HUT55364A - Process for producing quinoline derivatives and pharmaceutical compositions comprising such compounds as active ingredient - Google Patents
Process for producing quinoline derivatives and pharmaceutical compositions comprising such compounds as active ingredient Download PDFInfo
- Publication number
- HUT55364A HUT55364A HU906360A HU636090A HUT55364A HU T55364 A HUT55364 A HU T55364A HU 906360 A HU906360 A HU 906360A HU 636090 A HU636090 A HU 636090A HU T55364 A HUT55364 A HU T55364A
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- dihydro
- oxo
- compound
- methyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 113
- 238000000034 method Methods 0.000 title claims description 55
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 239000004480 active ingredient Substances 0.000 title claims description 4
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title claims description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 claims abstract description 5
- 108010054082 Sterol O-acyltransferase Proteins 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
- 150000003248 quinolines Chemical class 0.000 claims description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- KLLHUZLXXQCZJL-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-(3,4-dimethoxyphenyl)-1,6-dimethyl-2-oxoquinolin-3-yl]urea Chemical compound C1=C(OC)C(OC)=CC=C1C(C1=CC(C)=CC=C1N(C)C1=O)=C1NC(=O)NC1=CC=C(F)C=C1F KLLHUZLXXQCZJL-UHFFFAOYSA-N 0.000 claims description 2
- HRFQAAGFTMHKCS-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-ethyl-1-methyl-2-oxoquinolin-3-yl]-3-(2,4-difluorophenyl)urea Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(CC)=CC=C2N(C)C(=O)C=1NC(=O)NC1=CC=C(F)C=C1F HRFQAAGFTMHKCS-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- IDISPJOVQBMRNV-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-ethyl-1-methyl-2-oxoquinolin-3-yl]-3-(2-methyl-6-propan-2-ylphenyl)urea Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(CC)=CC=C2N(C)C(=O)C=1NC(=O)NC1=C(C)C=CC=C1C(C)C IDISPJOVQBMRNV-UHFFFAOYSA-N 0.000 claims 1
- DJAPLZGEQLWUCV-UHFFFAOYSA-N 1-[7-chloro-1,6-dimethyl-4-(2-methylphenyl)-2-oxoquinolin-3-yl]-3-(2,4-difluorophenyl)urea Chemical compound CC1=CC=CC=C1C(C1=CC(C)=C(Cl)C=C1N(C)C1=O)=C1NC(=O)NC1=CC=C(F)C=C1F DJAPLZGEQLWUCV-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010029897 Obsessive thoughts Diseases 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 183
- 238000000921 elemental analysis Methods 0.000 description 74
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 59
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 39
- -1 methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyl Chemical group 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000002585 base Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- 239000002178 crystalline material Substances 0.000 description 9
- 150000002170 ethers Chemical class 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 3
- 229910001863 barium hydroxide Inorganic materials 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 150000001840 cholesterol esters Chemical class 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
- 238000004440 column chromatography Methods 0.000 description 3
- BOQDZPHCWCIRRY-UHFFFAOYSA-N ethyl 4-(3,4-dimethoxyphenyl)-6-methyl-2-oxo-1h-quinoline-3-carboxylate Chemical compound C12=CC(C)=CC=C2NC(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C(OC)=C1 BOQDZPHCWCIRRY-UHFFFAOYSA-N 0.000 description 3
