HU194832B - Process for producing phenyl-quinolone-carboxylic acids and pharmaceutical compositions containing them - Google Patents
Process for producing phenyl-quinolone-carboxylic acids and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- HU194832B HU194832B HU842824A HU282484A HU194832B HU 194832 B HU194832 B HU 194832B HU 842824 A HU842824 A HU 842824A HU 282484 A HU282484 A HU 282484A HU 194832 B HU194832 B HU 194832B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- hydrogen
- fluoro
- compound
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- LUYXVKNRFKSASY-UHFFFAOYSA-N 2-oxo-4-phenyl-1h-quinoline-3-carboxylic acid Chemical class C12=CC=CC=C2NC(=O)C(C(=O)O)=C1C1=CC=CC=C1 LUYXVKNRFKSASY-UHFFFAOYSA-N 0.000 title 1
- 239000011734 sodium Substances 0.000 claims abstract description 21
- 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 claims abstract description 20
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 20
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 98
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
- 239000002253 acid Substances 0.000 claims description 41
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 30
- -1 chloro, bromo, methyl Chemical group 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000001153 fluoro group Chemical group F* 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 229910052801 chlorine Chemical group 0.000 claims description 22
- 239000000460 chlorine Chemical group 0.000 claims description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 239000011541 reaction mixture Substances 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 229910052736 halogen Chemical group 0.000 claims description 10
- 238000010992 reflux Methods 0.000 claims description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 9
- 239000011707 mineral Substances 0.000 claims description 9
- 239000007858 starting material Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 238000009835 boiling Methods 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- 150000003568 thioethers Chemical class 0.000 claims description 3
- 150000003573 thiols Chemical class 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 31
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 15
- 239000003960 organic solvent Substances 0.000 claims 8
- 150000007530 organic bases Chemical class 0.000 claims 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims 5
- 150000007522 mineralic acids Chemical class 0.000 claims 4
- 238000007363 ring formation reaction Methods 0.000 claims 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 3
- 150000007529 inorganic bases Chemical class 0.000 claims 3
- 230000002140 halogenating effect Effects 0.000 claims 2
- 159000000001 potassium salts Chemical class 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- CBEBHNPCZSDEAB-UHFFFAOYSA-N 2-(4h-quinolin-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1C2=CC=CC=C2CC=C1 CBEBHNPCZSDEAB-UHFFFAOYSA-N 0.000 claims 1
- KPEKVOIJAXGWOI-UHFFFAOYSA-N 5-fluoro-3-methyl-2-(4-phenylphenyl)quinoline-4-carboxylic acid Chemical compound N1=C2C=CC=C(F)C2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1 KPEKVOIJAXGWOI-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 230000001085 cytostatic effect Effects 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 37
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- JIPUGCBCIYYRSB-UHFFFAOYSA-N 3-phenylquinoline-2-carboxylic acid Chemical class OC(=O)C1=NC2=CC=CC=C2C=C1C1=CC=CC=C1 JIPUGCBCIYYRSB-UHFFFAOYSA-N 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 159000000000 sodium salts Chemical class 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 230000012010 growth Effects 0.000 description 7
- 208000032839 leukemia Diseases 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 3
