UHFFFAOYSA-N methyl 3-hydroxy-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(O)=C1 QXOXUEFXRSIYSW-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229910017604 nitric acid Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 6
- 150000003248 quinolines Chemical class 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 5
- QRUCHOLKZVCUAH-UHFFFAOYSA-N 4-chloro-6-nitroquinoline-3-carbonitrile Chemical compound N1=CC(C#N)=C(Cl)C2=CC([N+](=O)[O-])=CC=C21 QRUCHOLKZVCUAH-UHFFFAOYSA-N 0.000 description 5
- 108010043945 Ephrin-A1 Proteins 0.000 description 5
- 102000020086 Ephrin-A1 Human genes 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- 101000878540 Homo sapiens Protein-tyrosine kinase 2-beta Proteins 0.000 description 5
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 230000003831 deregulation Effects 0.000 description 5
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 208000030761 polycystic kidney disease Diseases 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 125000005270 trialkylamine group Chemical group 0.000 description 5
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 4
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- JSPIITUWOZXTTO-UHFFFAOYSA-N 4-chloro-8-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC=CC2=C1Cl JSPIITUWOZXTTO-UHFFFAOYSA-N 0.000 description 4
- KCRWFINJQDRSKE-UHFFFAOYSA-N 7-ethoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound OC1=C(C#N)C=NC2=CC(OCC)=CC=C21 KCRWFINJQDRSKE-UHFFFAOYSA-N 0.000 description 4
- YWXULSPHZDNVAN-UHFFFAOYSA-N 7-ethoxy-6-nitro-4-oxo-1h-quinoline-3-carbonitrile Chemical compound C1=C(C#N)C(O)=C2C=C([N+]([O-])=O)C(OCC)=CC2=N1 YWXULSPHZDNVAN-UHFFFAOYSA-N 0.000 description 4
- BRANBXSWAAPZNW-UHFFFAOYSA-N 7-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C=2C1=CC(OC)=CC=2 BRANBXSWAAPZNW-UHFFFAOYSA-N 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- JCEPZAWNXDUVPK-UHFFFAOYSA-N 8-methoxy-6-nitro-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC([N+]([O-])=O)=CC2=C1O JCEPZAWNXDUVPK-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- QNXSIUBBGPHDDE-UHFFFAOYSA-N alpha-indanone Natural products C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 4
- 150000001409 amidines Chemical class 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- 238000009739 binding Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000000481 breast Anatomy 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 description 4
- 230000017066 negative regulation of growth Effects 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 230000002018 overexpression Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- XSXGVVNOCWAISP-VIFPVBQESA-N (2s)-2-(methoxymethyl)-1-prop-2-ynylpyrrolidine Chemical compound COC[C@@H]1CCCN1CC#C XSXGVVNOCWAISP-VIFPVBQESA-N 0.000 description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 3
- NOXAORINZJERRC-UHFFFAOYSA-N 1-methyl-4-prop-2-ynylpiperazine Chemical compound CN1CCN(CC#C)CC1 NOXAORINZJERRC-UHFFFAOYSA-N 0.000 description 3
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- PZVZGDBCMQBRMA-UHFFFAOYSA-N 3-pyridin-4-ylpropan-1-ol Chemical compound OCCCC1=CC=NC=C1 PZVZGDBCMQBRMA-UHFFFAOYSA-N 0.000 description 3
- RKXZGFHWKOWSRT-UHFFFAOYSA-N 4-(2,3-dihydro-1h-indol-6-ylamino)-6-methoxy-7-phenylmethoxyquinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NCCC4=CC=3)C(C#N)=CN=C2C=C1OCC1=CC=CC=C1 RKXZGFHWKOWSRT-UHFFFAOYSA-N 0.000 description 3
- BWFAHYBHOZFDCV-UHFFFAOYSA-N 4-(methoxymethoxy)but-2-ynoic acid Chemical compound COCOCC#CC(O)=O BWFAHYBHOZFDCV-UHFFFAOYSA-N 0.000 description 3
- XUMPXASXBIBARL-UHFFFAOYSA-N 4-chloro-5,8-dimethoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC=C(OC)C2=C1Cl XUMPXASXBIBARL-UHFFFAOYSA-N 0.000 description 3
- RLXUEEGTWNCIML-UHFFFAOYSA-N 4-chloro-6-ethoxy-7-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OC)C(OCC)=CC2=C1Cl RLXUEEGTWNCIML-UHFFFAOYSA-N 0.000 description 3
- BEGHZKYNLSIHIA-UHFFFAOYSA-N 4-chloro-7-(3-chloropropoxy)-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCCl)C(OC)=CC2=C1Cl BEGHZKYNLSIHIA-UHFFFAOYSA-N 0.000 description 3
- QIORUBTUDLGIII-UHFFFAOYSA-N 4-chloro-7-hydroxy-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(O)C(OC)=CC2=C1Cl QIORUBTUDLGIII-UHFFFAOYSA-N 0.000 description 3
- ORBNORBNTUFCFT-UHFFFAOYSA-N 5,8-dimethoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC=C(OC)C2=C1O ORBNORBNTUFCFT-UHFFFAOYSA-N 0.000 description 3
- MQGQSQDWNVXHPH-UHFFFAOYSA-N 6-ethoxy-7-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C=C(OC)C(OCC)=C2 MQGQSQDWNVXHPH-UHFFFAOYSA-N 0.000 description 3
- ROOZTGHVHGPROJ-UHFFFAOYSA-N 7-(2-chloroethoxy)-6-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCl)C(OC)=CC2=C1O ROOZTGHVHGPROJ-UHFFFAOYSA-N 0.000 description 3
- BEVFOGIUYIGEEB-UHFFFAOYSA-N 7-methoxyquinoline-3-carbonitrile Chemical compound C1=C(C#N)C=NC2=CC(OC)=CC=C21 BEVFOGIUYIGEEB-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- YXMQNJNJBCRYFJ-UHFFFAOYSA-N ClC1=C(C=NC2=CC(=C(C=C12)OCCCN1CCOCC1)OC)C#N Chemical compound ClC1=C(C=NC2=CC(=C(C=C12)OCCCN1CCOCC1)OC)C#N YXMQNJNJBCRYFJ-UHFFFAOYSA-N 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 102000009465 Growth Factor Receptors Human genes 0.000 description 3
- 108010009202 Growth Factor Receptors Proteins 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 101710122864 Major tegument protein Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 101710148592 PTS system fructose-like EIIA component Proteins 0.000 description 3
- 101710169713 PTS system fructose-specific EIIA component Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108091005682 Receptor kinases Proteins 0.000 description 3
- 101710199973 Tail tube protein Proteins 0.000 description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 3
- 238000010306 acid treatment Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 108010060350 arginyl-arginyl-leucyl-isoleucyl-glutamyl-aspartyl-alanyl-glutamyl-tyrosyl-alanyl-alanyl-arginyl-glycine Proteins 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 3
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- GYUXWAIDEGEMEE-UHFFFAOYSA-N methyl 2,3-dihydro-1,4-benzodioxine-6-carboxylate Chemical compound O1CCOC2=CC(C(=O)OC)=CC=C21 GYUXWAIDEGEMEE-UHFFFAOYSA-N 0.000 description 3
- BDUDCBNHFCERIU-UHFFFAOYSA-N methyl 2-amino-5-ethoxy-4-methoxybenzoate Chemical compound CCOC1=CC(C(=O)OC)=C(N)C=C1OC BDUDCBNHFCERIU-UHFFFAOYSA-N 0.000 description 3
- PCDOQKFPBWQJCT-UHFFFAOYSA-N methyl 3-ethoxy-4-methoxybenzoate Chemical compound CCOC1=CC(C(=O)OC)=CC=C1OC PCDOQKFPBWQJCT-UHFFFAOYSA-N 0.000 description 3
- LQVPFNOFBAQSAZ-UHFFFAOYSA-N methyl 4-(2-chloroethoxy)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OCCCl)C(OC)=C1 LQVPFNOFBAQSAZ-UHFFFAOYSA-N 0.000 description 3
- SJSPWXDMJNLLKK-UHFFFAOYSA-N methyl 4-(3-chloropropoxy)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OCCCCl)C(OC)=C1 SJSPWXDMJNLLKK-UHFFFAOYSA-N 0.000 description 3
- UMBVDMOFTQTPPF-UHFFFAOYSA-N methyl 4-(3-chloropropoxy)-5-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(OC)=C(OCCCCl)C=C1[N+]([O-])=O UMBVDMOFTQTPPF-UHFFFAOYSA-N 0.000 description 3
- JHXYNNDKQUYNFY-UHFFFAOYSA-N methyl 5-ethoxy-4-methoxy-2-nitrobenzoate Chemical compound CCOC1=CC(C(=O)OC)=C([N+]([O-])=O)C=C1OC JHXYNNDKQUYNFY-UHFFFAOYSA-N 0.000 description 3
- FOTPSTARXZXRFU-UHFFFAOYSA-N methyl 6-amino-2,3-dihydro-1,4-benzodioxine-7-carboxylate Chemical compound O1CCOC2=C1C=C(C(=O)OC)C(N)=C2 FOTPSTARXZXRFU-UHFFFAOYSA-N 0.000 description 3
- LJOUDGUKJXHDQH-UHFFFAOYSA-N methyl 6-nitro-2,3-dihydro-1,4-benzodioxine-7-carboxylate Chemical compound O1CCOC2=C1C=C(C(=O)OC)C([N+]([O-])=O)=C2 LJOUDGUKJXHDQH-UHFFFAOYSA-N 0.000 description 3
- RGUOJYYIMVSCNC-UHFFFAOYSA-N n,n-dimethylformamide;2-methylpropanoic acid Chemical compound CN(C)C=O.CC(C)C(O)=O RGUOJYYIMVSCNC-UHFFFAOYSA-N 0.000 description 3