- YLTPUGQKOOWPIB-UHFFFAOYSA-N ethyl 6-chloro-1-methyl-2-oxo-4-phenylquinoline-3-carboxylate Chemical compound C12=CC(Cl)=CC=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=CC=C1 YLTPUGQKOOWPIB-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- IEEHKTFVUIVORU-UHFFFAOYSA-N 2-methylpropanedioyl dichloride Chemical compound ClC(=O)C(C)C(Cl)=O IEEHKTFVUIVORU-UHFFFAOYSA-N 0.000 description 2
- WVCHIKCSPJPRLX-UHFFFAOYSA-N 4-(2-chlorophenyl)-1,6,7-trimethyl-2-oxoquinoline-3-carboxylic acid Chemical compound OC(=O)C=1C(=O)N(C)C=2C=C(C)C(C)=CC=2C=1C1=CC=CC=C1Cl WVCHIKCSPJPRLX-UHFFFAOYSA-N 0.000 description 2
- DYUJVGCEPFDDFC-UHFFFAOYSA-N 6-chloro-2-oxo-4-phenyl-1h-quinoline-3-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)O)=C1C1=CC=CC=C1 DYUJVGCEPFDDFC-UHFFFAOYSA-N 0.000 description 2
- HAMHNJRELYSNHU-UHFFFAOYSA-N 6-chloro-4-(2-chlorophenyl)-1-methyl-2-oxoquinoline-3-carboxylic acid Chemical compound OC(=O)C=1C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl HAMHNJRELYSNHU-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000005949 ethanesulfonyloxy group Chemical group 0.000 description 1
- OYJXTOVLKZDGFK-UHFFFAOYSA-N ethanol;2-propan-2-yloxypropane Chemical compound CCO.CC(C)OC(C)C OYJXTOVLKZDGFK-UHFFFAOYSA-N 0.000 description 1
- KPRKRRJKKCVDDE-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-1-methyl-2-oxo-6-propan-2-ylquinoline-3-carboxylate Chemical compound C12=CC(C(C)C)=CC=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=CC=C1Cl KPRKRRJKKCVDDE-UHFFFAOYSA-N 0.000 description 1
- GLUQXXOXABKJAJ-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-2-methoxy-6,8-dimethylquinoline-3-carboxylate Chemical compound CCOC(=O)C1=C(OC)N=C2C(C)=CC(C)=CC2=C1C1=CC=CC=C1Cl GLUQXXOXABKJAJ-UHFFFAOYSA-N 0.000 description 1
- OORDCPZWRJNLRZ-UHFFFAOYSA-N ethyl 4-(2-chlorophenyl)-6-ethyl-1-methyl-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(CC)=CC=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=CC=C1Cl OORDCPZWRJNLRZ-UHFFFAOYSA-N 0.000 description 1
- YNNAVLGZRMNKDA-UHFFFAOYSA-N ethyl 6-chloro-2-oxo-4-phenyl-1h-quinoline-3-carboxylate Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)OCC)=C1C1=CC=CC=C1 YNNAVLGZRMNKDA-UHFFFAOYSA-N 0.000 description 1
- SVCHBFMHCNGGLT-UHFFFAOYSA-N ethyl 6-chloro-4-(2-chlorophenyl)-1-methyl-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(Cl)=CC=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=CC=C1Cl SVCHBFMHCNGGLT-UHFFFAOYSA-N 0.000 description 1
- KGMXVSCDDAPHFJ-UHFFFAOYSA-N ethyl 6-chloro-4-(3,4-dimethoxyphenyl)-1-methyl-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(Cl)=CC=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C(OC)=C1 KGMXVSCDDAPHFJ-UHFFFAOYSA-N 0.000 description 1
- MZWJHZLLXJPENY-UHFFFAOYSA-N ethyl 6-chloro-4-(3,4-dimethoxyphenyl)-2-oxo-1h-quinoline-3-carboxylate Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)OCC)=C1C1=CC=C(OC)C(OC)=C1 MZWJHZLLXJPENY-UHFFFAOYSA-N 0.000 description 1
- SJDXOGLBKJRVRV-UHFFFAOYSA-N ethyl 7-chloro-1,6-dimethyl-4-(2-methylphenyl)-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(C)=C(Cl)C=C2N(C)C(=O)C(C(=O)OCC)=C1C1=CC=CC=C1C SJDXOGLBKJRVRV-UHFFFAOYSA-N 0.000 description 1
- FKYIDHXDDDLYGR-UHFFFAOYSA-N ethyl 7-chloro-2-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(Cl)C=C2NC(=O)C(C(=O)OCC)=CC2=C1 FKYIDHXDDDLYGR-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate group Chemical group [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- SDLYGCDHGGJYAL-UHFFFAOYSA-N methyl 4-(2-chlorophenyl)-1,6,7-trimethyl-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(C)=C(C)C=C2N(C)C(=O)C(C(=O)OC)=C1C1=CC=CC=C1Cl SDLYGCDHGGJYAL-UHFFFAOYSA-N 0.000 description 1