- 150000003248 quinolines Chemical class 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- AZTFYJYLDIQSAG-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(propan-2-ylamino)propan-1-one Chemical compound CC(C)NC(C)C(=O)C1=CC=C(Cl)C=C1 AZTFYJYLDIQSAG-UHFFFAOYSA-N 0.000 description 2
- YTRMTPPVNRALON-UHFFFAOYSA-N 2-phenyl-4-quinolinecarboxylic acid Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=CC=C1 YTRMTPPVNRALON-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000006153 Pfitzinger synthesis reaction Methods 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000000386 athletic effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- BNJMRELGMDUDDB-UHFFFAOYSA-N $l^{1}-sulfanylbenzene Chemical compound [S]C1=CC=CC=C1 BNJMRELGMDUDDB-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
- JMBGDQSXJHLFTO-UHFFFAOYSA-N 1-(4-phenylphenyl)propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1C1=CC=CC=C1 JMBGDQSXJHLFTO-UHFFFAOYSA-N 0.000 description 1
- KODLUXHSIZOKTG-UHFFFAOYSA-N 1-aminobutan-2-ol Chemical compound CCC(O)CN KODLUXHSIZOKTG-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 1
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- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
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- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
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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
- C07D401/04—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
-
- 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
- C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
- C07D215/52—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4 with aryl radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51631983A | 1983-07-22 | 1983-07-22 | |
| US60510484A | 1984-04-30 | 1984-04-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT35248A HUT35248A (en) | 1985-06-28 |
| HU194832B true HU194832B (en) | 1988-03-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU842824A HU194832B (en) | 1983-07-22 | 1984-07-20 | Process for producing phenyl-quinolone-carboxylic acids and pharmaceutical compositions containing them |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0133244B1 (en, 2012) |
| AU (1) | AU583793B2 (en, 2012) |
| CA (1) | CA1288436C (en, 2012) |
| DE (1) | DE3483704D1 (en, 2012) |
| DK (1) | DK358784A (en, 2012) |
| ES (1) | ES8507498A1 (en, 2012) |
| FI (1) | FI86987C (en, 2012) |
| GR (1) | GR82234B (en, 2012) |
| HK (1) | HK142395A (en, 2012) |
| HU (1) | HU194832B (en, 2012) |
| IE (1) | IE57627B1 (en, 2012) |
| IL (1) | IL72471A (en, 2012) |
| NO (1) | NO167510C (en, 2012) |
| NZ (1) | NZ208966A (en, 2012) |
| PT (1) | PT78960B (en, 2012) |
| SU (2) | SU1393314A3 (en, 2012) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889862A (en) * | 1986-08-28 | 1989-12-26 | E. I. Du Pont De Nemours And Company | Freeze-dried pharmaceutical compositions of phenylquinoline carboxylic acids |
| WO1989006227A1 (en) * | 1987-12-28 | 1989-07-13 | The Dow Chemical Company | Phenoxyphenoxypropionates, intermediates thereof and methods of preparation |
| US4861783A (en) * | 1988-04-26 | 1989-08-29 | E. I. Du Pont De Nemours And Company | 4-quinoline carboxylic acid derivatives useful for treating skin and muco-epithelial diseases |
| US4968702A (en) * | 1989-01-17 | 1990-11-06 | American Cyanamid Company | Substituted quinolinecarboxylic acids |
| US4918077A (en) * | 1989-01-25 | 1990-04-17 | E. I. Du Pont De Nemours & Co., Inc. | 3-phenyl-5,6-dihydrobenz(c)acridine-7-carboxylic acids and related compounds as cancer chemotherapeutic agents |
| DE3905339A1 (de) * | 1989-02-22 | 1990-09-06 | Basf Ag | Chinolin-4-carbonsaeurederivate und deren verwendung |
| US5393891A (en) * | 1993-06-08 | 1995-02-28 | The Du Pont Merck Pharmaceutical Company | Immunoassay reagents and methods for detecting brequinar and analogs |
| TW448160B (en) * | 1993-12-28 | 2001-08-01 | Merck & Co Inc | Novel dicyclohexylamine salt and process for the preparation of leukotriene antagonists |