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000000737 periodic effect Effects 0.000 description 3
- 210000003800 pharynx Anatomy 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
- MXBVNILGVJVVMH-UHFFFAOYSA-N 1,7-naphthyridine Chemical compound C1=NC=CC2=CC=CN=C21 MXBVNILGVJVVMH-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- NLHOVYMVGLRDPF-UHFFFAOYSA-N 1-oxidoquinazolin-1-ium Chemical compound C1=CC=C2[N+]([O-])=CN=CC2=C1 NLHOVYMVGLRDPF-UHFFFAOYSA-N 0.000 description 2
- OARGFWQSVACNCO-UHFFFAOYSA-N 1-oxidoquinoxalin-1-ium Chemical compound C1=CC=C2[N+]([O-])=CC=NC2=C1 OARGFWQSVACNCO-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- TXJUTRJFNRYTHH-UHFFFAOYSA-N 1h-3,1-benzoxazine-2,4-dione Chemical compound C1=CC=C2C(=O)OC(=O)NC2=C1 TXJUTRJFNRYTHH-UHFFFAOYSA-N 0.000 description 2
- BUCGXUKNUAIELU-UHFFFAOYSA-N 2,3-dihydro-1h-indol-6-amine;dihydrochloride Chemical compound [Cl-].[Cl-].[NH3+]C1=CC=C2CC[NH2+]C2=C1 BUCGXUKNUAIELU-UHFFFAOYSA-N 0.000 description 2
- KGLPWQKSKUVKMJ-UHFFFAOYSA-N 2,3-dihydrophthalazine-1,4-dione Chemical compound C1=CC=C2C(=O)NNC(=O)C2=C1 KGLPWQKSKUVKMJ-UHFFFAOYSA-N 0.000 description 2
- LZMHPPPDIPQEPV-UHFFFAOYSA-N 2-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound COc1ccc2nc(Nc3ccc4cn[nH]c4c3)c(cc2c1)C#N LZMHPPPDIPQEPV-UHFFFAOYSA-N 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
- GVBHRNIWBGTNQA-UHFFFAOYSA-N 2-methoxy-4-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N GVBHRNIWBGTNQA-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
- WNRMLIGSXULUPQ-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carbonitrile Chemical class C1=CC=C2C=C(C#N)C(=O)NC2=C1 WNRMLIGSXULUPQ-UHFFFAOYSA-N 0.000 description 2
- LGDHZCLREKIGKJ-UHFFFAOYSA-N 3,4-dimethoxyaniline Chemical compound COC1=CC=C(N)C=C1OC LGDHZCLREKIGKJ-UHFFFAOYSA-N 0.000 description 2
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 2
- VEKOZCQMIHXUDA-UHFFFAOYSA-N 3-chloro-4-(1-methylimidazol-2-yl)sulfanylaniline Chemical compound CN1C=CN=C1SC1=CC=C(N)C=C1Cl VEKOZCQMIHXUDA-UHFFFAOYSA-N 0.000 description 2
- WEZAHYDFZNTGKE-UHFFFAOYSA-N 3-ethoxyaniline Chemical compound CCOC1=CC=CC(N)=C1 WEZAHYDFZNTGKE-UHFFFAOYSA-N 0.000 description 2
- LBKFGYZQBSGRHY-UHFFFAOYSA-N 3-hydroxy-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1O LBKFGYZQBSGRHY-UHFFFAOYSA-N 0.000 description 2
- MXFNTSRVTMCEIX-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2OCOC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 MXFNTSRVTMCEIX-UHFFFAOYSA-N 0.000 description 2
- IBRBTXJKSNZSHK-UHFFFAOYSA-N 4-(1,3-benzothiazol-6-ylamino)-6,7-diethoxyquinoline-3-carbonitrile hydrochloride Chemical compound Cl.C1=C2N=CSC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 IBRBTXJKSNZSHK-UHFFFAOYSA-N 0.000 description 2
- VXBJZCVPBZPYHG-UHFFFAOYSA-N 4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)but-2-ynoic acid Chemical compound C1CN(CC#CC(=O)O)CCC21OCCO2 VXBJZCVPBZPYHG-UHFFFAOYSA-N 0.000 description 2
- RHKJQRDAZXRLRK-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-5,8-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C(OC)=CC=C(C3=NC=C2C#N)OC)=C1 RHKJQRDAZXRLRK-UHFFFAOYSA-N 0.000 description 2
- XEIXNXYVWHRHIG-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6-methoxy-7-(2-morpholin-4-ylethoxy)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCN1CCOCC1 XEIXNXYVWHRHIG-UHFFFAOYSA-N 0.000 description 2
- RITJETIJBGFZSI-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCCN1CCOCC1 RITJETIJBGFZSI-UHFFFAOYSA-N 0.000 description 2
- CZSICXGIAZSBSO-UHFFFAOYSA-N 4-(1h-indol-5-ylamino)-6-nitroquinoline-3-carbonitrile Chemical compound C1=C2NC=CC2=CC(NC2=C(C#N)C=NC3=CC=C(C=C32)[N+](=O)[O-])=C1 CZSICXGIAZSBSO-UHFFFAOYSA-N 0.000 description 2
- FJOSGPLYFUMUSV-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound O1CCOC2=CC(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OCC)OCC)=CC=C21 FJOSGPLYFUMUSV-UHFFFAOYSA-N 0.000 description 2
- CCHGREJDDRGOMA-UHFFFAOYSA-N 4-(2,3-dihydro-1H-indol-6-ylamino)-7-hydroxy-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2CCNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)O)OC)=C1 CCHGREJDDRGOMA-UHFFFAOYSA-N 0.000 description 2
- RLSJLNGPMOGTBV-UHFFFAOYSA-N 4-(2,3-dihydro-1h-indol-6-ylamino)-6-methoxy-7-(3-pyridin-4-ylpropoxy)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NCCC4=CC=3)C(C#N)=CN=C2C=C1OCCCC1=CC=NC=C1 RLSJLNGPMOGTBV-UHFFFAOYSA-N 0.000 description 2
- BPWLPDZFIUTVAK-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2N=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OCCCl)OC)=C1 BPWLPDZFIUTVAK-UHFFFAOYSA-N 0.000 description 2
- LCACCIYZPASEJC-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)but-2-ynoic acid Chemical compound CN1CCN(CC#CC(O)=O)CC1 LCACCIYZPASEJC-UHFFFAOYSA-N 0.000 description 2
- GPOHHJPOQPILBS-UHFFFAOYSA-N 4-(dimethylamino)but-2-ynoic acid Chemical compound CN(C)CC#CC(O)=O GPOHHJPOQPILBS-UHFFFAOYSA-N 0.000 description 2
- WNMBOXLSIRVMAA-UHFFFAOYSA-N 4-(isoquinolin-5-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound N1=CC=C2C(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=CC2=C1 WNMBOXLSIRVMAA-UHFFFAOYSA-N 0.000 description 2
- IOYKBTRVEQLCOW-UHFFFAOYSA-N 4-[(1,4-dioxo-2,3-dihydrophthalazin-6-yl)amino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound O=C1NNC(=O)C=2C1=CC(NC=1C(C#N)=CN=C3C=C(C(=CC3=1)OCC)OCC)=CC=2 IOYKBTRVEQLCOW-UHFFFAOYSA-N 0.000 description 2
- BYNRKWQKBHWGGE-UHFFFAOYSA-N 4-[(8-hydroxyquinolin-5-yl)amino]-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=CC=C2C(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=C(O)C2=N1 BYNRKWQKBHWGGE-UHFFFAOYSA-N 0.000 description 2
- NXTAVWSFJFKTOH-UHFFFAOYSA-N 4-[2-methoxyethyl(methyl)amino]but-2-ynoic acid Chemical compound COCCN(C)CC#CC(O)=O NXTAVWSFJFKTOH-UHFFFAOYSA-N 0.000 description 2
- YCHIMKSDNJPETL-UHFFFAOYSA-N 4-[bis(2-methoxyethyl)amino]but-2-ynoic acid Chemical compound COCCN(CCOC)CC#CC(O)=O YCHIMKSDNJPETL-UHFFFAOYSA-N 0.000 description 2
- PEVGALUKPXHMSG-UHFFFAOYSA-N 4-chloro-6,7,8-trimethoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1Cl PEVGALUKPXHMSG-UHFFFAOYSA-N 0.000 description 2
- VIKNILFXAQPQEF-UHFFFAOYSA-N 4-chloro-6-methoxyquinoline-3-carbonitrile Chemical compound N1=CC(C#N)=C(Cl)C2=CC(OC)=CC=C21 VIKNILFXAQPQEF-UHFFFAOYSA-N 0.000 description 2
- GAOYRWYHERKJQE-UHFFFAOYSA-N 4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCl)C(OC)=CC2=C1Cl GAOYRWYHERKJQE-UHFFFAOYSA-N 0.000 description 2
- QYYNVWZMCITGFR-UHFFFAOYSA-N 4-chloro-7-ethoxy-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C(OC)C(OCC)=CC2=N1 QYYNVWZMCITGFR-UHFFFAOYSA-N 0.000 description 2
- PTCUBEZCMHJCMK-UHFFFAOYSA-N 4-chloro-7-ethoxy-6-nitroquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C([N+]([O-])=O)C(OCC)=CC2=N1 PTCUBEZCMHJCMK-UHFFFAOYSA-N 0.000 description 2
- JTNOADATUOSXCU-UHFFFAOYSA-N 4-chloro-7-methoxy-6-nitroquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C([N+]([O-])=O)C(OC)=CC2=N1 JTNOADATUOSXCU-UHFFFAOYSA-N 0.000 description 2
- QEYAMZRQGHAJKB-UHFFFAOYSA-N 4-chloro-8-methoxy-6-nitroquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=CC([N+]([O-])=O)=CC2=C1Cl QEYAMZRQGHAJKB-UHFFFAOYSA-N 0.000 description 2
- RBNLMAXLHADNEU-UHFFFAOYSA-N 4-oxo-1h-quinoline-3-carbonitrile Chemical compound C1=CC=C2C(=O)C(C#N)=CNC2=C1 RBNLMAXLHADNEU-UHFFFAOYSA-N 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
- QTRNLGSLYVLFAW-UHFFFAOYSA-N 6,7,8-trimethoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1O QTRNLGSLYVLFAW-UHFFFAOYSA-N 0.000 description 2
- RHZWXKPCVURCIH-UHFFFAOYSA-N 6,7-diethoxy-4-(1h-indazol-6-ylamino)quinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 RHZWXKPCVURCIH-UHFFFAOYSA-N 0.000 description 2
- VZJDHPYFCBLKGI-UHFFFAOYSA-N 6,7-dimethoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C=C(OC)C(OC)=C2 VZJDHPYFCBLKGI-UHFFFAOYSA-N 0.000 description 2