- WSYHBYIEEVPZKH-UHFFFAOYSA-N methyl 4-(2-chlorophenyl)-1,6,8-trimethyl-2-oxoquinoline-3-carboxylate Chemical compound C12=CC(C)=CC(C)=C2N(C)C(=O)C(C(=O)OC)=C1C1=CC=CC=C1Cl WSYHBYIEEVPZKH-UHFFFAOYSA-N 0.000 description 1
- IRZIHUCGSLAMDQ-UHFFFAOYSA-N methyl 4-(2-chlorophenyl)-1-ethyl-6,7-dimethyl-2-oxoquinoline-3-carboxylate Chemical compound COC(=O)C=1C(=O)N(CC)C2=CC(C)=C(C)C=C2C=1C1=CC=CC=C1Cl IRZIHUCGSLAMDQ-UHFFFAOYSA-N 0.000 description 1
- ZZVHVJNMLYBXFP-UHFFFAOYSA-N methyl 4-(2-chlorophenyl)-2,6,8-trimethylquinoline-3-carboxylate Chemical compound COC(=O)C1=C(C)N=C2C(C)=CC(C)=CC2=C1C1=CC=CC=C1Cl ZZVHVJNMLYBXFP-UHFFFAOYSA-N 0.000 description 1
- YHQBBABNRWKMFT-UHFFFAOYSA-N methyl 6-chloro-4-(2-chlorophenyl)-2-methoxyquinoline-3-carboxylate Chemical compound COC(=O)C1=C(OC)N=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl YHQBBABNRWKMFT-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- XDUHQPOXLUAVEE-BPMMELMSSA-N oleoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCC\C=C/CCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 XDUHQPOXLUAVEE-BPMMELMSSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
Classifications
-
- 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
-
- 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
- C07D215/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Detergent Compositions (AREA)
- Measurement Of Radiation (AREA)
- Holo Graphy (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26278289 | 1989-10-06 | ||
| JP32229089 | 1989-12-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HU906360D0 HU906360D0 (en) | 1991-04-29 |
| HUT55364A true HUT55364A (en) | 1991-05-28 |
Family
ID=26545706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU906360A HUT55364A (en) | 1989-10-06 | 1990-10-05 | Process for producing quinoline derivatives and pharmaceutical compositions comprising such compounds as active ingredient |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5223513A (en]) |
| EP (1) | EP0421456B1 (en]) |
| KR (1) | KR910007883A (en]) |
| CN (1) | CN1050715A (en]) |
| AT (1) | ATE116301T1 (en]) |
| AU (1) | AU629048B2 (en]) |
| CA (1) | CA2026890C (en]) |
| DE (1) | DE69015541T2 (en]) |
| FI (1) | FI904915A7 (en]) |
| HU (1) | HUT55364A (en]) |
| IE (1) | IE903454A1 (en]) |
| IL (1) | IL95839A (en]) |
| NO (1) | NO904300L (en]) |
| NZ (1) | NZ235582A (en]) |
| PT (1) | PT95515A (en]) |
| RU (1) | RU2001910C1 (en]) |
| TW (1) | TW205037B (en]) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03181465A (ja) * | 1989-12-11 | 1991-08-07 | Takeda Chem Ind Ltd | キノリン誘導体 |
| CA2108014A1 (en) * | 1991-04-26 | 1992-10-27 | Ernest S. Hamanaka | 4-aryl-3-(heteroarylureido)quinoline derivatives |
| ES2125325T3 (es) * | 1992-01-23 | 1999-03-01 | Pfizer | Derivados de 4-fenil-3-(heteroarilureido)-1,2-dihidro-2-oxoquinolina como agentes antihipercolesterolemicos y antiateroscleroticos. |
| TW241258B (en]) * | 1992-04-15 | 1995-02-21 | Takeda Pharm Industry Co Ltd | |
| WO1993024458A1 (en) * | 1992-05-28 | 1993-12-09 | Pfizer Inc. | New n-aryl and n-heteroarylurea derivatives as inhibitors of acyl coenzyme a:cholesterol acyl transferase (acat) |
| EP0585913B1 (en) * | 1992-09-04 | 1997-12-29 | Takeda Chemical Industries, Ltd. | Condensed heterocyclic compounds, their production and use |