| ATE493389T1 (de) * | 1997-05-28 | 2011-01-15 | Aventis Pharma Inc | Chinoxalin-derivate die den von blutplättchen abstammenden wachstumsfaktor und/oder p56lck- tyrosinkinase hemmen |
| DE69814012T2 (de) * | 1997-12-19 | 2004-04-01 | Eli Lilly And Co., Indianapolis | Hypoglykàmische imidazoline derivate |
| JPWO2004002484A1 (ja) * | 2002-06-26 | 2005-10-27 | 協和醗酵工業株式会社 | ホスホジエステラーゼ阻害剤 |
| TW201018662A (en) * | 2005-12-12 | 2010-05-16 | Astrazeneca Ab | Alkylsulphonamide quinolines |
| US8232310B2 (en) * | 2006-12-29 | 2012-07-31 | Georgetown University | Targeting of EWS-FLI1 as anti-tumor therapy |
| NZ700612A (en) | 2012-04-12 | 2016-09-30 | Univ Georgetown | Methods and compositions for treating ewings sarcoma family of tumors |
| EP3060207A4 (en) | 2013-10-24 | 2017-04-12 | Georgetown University | Methods and compositions for treating cancer |
| CN105916522A (zh) | 2013-11-22 | 2016-08-31 | 建新公司 | 用于治疗神经变性疾病的新方法 |
| US9604927B2 (en) | 2014-10-09 | 2017-03-28 | Oncternal Therapeutics, Inc. | Indolinone compounds and uses thereof |
| DK3436434T3 (da) | 2016-03-31 | 2020-09-21 | Oncternal Therapeutics Inc | Indolin-analoger og anvendelser deraf |
| SG11201811661TA (en) | 2016-07-29 | 2019-01-30 | Oncternal Therapeutics Inc | Uses of indolinone compounds |
| CN115361948A (zh) * | 2019-12-26 | 2022-11-18 | 俄亥俄州国家创新基金会 | 抑制二氢乳清酸脱氢酶的方法和组合物 |
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| BE502610A (en, 2012) * | 1950-04-18 | |||
| US2888346A (en) * | 1955-08-22 | 1959-05-26 | Gen Aniline & Film Corp | Ultra-violet absorbing compounds |
-
1984
- 1984-07-19 DE DE8484108523T patent/DE3483704D1/de not_active Expired - Lifetime
- 1984-07-19 EP EP84108523A patent/EP0133244B1/en not_active Expired - Lifetime
- 1984-07-19 CA CA000459263A patent/CA1288436C/en not_active Expired - Lifetime
- 1984-07-19 AU AU30852/84A patent/AU583793B2/en not_active Ceased
- 1984-07-20 PT PT78960A patent/PT78960B/pt not_active IP Right Cessation
- 1984-07-20 IL IL72471A patent/IL72471A/xx not_active IP Right Cessation
- 1984-07-20 DK DK358784A patent/DK358784A/da not_active Application Discontinuation
- 1984-07-20 HU HU842824A patent/HU194832B/hu not_active IP Right Cessation
- 1984-07-20 GR GR75386A patent/GR82234B/el unknown
- 1984-07-20 NO NO842969A patent/NO167510C/no unknown
- 1984-07-20 ES ES534509A patent/ES8507498A1/es not_active Expired
- 1984-07-20 SU SU843776940A patent/SU1393314A3/ru active
- 1984-07-20 IE IE1873/84A patent/IE57627B1/en not_active IP Right Cessation
- 1984-07-20 FI FI842928A patent/FI86987C/fi not_active IP Right Cessation
- 1984-07-20 NZ NZ208966A patent/NZ208966A/en unknown
-
1986
- 1986-01-06 SU SU864000869A patent/SU1452480A3/ru active
-
1995
- 1995-09-07 HK HK142395A patent/HK142395A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ES534509A0 (es) | 1985-09-01 |
| FI842928A0 (fi) | 1984-07-20 |
| DK358784A (da) | 1985-01-23 |
| IL72471A (en) | 1988-11-15 |
| AU3085284A (en) | 1985-01-24 |
| SU1393314A3 (ru) | 1988-04-30 |
| FI842928L (fi) | 1985-01-23 |
| FI86987C (fi) | 1992-11-10 |
| NO167510B (no) | 1991-08-05 |
| PT78960A (en) | 1984-08-01 |
| IL72471A0 (en) | 1984-11-30 |
| SU1452480A3 (ru) | 1989-01-15 |
| EP0133244A3 (en) | 1985-12-11 |
| CA1288436C (en) | 1991-09-03 |
| AU583793B2 (en) | 1989-05-11 |
| IE57627B1 (en) | 1993-02-10 |
| IE841873L (en) | 1985-01-22 |
| NO167510C (no) | 1991-11-13 |
| EP0133244B1 (en) | 1990-12-05 |
| GR82234B (en, 2012) | 1984-12-13 |
| HK142395A (en) | 1995-09-15 |
| NO842969L (no) | 1985-01-23 |
| NZ208966A (en) | 1986-12-05 |
| EP0133244A2 (en) | 1985-02-20 |
| DK358784D0 (da) | 1984-07-20 |
| HUT35248A (en) | 1985-06-28 |
| FI86987B (fi) | 1992-07-31 |
| DE3483704D1 (de) | 1991-01-17 |
| ES8507498A1 (es) | 1985-09-01 |
| PT78960B (en) | 1986-10-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HPC4 | Succession in title of patentee |
Owner name: THE DU PONT MERCK PHARMACEUTICAL CO., US |
|
| HMM4 | Cancellation of final prot. due to non-payment of fee |