- NQVAAWNLOZNKOX-UHFFFAOYSA-N 6-ethoxy-4-(1h-indazol-6-ylamino)-7-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OC)OCC)=C1 NQVAAWNLOZNKOX-UHFFFAOYSA-N 0.000 description 2
- TUVSLUWYBFYQLA-UHFFFAOYSA-N 7-(3-chloropropoxy)-6-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCCl)C(OC)=CC2=C1O TUVSLUWYBFYQLA-UHFFFAOYSA-N 0.000 description 2
- XYYZLOVSXBIDIM-UHFFFAOYSA-N 7-ethoxy-6-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C=C(OCC)C(OC)=C2 XYYZLOVSXBIDIM-UHFFFAOYSA-N 0.000 description 2
- KTZRTSATHWBRBI-UHFFFAOYSA-N 7-methoxy-6-nitro-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C=C(OC)C([N+]([O-])=O)=C2 KTZRTSATHWBRBI-UHFFFAOYSA-N 0.000 description 2
- PPOYMBZZLRCTCT-UHFFFAOYSA-N 8-methoxy-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=C1C(OC)=CC=C2 PPOYMBZZLRCTCT-UHFFFAOYSA-N 0.000 description 2
- QEUDZAMKDJMSRO-UHFFFAOYSA-N 9-chloro-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline-8-carbonitrile Chemical compound O1CCOC2=C1C=C1N=CC(C#N)=C(Cl)C1=C2 QEUDZAMKDJMSRO-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OVMUDRVDJIECDW-UHFFFAOYSA-N COCCOC1=CC2=CC(=C(N=C2C=C1OCCOC)NC3=CC4=C(C=C3)C=NN4)C#N Chemical compound COCCOC1=CC2=CC(=C(N=C2C=C1OCCOC)NC3=CC4=C(C=C3)C=NN4)C#N OVMUDRVDJIECDW-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- RZIAABRFQASVSW-UHFFFAOYSA-N Isoquinoline N-oxide Chemical compound C1=CC=CC2=C[N+]([O-])=CC=C21 RZIAABRFQASVSW-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical compound C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- LUEHNHVFDCZTGL-UHFFFAOYSA-N but-2-ynoic acid Chemical compound CC#CC(O)=O LUEHNHVFDCZTGL-UHFFFAOYSA-N 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 2
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
- UIOISEYUJOHZNT-UHFFFAOYSA-N ethyl 2-cyano-3-(2-methyl-4-nitrophenyl)prop-2-enoate Chemical compound CCOC(=O)C(C#N)=CC1=CC=C([N+]([O-])=O)C=C1C UIOISEYUJOHZNT-UHFFFAOYSA-N 0.000 description 2
- UDIHMWWUBNTTKL-UHFFFAOYSA-N ethyl 2-cyano-3-(3,4-dimethoxyanilino)prop-2-enoate Chemical compound CCOC(=O)C(C#N)=CNC1=CC=C(OC)C(OC)=C1 UDIHMWWUBNTTKL-UHFFFAOYSA-N 0.000 description 2
- CRIVSDDAATXAGJ-UHFFFAOYSA-N ethyl 2-cyano-3-(4-nitroanilino)prop-2-enoate Chemical compound CCOC(=O)C(C#N)=CNC1=CC=C([N+]([O-])=O)C=C1 CRIVSDDAATXAGJ-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000008241 heterogeneous mixture Substances 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 2
- 210000000088 lip Anatomy 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical group CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 2
- 229940087646 methanolamine Drugs 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- STIXSFPLHFQZNA-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)-4-ethoxy-5-methoxybenzoate Chemical compound CCOC1=CC(N=CN(C)C)=C(C(=O)OC)C=C1OC STIXSFPLHFQZNA-UHFFFAOYSA-N 0.000 description 2
- WIUQTTCGYDCFAS-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)-5-methoxy-4-phenylmethoxybenzoate Chemical compound C1=C(N=CN(C)C)C(C(=O)OC)=CC(OC)=C1OCC1=CC=CC=C1 WIUQTTCGYDCFAS-UHFFFAOYSA-N 0.000 description 2
- OWQMAKRMHORJCK-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)benzoate Chemical compound COC(=O)C1=CC=CC=C1N=CN(C)C OWQMAKRMHORJCK-UHFFFAOYSA-N 0.000 description 2
- OKYLJMNWFOOEKE-UHFFFAOYSA-N methyl 2-amino-4-(2-chloroethoxy)-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=C(OCCCl)C=C1N OKYLJMNWFOOEKE-UHFFFAOYSA-N 0.000 description 2
- ZQWYDHOFFKWQAC-UHFFFAOYSA-N methyl 2-amino-4-ethoxy-5-methoxybenzoate Chemical compound CCOC1=CC(N)=C(C(=O)OC)C=C1OC ZQWYDHOFFKWQAC-UHFFFAOYSA-N 0.000 description 2
- DFJJAQKKQNIWOC-UHFFFAOYSA-N methyl 2-amino-4-methoxy-5-(3-morpholin-4-ylpropoxy)benzoate Chemical compound C1=C(N)C(C(=O)OC)=CC(OCCCN2CCOCC2)=C1OC DFJJAQKKQNIWOC-UHFFFAOYSA-N 0.000 description 2
- AXZCWNLUZBSALR-UHFFFAOYSA-N methyl 4-(2-chloroethoxy)-5-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(OC)=C(OCCCl)C=C1[N+]([O-])=O AXZCWNLUZBSALR-UHFFFAOYSA-N 0.000 description 2
- HVLQOCXAZMSAPT-UHFFFAOYSA-N methyl 4-ethoxy-3-methoxybenzoate Chemical compound CCOC1=CC=C(C(=O)OC)C=C1OC HVLQOCXAZMSAPT-UHFFFAOYSA-N 0.000 description 2
- ACWQHKOWQNOPIB-UHFFFAOYSA-N methyl 4-ethoxy-5-methoxy-2-nitrobenzoate Chemical compound CCOC1=CC([N+]([O-])=O)=C(C(=O)OC)C=C1OC ACWQHKOWQNOPIB-UHFFFAOYSA-N 0.000 description 2
- CKQJPOFVWCMVGK-UHFFFAOYSA-N methyl 4-methoxy-3-(3-morpholin-4-ylpropoxy)benzoate Chemical compound COC(=O)C1=CC=C(OC)C(OCCCN2CCOCC2)=C1 CKQJPOFVWCMVGK-UHFFFAOYSA-N 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- ZFLBJYJRXLWTJI-UHFFFAOYSA-N n-(2-methoxyethyl)-n-methylpropan-2-amine Chemical compound COCCN(C)C(C)C ZFLBJYJRXLWTJI-UHFFFAOYSA-N 0.000 description 2
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229940080469 phosphocellulose Drugs 0.000 description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- 229940126731 protein tyrosine phosphatase inhibitor Drugs 0.000 description 2
- 239000003806 protein tyrosine phosphatase inhibitor Substances 0.000 description 2
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 2
- TYLGVQVJCVFREB-UHFFFAOYSA-N pyrido[3,4-b]pyrazine Chemical compound C1=NC=CC2=NC=CN=C21 TYLGVQVJCVFREB-UHFFFAOYSA-N 0.000 description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 2
- 239000008259 solid foam Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 2
- 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 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- NQQRXZOPZBKCNF-NSCUHMNNSA-N (e)-but-2-enamide Chemical compound C\C=C\C(N)=O NQQRXZOPZBKCNF-NSCUHMNNSA-N 0.000 description 1
- 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 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
- KRUCRVZSHWOMHC-UHFFFAOYSA-N 1,1-dioxo-1-benzothiophen-6-amine Chemical compound NC1=CC=C2C=CS(=O)(=O)C2=C1 KRUCRVZSHWOMHC-UHFFFAOYSA-N 0.000 description 1
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- XGNXYCFREOZBOL-UHFFFAOYSA-N 1,3-benzodioxol-5-amine Chemical compound NC1=CC=C2OCOC2=C1 XGNXYCFREOZBOL-UHFFFAOYSA-N 0.000 description 1
- FAYAYUOZWYJNBD-UHFFFAOYSA-N 1,3-benzothiazol-6-amine Chemical compound NC1=CC=C2N=CSC2=C1 FAYAYUOZWYJNBD-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 1
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
- ZCCPVTVGEQLONB-UHFFFAOYSA-N 1-(1,3-dioxolan-2-yl)-n-methylmethanamine Chemical compound CNCC1OCCO1 ZCCPVTVGEQLONB-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
- MBLOVZIAFQVXIN-UHFFFAOYSA-N 1-(bromomethyl)-2-chloro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CBr)C(Cl)=C1 MBLOVZIAFQVXIN-UHFFFAOYSA-N 0.000 description 1
- BBKQRTBYEIDUFY-UHFFFAOYSA-N 1-[(2-chloro-4-nitrophenyl)methyl]imidazole Chemical compound ClC1=CC([N+](=O)[O-])=CC=C1CN1C=NC=C1 BBKQRTBYEIDUFY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FRJNKYGTHPUSJR-UHFFFAOYSA-N 1-benzothiophene 1,1-dioxide Chemical compound C1=CC=C2S(=O)(=O)C=CC2=C1 FRJNKYGTHPUSJR-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
- XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 1
- MIMYTSWNVBMNRH-UHFFFAOYSA-N 1h-indol-6-amine Chemical compound NC1=CC=C2C=CNC2=C1 MIMYTSWNVBMNRH-UHFFFAOYSA-N 0.000 description 1
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
- JWZQJTGQFHIRFQ-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carboxylic acid Chemical compound O1CCOC2=CC(C(=O)O)=CC=C21 JWZQJTGQFHIRFQ-UHFFFAOYSA-N 0.000 description 1
- LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 1
- PSOZMUMWCXLRKX-UHFFFAOYSA-N 2,4-dinitro-6-pentan-2-ylphenol Chemical compound CCCC(C)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O PSOZMUMWCXLRKX-UHFFFAOYSA-N 0.000 description 1
- OWQRWYWUZLMGKD-UHFFFAOYSA-N 2-(3-chloropropoxy)-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C(C#N)C(OCCCCl)=NC3=CC=C(C=C32)OC)=C1 OWQRWYWUZLMGKD-UHFFFAOYSA-N 0.000 description 1
- IHJOQFXXQGYWMJ-UHFFFAOYSA-N 2-(4-amino-2-chlorophenyl)sulfanyl-1h-quinazolin-4-one Chemical compound ClC1=CC(N)=CC=C1SC1=NC2=CC=CC=C2C(=O)N1 IHJOQFXXQGYWMJ-UHFFFAOYSA-N 0.000 description 1
- GGFWRHHSJHEHFX-UHFFFAOYSA-N 2-(dimethylamino)but-2-enamide Chemical compound CN(C)C(C(=O)N)=CC GGFWRHHSJHEHFX-UHFFFAOYSA-N 0.000 description 1
- YQZZJSAAELHVAX-UHFFFAOYSA-N 2-[2-[4-(2-hydroxyethyl)piperazin-1-yl]ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound N#CC1=C(NC=2C=C3NN=CC3=CC=2)C2=CC(OC)=CC=C2N=C1OCCN1CCN(CCO)CC1 YQZZJSAAELHVAX-UHFFFAOYSA-N 0.000 description 1
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 1
- RRQMXQWSIJERLR-UHFFFAOYSA-N 2-amino-3,6-dimethoxybenzoic acid Chemical compound COC1=CC=C(OC)C(C(O)=O)=C1N RRQMXQWSIJERLR-UHFFFAOYSA-N 0.000 description 1
- ZXNMIUJDTOMBPV-UHFFFAOYSA-N 2-chloroethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCl)C=C1 ZXNMIUJDTOMBPV-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 1
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 1
- ZNIGVBCUUZGYDU-UHFFFAOYSA-N 2-methyl-1,3-benzothiazol-5-amine;dihydrochloride Chemical compound [Cl-].[Cl-].[NH3+]C1=CC=C2SC(C)=[NH+]C2=C1 ZNIGVBCUUZGYDU-UHFFFAOYSA-N 0.000 description 1
- UJYKXBDYOPPOCY-UHFFFAOYSA-N 2-methyl-3h-benzimidazol-5-amine Chemical compound C1=C(N)C=C2NC(C)=NC2=C1 UJYKXBDYOPPOCY-UHFFFAOYSA-N 0.000 description 1
- XTTIQGSLJBWVIV-UHFFFAOYSA-N 2-methyl-4-nitroaniline Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N XTTIQGSLJBWVIV-UHFFFAOYSA-N 0.000 description 1
- RNVCVTLRINQCPJ-VJJZLTLGSA-N 2-methylaniline Chemical group CC1=CC=CC=C1[15NH2] RNVCVTLRINQCPJ-VJJZLTLGSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-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
- 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
- CXBMZBDYEDCGKC-UHFFFAOYSA-N 3-chloro-4-(1,3-thiazol-2-ylsulfanyl)aniline Chemical compound ClC1=CC(N)=CC=C1SC1=NC=CS1 CXBMZBDYEDCGKC-UHFFFAOYSA-N 0.000 description 1
- TYKICIVELAQYGM-UHFFFAOYSA-N 3-chloro-4-(4-methylpyrimidin-2-yl)sulfanylaniline Chemical compound CC1=CC=NC(SC=2C(=CC(N)=CC=2)Cl)=N1 TYKICIVELAQYGM-UHFFFAOYSA-N 0.000 description 1
- NQCQVNHLNXCSPY-UHFFFAOYSA-N 3-chloropropyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCl)C=C1 NQCQVNHLNXCSPY-UHFFFAOYSA-N 0.000 description 1
- SXOPCLUOUFQBJV-UHFFFAOYSA-N 3-methoxyanthranilic acid Chemical compound COC1=CC=CC(C(O)=O)=C1N SXOPCLUOUFQBJV-UHFFFAOYSA-N 0.000 description 1
- OCVLSHAVSIYKLI-UHFFFAOYSA-N 3h-1,3-thiazole-2-thione Chemical compound SC1=NC=CS1 OCVLSHAVSIYKLI-UHFFFAOYSA-N 0.000 description 1
- WFRXSXUDWCVSPI-UHFFFAOYSA-N 3h-benzimidazol-5-amine Chemical compound NC1=CC=C2NC=NC2=C1 WFRXSXUDWCVSPI-UHFFFAOYSA-N 0.000 description 1
- TVXVKHGYFDHAET-UHFFFAOYSA-N 4-(1h-indazol-5-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2NN=CC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OC)OC)=C1 TVXVKHGYFDHAET-UHFFFAOYSA-N 0.000 description 1
- OMSAOAKIZAHJQS-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6-methoxy-7-(2-thiomorpholin-4-ylethoxy)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCN1CCSCC1 OMSAOAKIZAHJQS-UHFFFAOYSA-N 0.000 description 1
- AHWYMPQEOLBIJR-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]quinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCN1CCN(C)CC1 AHWYMPQEOLBIJR-UHFFFAOYSA-N 0.000 description 1
- BJYQPZAVSHQNCD-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C(C#N)C=NC3=CC=C(C=C32)OC)=C1 BJYQPZAVSHQNCD-UHFFFAOYSA-N 0.000 description 1
- YCWUBHDUEWEJDO-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile;hydrochloride Chemical compound Cl.COC1=CC2=NC=C(C#N)C(NC=3C=C4NN=CC4=CC=3)=C2C=C1OCCCN1CCOCC1 YCWUBHDUEWEJDO-UHFFFAOYSA-N 0.000 description 1
- ANCMEMUICRYIKS-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-7-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C3=CC=C(C=C3N=CC=2C#N)OC)=C1 ANCMEMUICRYIKS-UHFFFAOYSA-N 0.000 description 1
- NGKIUYTYCDGUQN-UHFFFAOYSA-N 4-(1h-indazol-6-ylamino)-8-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=CC=C(C3=NC=C2C#N)OC)=C1 NGKIUYTYCDGUQN-UHFFFAOYSA-N 0.000 description 1
- CBCKPWFSIFRZCL-UHFFFAOYSA-N 4-(1h-indol-4-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=CC2=C1C=CN2 CBCKPWFSIFRZCL-UHFFFAOYSA-N 0.000 description 1
- BKVDWYDOKDMLQD-UHFFFAOYSA-N 4-(1h-indol-5-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C2NC=CC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OC)OC)=C1 BKVDWYDOKDMLQD-UHFFFAOYSA-N 0.000 description 1
- WDZXAWAANRQCGP-UHFFFAOYSA-N 4-(1h-indol-5-ylamino)-7-methoxyquinoline-3-carbonitrile Chemical compound C1=C2NC=CC2=CC(NC=2C3=CC=C(C=C3N=CC=2C#N)OC)=C1 WDZXAWAANRQCGP-UHFFFAOYSA-N 0.000 description 1
- PPPRTLJONJRQEW-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound O1CCOC2=CC(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=C21 PPPRTLJONJRQEW-UHFFFAOYSA-N 0.000 description 1
- IRYNXXKQLIQSNU-UHFFFAOYSA-N 4-(2,3-dihydro-1h-inden-5-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2CCCC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 IRYNXXKQLIQSNU-UHFFFAOYSA-N 0.000 description 1
- WBFSZZFPFIBEKO-UHFFFAOYSA-N 4-(2,3-dihydro-1h-indol-6-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2CCNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 WBFSZZFPFIBEKO-UHFFFAOYSA-N 0.000 description 1
- ZGAUPBQKIBZFHD-UHFFFAOYSA-N 4-(2-methoxyethoxy)but-2-ynoic acid Chemical compound COCCOCC#CC(O)=O ZGAUPBQKIBZFHD-UHFFFAOYSA-N 0.000 description 1
- GDMGDNKXZKMWTF-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2NN=NC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 GDMGDNKXZKMWTF-UHFFFAOYSA-N 0.000 description 1
- JWMBVLJKYAGLMR-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2N=NNC2=CC(NC2=C(C#N)C=NC3=CC=C(C=C32)OC)=C1 JWMBVLJKYAGLMR-UHFFFAOYSA-N 0.000 description 1
- AMNZDZLZSGVOSM-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile;hydrochloride Chemical compound Cl.COC1=CC2=NC=C(C#N)C(NC=3C=C4N=NNC4=CC=3)=C2C=C1OCCCN1CCOCC1 AMNZDZLZSGVOSM-UHFFFAOYSA-N 0.000 description 1
- LRJJIBAPQUCPPE-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-7-methoxyquinoline-3-carbonitrile Chemical compound C1=CC2=NNN=C2C=C1NC1=C(C#N)C=NC2=CC(OC)=CC=C21 LRJJIBAPQUCPPE-UHFFFAOYSA-N 0.000 description 1
- BQPYRSRITIQRBG-UHFFFAOYSA-N 4-(2h-benzotriazol-5-ylamino)-8-methoxyquinoline-3-carbonitrile Chemical compound C1=C2N=NNC2=CC(NC2=C3C=CC=C(C3=NC=C2C#N)OC)=C1 BQPYRSRITIQRBG-UHFFFAOYSA-N 0.000 description 1
- PIAZYBLGBSMNLX-UHFFFAOYSA-N 4-(3-chloropropyl)morpholine Chemical compound ClCCCN1CCOCC1 PIAZYBLGBSMNLX-UHFFFAOYSA-N 0.000 description 1
- UPNHCRXYRMEMCJ-UHFFFAOYSA-N 4-(4-benzylanilino)-6-methoxy-7-[2-(triazol-1-yl)ethoxy]quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCN3N=NC=C3)C(OC)=CC2=C1NC(C=C1)=CC=C1CC1=CC=CC=C1 UPNHCRXYRMEMCJ-UHFFFAOYSA-N 0.000 description 1
- YLUGQOCWOPDIMD-UHFFFAOYSA-N 4-(dimethylamino)but-2-enamide Chemical compound CN(C)CC=CC(N)=O YLUGQOCWOPDIMD-UHFFFAOYSA-N 0.000 description 1
- LUNUNJFSHKSXGQ-UHFFFAOYSA-N 4-Aminoindole Chemical compound NC1=CC=CC2=C1C=CN2 LUNUNJFSHKSXGQ-UHFFFAOYSA-N 0.000 description 1
- UTUNYHCFJRINPD-UHFFFAOYSA-N 4-[(1,1-dioxo-1-benzothiophen-6-yl)amino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2C=CS(=O)(=O)C2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 UTUNYHCFJRINPD-UHFFFAOYSA-N 0.000 description 1
- COSYWMZOAGREHD-UHFFFAOYSA-N 4-[(1,3-dioxoisoindol-5-yl)amino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C1=C2C(=O)NC(=O)C2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 COSYWMZOAGREHD-UHFFFAOYSA-N 0.000 description 1
- HLWFPOYNIAGJIK-UHFFFAOYSA-N 4-[(2,4-dioxo-1h-3,1-benzoxazin-6-yl)amino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound N1C(=O)OC(=O)C2=CC(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OCC)OCC)=CC=C21 HLWFPOYNIAGJIK-UHFFFAOYSA-N 0.000 description 1
- SSZLDEGEMCYNDX-UHFFFAOYSA-N 4-[(4-chloronaphthalen-1-yl)amino]-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=CC=C2C(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=C(Cl)C2=C1 SSZLDEGEMCYNDX-UHFFFAOYSA-N 0.000 description 1
- CNSPCGJFXFXSNP-UHFFFAOYSA-N 4-[(4-phenyl-1,3-thiazol-2-yl)sulfanyl]-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1SC1=NC(C=2C=CC=CC=2)=CS1 CNSPCGJFXFXSNP-UHFFFAOYSA-N 0.000 description 1
- GVWXQEVWTJEGNA-UHFFFAOYSA-N 4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-6,7-diethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1SC1=NC=CN1C GVWXQEVWTJEGNA-UHFFFAOYSA-N 0.000 description 1
- ZPEPSYOVJOCFBL-UHFFFAOYSA-N 4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(OC)C(OC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1SC1=NC=CN1C ZPEPSYOVJOCFBL-UHFFFAOYSA-N 0.000 description 1
- DQWNUCNHLIZZKQ-UHFFFAOYSA-N 4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-6-nitroquinoline-3-carbonitrile Chemical compound CN1C=CN=C1SC(C(=C1)Cl)=CC=C1NC1=C(C#N)C=NC2=CC=C([N+]([O-])=O)C=C12 DQWNUCNHLIZZKQ-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 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 1
- QPYOVDHMXSEVCP-UHFFFAOYSA-N 4-chloro-5,6-bis(2-methoxyethoxy)quinoline-3-carbonitrile Chemical compound N1=CC(C#N)=C(Cl)C2=C(OCCOC)C(OCCOC)=CC=C21 QPYOVDHMXSEVCP-UHFFFAOYSA-N 0.000 description 1
- BPEDILCALKIVRC-UHFFFAOYSA-N 4-chloro-6-methoxy-7-(3-pyridin-4-ylpropoxy)quinoline-3-carbonitrile Chemical compound COC1=CC2=C(Cl)C(C#N)=CN=C2C=C1OCCCC1=CC=NC=C1 BPEDILCALKIVRC-UHFFFAOYSA-N 0.000 description 1
- OPAVQHRMPKMRFQ-UHFFFAOYSA-N 4-chloro-8-methyl-6-nitroquinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C(C)=CC([N+]([O-])=O)=CC2=C1Cl OPAVQHRMPKMRFQ-UHFFFAOYSA-N 0.000 description 1
- DEPDZGNUVOAZCW-UHFFFAOYSA-N 4-chloronaphthalen-1-amine Chemical compound C1=CC=C2C(N)=CC=C(Cl)C2=C1 DEPDZGNUVOAZCW-UHFFFAOYSA-N 0.000 description 1
- HCXMIOZRXOIQHX-UHFFFAOYSA-N 4-chloroquinoline-3-carbonitrile Chemical class C1=CC=C2C(Cl)=C(C#N)C=NC2=C1 HCXMIOZRXOIQHX-UHFFFAOYSA-N 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- SODWJACROGQSMM-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalen-1-amine Chemical compound C1CCCC2=C1C=CC=C2N SODWJACROGQSMM-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
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 1
- QWCQIVFJQVQFHH-UHFFFAOYSA-N 6,7-diethoxy-4-(1h-indol-6-ylamino)quinoline-3-carbonitrile Chemical compound C1=C2C=CNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 QWCQIVFJQVQFHH-UHFFFAOYSA-N 0.000 description 1
- UGOPZNISTHWGHW-UHFFFAOYSA-N 6,7-diethoxy-4-[(1-methyl-2,5-dioxo-3,4-dihydro-1,4-benzodiazepin-7-yl)amino]quinoline-3-carbonitrile Chemical compound CN1C(=O)CNC(=O)C2=CC(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OCC)OCC)=CC=C21 UGOPZNISTHWGHW-UHFFFAOYSA-N 0.000 description 1
- YCRZFANDTCRLLT-UHFFFAOYSA-N 6,7-diethoxy-4-[(1-oxo-2,3-dihydroinden-5-yl)amino]quinoline-3-carbonitrile Chemical compound C1=C2C(=O)CCC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 YCRZFANDTCRLLT-UHFFFAOYSA-N 0.000 description 1
- YYUDBPBJKDGFNN-UHFFFAOYSA-N 6,7-diethoxy-4-[(3-oxo-1h-2-benzofuran-5-yl)amino]quinoline-3-carbonitrile Chemical compound C1=C2COC(=O)C2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OCC)OCC)=C1 YYUDBPBJKDGFNN-UHFFFAOYSA-N 0.000 description 1
- SKWITGADMHWLHT-UHFFFAOYSA-N 6,7-diethoxy-4-[(4-methyl-2-oxochromen-7-yl)amino]quinoline-3-carbonitrile Chemical compound CC1=CC(=O)OC2=CC(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OCC)OCC)=CC=C21 SKWITGADMHWLHT-UHFFFAOYSA-N 0.000 description 1
- KKDPSZLBMSZVEO-UHFFFAOYSA-N 6,7-dimethoxy-4-(quinolin-5-ylamino)quinoline-3-carbonitrile Chemical compound C1=CC=C2C(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=CC2=N1 KKDPSZLBMSZVEO-UHFFFAOYSA-N 0.000 description 1
- AZZNBKGDUSZEML-UHFFFAOYSA-N 6,7-dimethoxy-4-(quinolin-8-ylamino)quinoline-3-carbonitrile Chemical compound C1=CN=C2C(NC=3C(C#N)=CN=C4C=C(C(=CC4=3)OC)OC)=CC=CC2=C1 AZZNBKGDUSZEML-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
- UOJCPAAEKXNPQT-UHFFFAOYSA-N 6-amino-2,3-dihydroinden-1-one Chemical compound NC1=CC=C2CCC(=O)C2=C1 UOJCPAAEKXNPQT-UHFFFAOYSA-N 0.000 description 1
- CLYCLRFHPKKUBR-UHFFFAOYSA-N 6-amino-3h-1,3-benzothiazol-2-one Chemical compound NC1=CC=C2N=C(O)SC2=C1 CLYCLRFHPKKUBR-UHFFFAOYSA-N 0.000 description 1
- ZIJZDNKZJZUROE-UHFFFAOYSA-N 6-amino-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2COC(=O)C2=C1 ZIJZDNKZJZUROE-UHFFFAOYSA-N 0.000 description 1
- HGIUIIMTOJWDHY-UHFFFAOYSA-N 6-amino-4-(1h-indol-5-ylamino)quinoline-3-carbonitrile Chemical compound C1=C2NC=CC2=CC(NC2=C(C#N)C=NC3=CC=C(C=C32)N)=C1 HGIUIIMTOJWDHY-UHFFFAOYSA-N 0.000 description 1
- LOPQLRVLRXSZPG-UHFFFAOYSA-N 6-amino-4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]quinoline-3-carbonitrile Chemical compound CN1C=CN=C1SC(C(=C1)Cl)=CC=C1NC1=C(C#N)C=NC2=CC=C(N)C=C12 LOPQLRVLRXSZPG-UHFFFAOYSA-N 0.000 description 1
- JHWMAMNRFYMRJV-UHFFFAOYSA-N 6-methoxy-4-(4-phenoxyanilino)-7-[2-(triazol-2-yl)ethoxy]quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCN3N=CC=N3)C(OC)=CC2=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 JHWMAMNRFYMRJV-UHFFFAOYSA-N 0.000 description 1
- ZEXRIKNMQBQAND-UHFFFAOYSA-N 6-methoxy-7-(3-morpholin-4-ylpropoxy)-4-[4-(triazol-2-ylmethyl)anilino]quinoline-3-carbonitrile Chemical compound N#CC1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC(C=C1)=CC=C1CN1N=CC=N1 ZEXRIKNMQBQAND-UHFFFAOYSA-N 0.000 description 1
- PZIXIFBGEDRCAM-UHFFFAOYSA-N 6-nitro-4-oxo-1h-quinoline-3-carbonitrile Chemical compound N1C=C(C#N)C(=O)C2=CC([N+](=O)[O-])=CC=C21 PZIXIFBGEDRCAM-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- ADNGABPKOSWJBG-UHFFFAOYSA-N 7-(2-chloroethoxy)-N-(1H-indazol-6-yl)-6-methoxyquinolin-4-amine Chemical compound ClCCOC1=C(C=C2C(=CC=NC2=C1)NC1=CC=C2C=NNC2=C1)OC ADNGABPKOSWJBG-UHFFFAOYSA-N 0.000 description 1
- ZWQHQQHGQPCDRZ-UHFFFAOYSA-N 7-(2-methoxyethoxy)quinoline-3-carbonitrile Chemical compound COCCOC1=CC=C2C=C(C=NC2=C1)C#N ZWQHQQHGQPCDRZ-UHFFFAOYSA-N 0.000 description 1
- PGQKUPUNLKDETF-UHFFFAOYSA-N 7-[2-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCN(CC1)CCC21OCCO2 PGQKUPUNLKDETF-UHFFFAOYSA-N 0.000 description 1
- PPWXQAXRPNYXEP-UHFFFAOYSA-N 7-[2-(2-hydroxyethylamino)ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OCCNCCO)OC)=C1 PPWXQAXRPNYXEP-UHFFFAOYSA-N 0.000 description 1
- DUFOXOFHCHAHQF-UHFFFAOYSA-N 7-[2-(3,4-dihydro-1h-isoquinolin-2-yl)ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1CC2=CC=CC=C2CN1CCOC1=CC2=NC=C(C#N)C(NC=3C=C4NN=CC4=CC=3)=C2C=C1OC DUFOXOFHCHAHQF-UHFFFAOYSA-N 0.000 description 1
- XCWAWTVTINOSBS-UHFFFAOYSA-N 7-[2-(4-hydroxypiperidin-1-yl)ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound COC1=CC2=C(NC=3C=C4NN=CC4=CC=3)C(C#N)=CN=C2C=C1OCCN1CCC(O)CC1 XCWAWTVTINOSBS-UHFFFAOYSA-N 0.000 description 1
- NAVKQEILHSWRJB-UHFFFAOYSA-N 7-[2-(dimethylamino)ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OCCN(C)C)OC)=C1 NAVKQEILHSWRJB-UHFFFAOYSA-N 0.000 description 1
- LFSLSWYMEMDYTK-UHFFFAOYSA-N 7-[2-[bis(2-hydroxyethyl)amino]ethoxy]-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC2=C3C=C(C(=CC3=NC=C2C#N)OCCN(CCO)CCO)OC)=C1 LFSLSWYMEMDYTK-UHFFFAOYSA-N 0.000 description 1
- MJXYFLJHTUSJGU-UHFFFAOYSA-N 7-amino-4-methyl-1h-quinolin-2-one Chemical compound NC1=CC=C2C(C)=CC(=O)NC2=C1 MJXYFLJHTUSJGU-UHFFFAOYSA-N 0.000 description 1
- UWYRRKURMGDFSI-UHFFFAOYSA-N 7-ethoxy-4-(1h-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C(C#N)=CN=C3C=C(C(=CC3=2)OC)OCC)=C1 UWYRRKURMGDFSI-UHFFFAOYSA-N 0.000 description 1
- NGWOZKQCIQCFCV-UHFFFAOYSA-N 7-hydroxy-4-(1H-indazol-6-ylamino)quinoline-3-carbonitrile Chemical compound C1=C2C=NNC2=CC(NC=2C3=CC=C(C=C3N=CC=2C#N)O)=C1 NGWOZKQCIQCFCV-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
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- DQHYXZIUHJKCOB-UHFFFAOYSA-N 9-oxo-3,6-dihydro-2h-[1,4]dioxino[2,3-g]quinoline-8-carbonitrile Chemical compound O1CCOC2=C1C=C1NC=C(C#N)C(=O)C1=C2 DQHYXZIUHJKCOB-UHFFFAOYSA-N 0.000 description 1
- WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- UZYBGCMAMGZGEJ-UHFFFAOYSA-N CC(COC1=CC(C(C=C1OC)C(=O)OC)(N)[N+](=O)[O-])Cl Chemical compound CC(COC1=CC(C(C=C1OC)C(=O)OC)(N)[N+](=O)[O-])Cl UZYBGCMAMGZGEJ-UHFFFAOYSA-N 0.000 description 1
- RKFMDDMFUHVCTD-UHFFFAOYSA-N CC1=C(C(=C(C(=O)O)C=C1)N=CN(C)C)OC Chemical compound CC1=C(C(=C(C(=O)O)C=C1)N=CN(C)C)OC RKFMDDMFUHVCTD-UHFFFAOYSA-N 0.000 description 1
- AJDAYVOWVGORDO-UHFFFAOYSA-N CC1=CC(=O)NC2=C1C=CC(=C2)NC3=NC4=CC=CC=C4C=C3C#N Chemical compound CC1=CC(=O)NC2=C1C=CC(=C2)NC3=NC4=CC=CC=C4C=C3C#N AJDAYVOWVGORDO-UHFFFAOYSA-N 0.000 description 1
- LSDOSXYYOREBQR-UHFFFAOYSA-N CCOC1=CC2=CC(=C(N=C2C=C1OCC)NC3=CC4=C(C=C3)C=CN4)C#N Chemical compound CCOC1=CC2=CC(=C(N=C2C=C1OCC)NC3=CC4=C(C=C3)C=CN4)C#N LSDOSXYYOREBQR-UHFFFAOYSA-N 0.000 description 1
- SAGUKJOPHPTQKT-UHFFFAOYSA-N COC(C1=C(C(=C(C=C1)OC)OCCCN1CCOCC1)[N+](=O)[O-])=O Chemical compound COC(C1=C(C(=C(C=C1)OC)OCCCN1CCOCC1)[N+](=O)[O-])=O SAGUKJOPHPTQKT-UHFFFAOYSA-N 0.000 description 1
- RGSPAIJCDMASLT-UHFFFAOYSA-N COC(C1=C(C(=CC(=C1)OC)OCCCl)[N+](=O)[O-])=O Chemical compound COC(C1=C(C(=CC(=C1)OC)OCCCl)[N+](=O)[O-])=O RGSPAIJCDMASLT-UHFFFAOYSA-N 0.000 description 1
- JVIFWLUZWHWHLC-UHFFFAOYSA-N COC1=C(C(=C2C(=C1)C(=C(C=N2)C#N)NC3=CC=CC4=NNN=C43)OC)OC Chemical compound COC1=C(C(=C2C(=C1)C(=C(C=N2)C#N)NC3=CC=CC4=NNN=C43)OC)OC JVIFWLUZWHWHLC-UHFFFAOYSA-N 0.000 description 1
- AHUZEXNDMVKWJH-UHFFFAOYSA-N COC1=C(C=C2C(=C1)C(=C(C=N2)C#N)NC3=CC4=C(C=C3)C=NN4)OCCNCC5OCCO5 Chemical compound COC1=C(C=C2C(=C1)C(=C(C=N2)C#N)NC3=CC4=C(C=C3)C=NN4)OCCNCC5OCCO5 AHUZEXNDMVKWJH-UHFFFAOYSA-N 0.000 description 1
- UZUDLGPGVUKCCG-UHFFFAOYSA-N COC1=C(C=C2C(=C1)C(=C(C=N2)C#N)NC3=CC4=NNN=C4C=C3)OC Chemical compound COC1=C(C=C2C(=C1)C(=C(C=N2)C#N)NC3=CC4=NNN=C4C=C3)OC UZUDLGPGVUKCCG-UHFFFAOYSA-N 0.000 description 1
- QPBFSYSGAVEEOG-UHFFFAOYSA-N COC1=CC2=C(C=CN=C2C=C1OC)NC3=CC=CC4=C3C=CN4 Chemical compound COC1=CC2=C(C=CN=C2C=C1OC)NC3=CC=CC4=C3C=CN4 QPBFSYSGAVEEOG-UHFFFAOYSA-N 0.000 description 1
- HAXOGPHFNUWDMJ-UHFFFAOYSA-N COC1=CC2=CC(=C(N=C2C=C1OC)NC3=C(C=CC4=CC=CC=C43)O)C#N Chemical compound COC1=CC2=CC(=C(N=C2C=C1OC)NC3=C(C=CC4=CC=CC=C43)O)C#N HAXOGPHFNUWDMJ-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- CKJLKRLSTOTOLF-UHFFFAOYSA-N Cl.N1=CC(=CC2=CC=CC=C12)C#N Chemical compound Cl.N1=CC(=CC2=CC=CC=C12)C#N CKJLKRLSTOTOLF-UHFFFAOYSA-N 0.000 description 1
- 241000501308 Conus spectrum Species 0.000 description 1
- 239000012625 DNA intercalator Substances 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- 101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
- 101000938346 Homo sapiens Ephrin type-A receptor 2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 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
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- PGHHNEOXUPHUMX-UHFFFAOYSA-N N#CC1=CC(C=C(C(OC2)=C3)OC2NC2=CC=C(C=NN4)C4=C2)=C3N=C1 Chemical compound N#CC1=CC(C=C(C(OC2)=C3)OC2NC2=CC=C(C=NN4)C4=C2)=C3N=C1 PGHHNEOXUPHUMX-UHFFFAOYSA-N 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
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-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
- 102000043276 Oncogene Human genes 0.000 description 1
- 108010074118 Oncogene Proteins v-erbB Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 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
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 240000008042 Zea mays Species 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
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 125000005122 aminoalkylamino group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- HDFRDWFLWVCOGP-UHFFFAOYSA-N carbonothioic O,S-acid Chemical class OC(S)=O HDFRDWFLWVCOGP-UHFFFAOYSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000032677 cell aging Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 201000000159 corneal neovascularization Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000012649 demethylating agent Substances 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000017338 epidermoid cysts Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- VPIRXVBLQOIGLC-UHFFFAOYSA-N ethyl 2-(dimethylaminomethylideneamino)-4,5-diethoxybenzoate Chemical compound CCOC(=O)C1=CC(OCC)=C(OCC)C=C1N=CN(C)C VPIRXVBLQOIGLC-UHFFFAOYSA-N 0.000 description 1
- YZOWMIHUDJVXBH-UHFFFAOYSA-N ethyl 2-amino-4,5-bis(2-methoxyethoxy)benzoate Chemical compound CCOC(=O)C1=CC(OCCOC)=C(OCCOC)C=C1N YZOWMIHUDJVXBH-UHFFFAOYSA-N 0.000 description 1
- KTMGNAIGXYODKQ-UHFFFAOYSA-N ethyl 2-cyano-3-ethoxyprop-2-enoate Chemical compound CCOC=C(C#N)C(=O)OCC KTMGNAIGXYODKQ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- HNHHBKDPQPDTMD-UHFFFAOYSA-N furan thiophene Chemical compound O1C=CC=C1.O1C=CC=C1.S1C=CC=C1.S1C=CC=C1 HNHHBKDPQPDTMD-UHFFFAOYSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000007946 glucose deprivation Effects 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 102000050156 human MAP2K1 Human genes 0.000 description 1
- 102000045373 human MAPK1 Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 229940006487 lithium cation Drugs 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- USSRZSRGYKCCEK-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)-3,6-dimethoxybenzoate Chemical compound COC(=O)C1=C(OC)C=CC(OC)=C1N=CN(C)C USSRZSRGYKCCEK-UHFFFAOYSA-N 0.000 description 1
- ZVKQLOCFMSUXFU-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=CC(OC)=C1N=CN(C)C ZVKQLOCFMSUXFU-UHFFFAOYSA-N 0.000 description 1
- ADKJMUQRPSFDAR-UHFFFAOYSA-N methyl 2-(dimethylaminomethylideneamino)-4,5-diethoxybenzoate Chemical compound CCOC1=CC(N=CN(C)C)=C(C(=O)OC)C=C1OCC ADKJMUQRPSFDAR-UHFFFAOYSA-N 0.000 description 1
- WYHBJUPMCJWBDD-UHFFFAOYSA-N methyl 2-amino-4,5-diethoxybenzoate Chemical compound CCOC1=CC(N)=C(C(=O)OC)C=C1OCC WYHBJUPMCJWBDD-UHFFFAOYSA-N 0.000 description 1
- MWAMTEYWDWYKQO-UHFFFAOYSA-N methyl 2-amino-4-(3-chloropropoxy)-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=C(OCCCCl)C=C1N MWAMTEYWDWYKQO-UHFFFAOYSA-N 0.000 description 1
- CKHQUPXMMAOBTC-UHFFFAOYSA-N methyl 2-amino-5-methoxy-4-phenylmethoxybenzoate Chemical compound C1=C(N)C(C(=O)OC)=CC(OC)=C1OCC1=CC=CC=C1 CKHQUPXMMAOBTC-UHFFFAOYSA-N 0.000 description 1
- LUWJKZQXEIOILK-UHFFFAOYSA-N methyl 4-methoxy-5-(3-morpholin-4-ylpropoxy)-2-nitrobenzoate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OC)=CC(OCCCN2CCOCC2)=C1OC LUWJKZQXEIOILK-UHFFFAOYSA-N 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- HNFCLQLANGSACZ-UHFFFAOYSA-N n,n-bis(2-methoxyethyl)prop-2-yn-1-amine Chemical compound COCCN(CC#C)CCOC HNFCLQLANGSACZ-UHFFFAOYSA-N 0.000 description 1
- VTLAOFNWLFSDLF-UHFFFAOYSA-N n,n-bis(2-methoxyethyl)propan-2-amine Chemical compound COCCN(C(C)C)CCOC VTLAOFNWLFSDLF-UHFFFAOYSA-N 0.000 description 1
- ILBIXZPOMJFOJP-UHFFFAOYSA-N n,n-dimethylprop-2-yn-1-amine Chemical compound CN(C)CC#C ILBIXZPOMJFOJP-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- WMMWXOZETAUBKF-UHFFFAOYSA-N n-[4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-3-cyanoquinolin-6-yl]prop-2-enamide Chemical compound CN1C=CN=C1SC(C(=C1)Cl)=CC=C1NC1=C(C#N)C=NC2=CC=C(NC(=O)C=C)C=C12 WMMWXOZETAUBKF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- NRTUTGBOQZQBMB-UHFFFAOYSA-N n-phenylquinolin-4-amine Chemical class C=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 NRTUTGBOQZQBMB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 208000014081 polyp of colon Diseases 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000034918 positive regulation of cell growth Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000012256 powdered iron Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- LJZPPWWHKPGCHS-UHFFFAOYSA-N propargyl chloride Chemical compound ClCC#C LJZPPWWHKPGCHS-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000000722 protumoral effect Effects 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- BEJXOECDIXUTLN-UHFFFAOYSA-N pyrido[2,3-c]pyridazine Chemical compound N1=NC=CC2=CC=CN=C21 BEJXOECDIXUTLN-UHFFFAOYSA-N 0.000 description 1
- OHZYAOYVLLHTGW-UHFFFAOYSA-N pyrido[3,2-c]pyridazine Chemical compound C1=CN=NC2=CC=CN=C21 OHZYAOYVLLHTGW-UHFFFAOYSA-N 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 1
- RJSRSRITMWVIQT-UHFFFAOYSA-N quinolin-6-amine Chemical compound N1=CC=CC2=CC(N)=CC=C21 RJSRSRITMWVIQT-UHFFFAOYSA-N 0.000 description 1
- BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical class C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000003345 scintillation counting Methods 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
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 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 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 150000003557 thiazoles Chemical group 0.000 description 1
- XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 108010002164 tyrosine receptor Proteins 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16280298A | 1998-09-29 | 1998-09-29 | |
PCT/US1999/022054 WO2000018761A1 (en) | 1998-09-29 | 1999-09-22 | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
SK4132001A3 SK4132001A3 (en) | 2002-01-07 |
SK284846B6 true SK284846B6 (sk) | 2005-12-01 |
Family
ID=22587189
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK413-2001A SK284846B6 (sk) | 1998-09-29 | 1999-09-22 | Deriváty substituovaného 3-kyanochinolínu, spôsob ich prípravy, ich použitie a farmaceutický prostriedok s ich obsahom |
Country Status (25)
Country | Link |
---|---|
EP (1) | EP1117659B1 (cs) |
JP (1) | JP4548642B2 (cs) |
KR (1) | KR100705142B1 (cs) |
CN (1) | CN1165532C (cs) |
AR (1) | AR035155A1 (cs) |
AT (1) | ATE255575T1 (cs) |
AU (1) | AU763669B2 (cs) |
BR (1) | BR9914167B1 (cs) |
CA (1) | CA2344169C (cs) |
CZ (1) | CZ303899B6 (cs) |
DE (1) | DE69913364T2 (cs) |
DK (1) | DK1117659T3 (cs) |
EA (1) | EA004436B1 (cs) |
ES (1) | ES2211175T3 (cs) |
HU (1) | HUP0103520A3 (cs) |
IL (2) | IL142121A0 (cs) |
NO (1) | NO324563B1 (cs) |
NZ (1) | NZ510551A (cs) |
PL (1) | PL201475B1 (cs) |
PT (1) | PT1117659E (cs) |
SK (1) | SK284846B6 (cs) |
TW (1) | TWI233437B (cs) |
UA (1) | UA72749C2 (cs) |
WO (1) | WO2000018761A1 (cs) |
ZA (1) | ZA200102729B (cs) |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6811779B2 (en) | 1994-02-10 | 2004-11-02 | Imclone Systems Incorporated | Methods for reducing tumor growth with VEGF receptor antibody combined with radiation and chemotherapy |
GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
UA71971C2 (en) | 1999-06-04 | 2005-01-17 | Agoron Pharmaceuticals Inc | Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases |
US7141581B2 (en) | 1999-07-02 | 2006-11-28 | Agouron Pharmaceuticals, Inc. | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
AR035851A1 (es) * | 2000-03-28 | 2004-07-21 | Wyeth Corp | 3-cianoquinolinas, 3-ciano-1,6-naftiridinas y 3-ciano-1,7-naftiridinas como inhibidoras de proteina quinasas |
US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
MXPA02010222A (es) | 2000-04-18 | 2003-05-23 | Agouron Pharma | Pirazoles para inhibir proteina cinasa. |
EP1313726A1 (en) | 2000-08-09 | 2003-05-28 | AstraZeneca AB | Quinoline derivatives having vegf inhibiting activity |
US6576644B2 (en) * | 2000-09-06 | 2003-06-10 | Bristol-Myers Squibb Co. | Quinoline inhibitors of cGMP phosphodiesterase |
AU2001295791A1 (en) | 2000-11-02 | 2002-05-15 | Astrazeneca Ab | 4-substituted quinolines as antitumor agents |
EP1337524A1 (en) | 2000-11-02 | 2003-08-27 | AstraZeneca AB | Substituted quinolines as antitumor agents |
AUPR213700A0 (en) | 2000-12-18 | 2001-01-25 | Biota Scientific Management Pty Ltd | Antiviral agents |
ES2312557T3 (es) | 2001-04-19 | 2009-03-01 | Astrazeneca Ab | Derivados de quinazolina. |
EP1412367A4 (en) | 2001-06-21 | 2006-05-03 | Ariad Pharma Inc | NEW CHINOLINE AND ITS USE |
DE60215178T2 (de) | 2001-07-16 | 2007-08-23 | Astrazeneca Ab | Quinolin-derivate und ihre verwendung als inhibitoren der tyrosine kinase |
WO2003030909A1 (en) * | 2001-09-25 | 2003-04-17 | Bayer Pharmaceuticals Corporation | 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer |
WO2003050090A1 (en) * | 2001-11-27 | 2003-06-19 | Wyeth Holdings Corporation | 3-cyanoquinolines as inhibitors of egf-r and her2 kinases |
WO2003047585A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Pharmaceutical compositions comprising benzofuranyl substituted 3-cyanoquinoline derivatives and their use for the treatment of solid tumours |
AU2002365664A1 (en) * | 2001-12-05 | 2003-06-17 | Astrazeneca Ab | Quinoline derivatives as antitumour agents |
GB0129099D0 (en) * | 2001-12-05 | 2002-01-23 | Astrazeneca Ab | Chemical compounds |
WO2003047584A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives |
WO2003047583A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Pharmaceutical compositions comprising benzofuranyl substituted 3-cyanoquinoline derivatives and their use for the treatment of solid tumours |
US8367824B2 (en) * | 2002-01-28 | 2013-02-05 | Ube Industries Ltd. | Process for producing quinazolin-4-one derivative |
ATE429230T1 (de) | 2002-07-09 | 2009-05-15 | Astrazeneca Ab | Chinazoline derivative und ihre anwendung in der krebsbehandlung |
GB0215823D0 (en) * | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
CA2492911A1 (en) * | 2002-07-19 | 2004-01-29 | Memory Pharmaceuticals Corporation | 6-amino-1h-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors |
GB0225579D0 (en) | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
KR101089462B1 (ko) | 2002-11-04 | 2011-12-07 | 아스트라제네카 아베 | Src 티로신 키나제 억제제로서의 퀴나졸린 유도체 |
US7153889B2 (en) | 2002-11-12 | 2006-12-26 | Abbott Laboratories | Bicyclic-substituted amines as histamine-3 receptor ligands |
TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
EP1638600A4 (en) | 2003-06-09 | 2008-06-11 | Samuel Waksal | PROCESS FOR INHIBITING RECEPTOR TYROSINE KINASES WITH AN EXTRACELLULAR ANTAGONIST AND AN INTRA CELLULAR ANTAGONIST |
US7399865B2 (en) * | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
ATE520403T1 (de) | 2003-09-26 | 2011-09-15 | Exelixis Inc | N-ä3-fluoro-4-(ä6-(methyloxy)-7-ä(3-morpholin-4 ylpropyl)oxyüquinolin-4-ylüoxy)phenylü-n'-(4- fluorophenyl)cyclopropane-1,1-dicarboxamid zur behandlung von krebs |
US7781591B2 (en) | 2006-06-13 | 2010-08-24 | Wyeth Llc | Substituted 3-cyanopyridines as protein kinase inhibitors |
SG151288A1 (en) * | 2003-12-18 | 2009-04-30 | Janssen Pharmaceutica Nv | 3-cyano-quinoline derivatives with antiproliferative activity |
NZ547794A (en) | 2003-12-18 | 2009-11-27 | Janssen Pharmaceutica Nv | Pyrido- and pyrimidopyrimidine derivatives as anti-proliferative agents |
AU2004309166B2 (en) * | 2003-12-23 | 2008-02-21 | Pfizer Inc. | Novel quinoline derivatives |
US7626030B2 (en) | 2004-01-23 | 2009-12-01 | Amgen Inc. | Compounds and methods of use |
AU2005224267B2 (en) | 2004-03-19 | 2011-07-21 | Imclone Llc | Human anti-epidermal growth factor receptor antibody |
NZ588139A (en) | 2004-04-08 | 2012-02-24 | Targegen Inc | 7-Aryl-3-arylamino-benzo[1,2,4]triazine derivatives |
NI200700147A (es) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina inhibidores de cinasas dirigidos a multip |
EP1848414B1 (en) | 2005-02-03 | 2011-04-06 | The General Hospital Corporation | Method for treating gefitinib resistant cancer |
EP1883631A1 (en) * | 2005-05-25 | 2008-02-06 | Wyeth | Methods of synthesizing substituted 3-cyanoquinolines and intermediates thereof |
EP2100614B8 (en) | 2005-06-17 | 2013-11-20 | ImClone LLC | Antibody against PDGFR-alpha for use in the treatment of tumours |
CN101228130A (zh) | 2005-07-27 | 2008-07-23 | 弗·哈夫曼-拉罗切有限公司 | 芳氧基喹啉和其作为5-ht6的用途 |
WO2007017740A1 (en) | 2005-08-08 | 2007-02-15 | Pfizer Inc. | Salts and polymorphs of a vergf-r inhibitor |
WO2007025044A2 (en) | 2005-08-24 | 2007-03-01 | Bristol-Myers Squibb Company | Biomarkers and methods for determining sensitivity to epidermal growth factor receptor modulators |
LT1951684T (lt) | 2005-11-01 | 2016-11-10 | Targegen, Inc. | Kinazės bi-aril-meta-pirimidino slopikliai |
JP2009514870A (ja) | 2005-11-04 | 2009-04-09 | ワイス | mTORインヒビター、ハーセプチン、および/またはHKI−272の抗悪性腫瘍性組み合わせ |
CA2649146A1 (en) * | 2006-04-14 | 2007-10-25 | Astrazeneca Ab | 4-anilinoquinoline-3-carboxamides as csf-1r kinase inhibitors |
PE20080336A1 (es) * | 2006-06-13 | 2008-06-03 | Wyeth Corp | 3-cianopiridinas sustituidas como inhibidoras de la proteina quinasa |
ES2569428T3 (es) | 2006-07-13 | 2016-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina como MTKI |
DK2170827T3 (da) * | 2007-06-21 | 2013-11-18 | Janssen Pharmaceutica Nv | Indolin-2-oner og aza-indolin-2-oner |
TWI459947B (zh) * | 2007-06-26 | 2014-11-11 | Otsuka Pharma Co Ltd | 苯并氮呯化合物及藥學製劑 |
JP5536647B2 (ja) | 2007-07-27 | 2014-07-02 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ピロロピリミジン |
CN101148439B (zh) * | 2007-09-14 | 2011-06-22 | 东南大学 | 一种吉非替尼的制备方法 |
US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
RU2492860C2 (ru) | 2008-06-17 | 2013-09-20 | УАЙТ ЭлЭлСи | Антиопластические комбинации, содержащие нкi-272 и винорелбин |
BRPI0916694B1 (pt) | 2008-08-04 | 2021-06-08 | Wyeth Llc | uso de neratinibe em combinação com capecitabina para tratar câncer de mama metastático de erbb-2 positivo, kit e produto compreendendo os mesmos |
CN106083714B (zh) | 2009-01-16 | 2019-11-26 | 埃克塞里艾克西斯公司 | N-(4-{[6,7-双(甲基氧基)喹啉-4-基]氧基}苯基)-n′-(4-氟苯基)环丙烷-1,1-二甲酰胺苹果酸盐及其结晶型 |
ES2941894T3 (es) | 2009-04-06 | 2023-05-26 | Wyeth Llc | Régimen de tratamiento que utiliza neratinib contra el cáncer de mama |
UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
CN102020639A (zh) | 2009-09-14 | 2011-04-20 | 上海恒瑞医药有限公司 | 6-氨基喹唑啉或3-氰基喹啉类衍生物、其制备方法及其在医药上的应用 |
WO2011053779A2 (en) | 2009-10-30 | 2011-05-05 | Bristol-Myers Squibb Company | Methods for treating cancer in patients having igf-1r inhibitor resistance |
GB0922302D0 (en) * | 2009-12-22 | 2010-02-03 | Imp Innovations Ltd | Compounds |
WO2011153942A1 (zh) * | 2010-06-09 | 2011-12-15 | 天津和美生物技术有限公司 | 氰基喹啉衍生物 |
CN102958919A (zh) * | 2010-07-02 | 2013-03-06 | 霍夫曼-拉罗奇有限公司 | 新的四氢喹啉衍生物 |
CA2816957A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
GB201106870D0 (en) | 2011-04-26 | 2011-06-01 | Univ Belfast | Marker |
EP2766497A1 (en) | 2011-10-13 | 2014-08-20 | Bristol-Myers Squibb Company | Methods for selecting and treating cancer in patients with igf-1r/ir inhibitors |
TW201412740A (zh) * | 2012-09-20 | 2014-04-01 | Bayer Pharma AG | 經取代之吡咯并嘧啶胺基苯并噻唑酮 |
JP6669499B2 (ja) | 2013-02-15 | 2020-03-18 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物 |
JP2016510000A (ja) | 2013-02-20 | 2016-04-04 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物およびその使用 |
US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
CA2928658A1 (en) | 2013-11-01 | 2015-05-07 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
US9636340B2 (en) | 2013-11-12 | 2017-05-02 | Ayyappan K. Rajasekaran | Kinase inhibitors |
JP6553632B2 (ja) | 2013-11-18 | 2019-07-31 | フォーマ セラピューティクス,インコーポレイテッド | Betブロモドメイン阻害剤としてのテトラヒドロキノリン組成物 |
US9422281B2 (en) | 2013-11-18 | 2016-08-23 | Forma Therapeutics, Inc. | Benzopiperazine compositions as BET bromodomain inhibitors |
JP6631616B2 (ja) | 2014-07-26 | 2020-01-15 | ノース・アンド・サウス・ブラザー・ファーマシー・インベストメント・カンパニー・リミテッド | CDK阻害剤としての2−アミノ−ピリド[2,3−d]ピリミジン−7(8H)−オン誘導体及びその使用 |
MX2019002629A (es) | 2016-09-08 | 2019-10-07 | Kala Pharmaceuticals Inc | Formas cristalinas de compuestos terapéuticos y usos de los mismos. |
EP3509423A4 (en) | 2016-09-08 | 2020-05-13 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
WO2018078143A1 (en) | 2016-10-28 | 2018-05-03 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Means and methods for determining efficacy of anti-egfr inhibitors in colorectal cancer (crc) therapy |
AU2018289864B2 (en) * | 2017-06-23 | 2022-03-31 | Cstone Pharmaceuticals | Coumarin-like cyclic compound as MEK inhibitor and use thereof |
AU2019255310B2 (en) | 2018-04-18 | 2022-11-24 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
CA3100977A1 (en) | 2018-05-21 | 2019-11-28 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
WO2021105117A1 (en) | 2019-11-28 | 2021-06-03 | Bayer Aktiengesellschaft | Substituted aminoquinolones as dgkalpha inhibitors for immune activation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
-
1999
- 1999-09-22 AT AT99948410T patent/ATE255575T1/de active
- 1999-09-22 WO PCT/US1999/022054 patent/WO2000018761A1/en not_active Application Discontinuation
- 1999-09-22 SK SK413-2001A patent/SK284846B6/sk not_active IP Right Cessation
- 1999-09-22 CA CA2344169A patent/CA2344169C/en not_active Expired - Lifetime
- 1999-09-22 KR KR1020017003892A patent/KR100705142B1/ko not_active Expired - Lifetime
- 1999-09-22 DE DE69913364T patent/DE69913364T2/de not_active Expired - Lifetime
- 1999-09-22 JP JP2000572221A patent/JP4548642B2/ja not_active Expired - Lifetime
- 1999-09-22 ES ES99948410T patent/ES2211175T3/es not_active Expired - Lifetime
- 1999-09-22 CZ CZ20011038A patent/CZ303899B6/cs not_active IP Right Cessation
- 1999-09-22 AU AU61593/99A patent/AU763669B2/en not_active Expired
- 1999-09-22 DK DK99948410T patent/DK1117659T3/da active
- 1999-09-22 BR BRPI9914167-1A patent/BR9914167B1/pt not_active IP Right Cessation
- 1999-09-22 EA EA200100411A patent/EA004436B1/ru not_active IP Right Cessation
- 1999-09-22 UA UA2001042929A patent/UA72749C2/uk unknown
- 1999-09-22 NZ NZ510551A patent/NZ510551A/xx not_active IP Right Cessation
- 1999-09-22 PL PL346934A patent/PL201475B1/pl unknown
- 1999-09-22 EP EP99948410A patent/EP1117659B1/en not_active Expired - Lifetime
- 1999-09-22 IL IL14212199A patent/IL142121A0/xx active IP Right Grant
- 1999-09-22 PT PT99948410T patent/PT1117659E/pt unknown
- 1999-09-22 HU HU0103520A patent/HUP0103520A3/hu unknown
- 1999-09-22 CN CNB998113697A patent/CN1165532C/zh not_active Expired - Lifetime
- 1999-09-28 AR ARP990104884A patent/AR035155A1/es active IP Right Grant
- 1999-09-29 TW TW088116630A patent/TWI233437B/zh not_active IP Right Cessation
-
2001
- 2001-03-20 IL IL142121A patent/IL142121A/en not_active IP Right Cessation
- 2001-03-28 NO NO20011575A patent/NO324563B1/no not_active IP Right Cessation
- 2001-04-03 ZA ZA200102729A patent/ZA200102729B/en unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SK284846B6 (sk) | Deriváty substituovaného 3-kyanochinolínu, spôsob ich prípravy, ich použitie a farmaceutický prostriedok s ich obsahom | |
US6288082B1 (en) | Substituted 3-cyanoquinolines | |
KR100736502B1 (ko) | 단백질 티로신 키나제 억제제로서 치환된 3-시아노퀴놀린 | |
US6002008A (en) | Substituted 3-cyano quinolines | |
US6297258B1 (en) | Substituted 3-cyanoquinolines | |
PL196471B1 (pl) | Podstawione 3-cyjanochinoliny, sposoby ich otrzymywania, kompozycja farmaceutyczna oraz zastosowanie tych związków w leczeniu | |
JP2003528880A (ja) | 三環系タンパクキナーゼ阻害薬 | |
BRPI9917841B1 (pt) | compostos 3-ciano quinolina substituídos e composições compreendendo os mesmos | |
HU230095B1 (hu) | Protein tirozin kinázokat gátló hatású szubsztituált 3-cianokinolinok | |
AU2012209038B2 (en) | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors | |
HK1035188B (en) | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors | |
MXPA01003230A (en) | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors | |
AU2010227057A1 (en) | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK4A | Expiry of patent |
Expiry date: 20190922 |