| US5565472A (en) * | 1992-12-21 | 1996-10-15 | Pfizer Inc. | 4-aryl-3-(heteroarylureido)-1,2-dihydro-2-oxo-quinoline derivatives as antihypercholesterolemic and antiatherosclerotic agents |
| NZ264063A (en) * | 1993-08-13 | 1995-11-27 | Nihon Nohyaku Co Ltd | N-(2-phenylpyrid-3-yl)- and n-(4-phenylpyrimidin-5-yl)-n'-phenylurea derivatives and pharmaceutical compositions |
| TW263498B (en]) * | 1993-11-10 | 1995-11-21 | Takeda Pharm Industry Co Ltd | |
| US6133326A (en) | 1994-08-31 | 2000-10-17 | Pfizer Inc | Compositions and methods for decreasing sebum production |
| US5843957A (en) * | 1995-05-19 | 1998-12-01 | Sumitomo Pharmaceuticals Company, Ltd. | Naphthyridine derivatives |
| US5972961A (en) * | 1997-08-28 | 1999-10-26 | Bristol-Myers Squibb Company | 4-aryl-3-aminoquinoline-2-one derivatives as potassium channel modulators |
| EP1086948A4 (en) | 1998-02-25 | 2004-03-10 | Sumitomo Pharma | PYRIDONE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF |
| US6452008B2 (en) | 1998-02-25 | 2002-09-17 | Sumitomo Pharmaceuticals Company, Limited | Pyridone derivatives and process for preparing the same |
| WO2000034244A1 (en) * | 1998-12-04 | 2000-06-15 | Bristol-Myers Squibb Company | 3-substituted-4-arylquinolin-2-one derivatives as potassium channel modulators |
| EE200200429A (et) | 2000-02-02 | 2003-12-15 | Warner-Lambert Company | Kolesteroolestri ja vahaestri sünteesi duaalsed inhibiitorid rasunäärme häirete jaoks |
| WO2002070488A1 (fr) * | 2001-03-02 | 2002-09-12 | Sumika Fine Chemicals Co., Ltd. | Procede de production d'un compose d'acide quinoline-3-carboxylique |
| PL366584A1 (en) * | 2001-04-30 | 2005-02-07 | Pfizer Products Inc. | Compounds useful as intermediates |
| EP1667973B1 (en) * | 2003-09-23 | 2013-12-04 | Merck Sharp & Dohme Corp. | Quinoline potassium channel inhibitors |
| BR112014010644A2 (pt) | 2011-11-04 | 2017-04-25 | Hoffmann La Roche | novos derivados de aril-quinolina |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1216878B (de) * | 1963-04-02 | 1966-05-18 | Cassella Farbwerke Mainkur Ag | Verfahren zur Herstellung von coronargefaesserweiternden Derivaten des 7-Hydroxy-2-oxo-1, 2-dihydrochinolins |
| NO133758C (en]) * | 1970-04-04 | 1976-06-23 | Takeda Chemical Industries Ltd | |
| JPS555502B1 (en]) * | 1971-07-31 | 1980-02-07 | ||
| US4530931A (en) * | 1983-01-03 | 1985-07-23 | Usv Pharmaceutical Corp. | 8-Quinoline carbanilates for the inhibition of lipolysis |
| DE3586445T2 (de) * | 1984-06-26 | 1993-01-14 | Merck & Co Inc | Kondensierte benzo-laktam-verbindungen und deren pharmazeutische zusammensetzungen. |
| IE892088L (en) * | 1988-07-12 | 1990-01-12 | William Henry Deryk Morris | Quinoline derivatives, their production and use |
-
1990
- 1990-09-20 TW TW079107912A patent/TW205037B/zh active
- 1990-09-25 IE IE345490A patent/IE903454A1/en unknown
- 1990-09-25 US US07/587,795 patent/US5223513A/en not_active Expired - Fee Related
- 1990-09-28 AU AU63707/90A patent/AU629048B2/en not_active Ceased
- 1990-09-28 IL IL9583990A patent/IL95839A/en not_active IP Right Cessation
- 1990-10-03 NO NO90904300A patent/NO904300L/no unknown
- 1990-10-04 CA CA002026890A patent/CA2026890C/en not_active Expired - Fee Related
- 1990-10-04 PT PT95515A patent/PT95515A/pt not_active Application Discontinuation
- 1990-10-05 NZ NZ235582A patent/NZ235582A/en unknown
- 1990-10-05 FI FI904915A patent/FI904915A7/fi not_active Application Discontinuation
- 1990-10-05 HU HU906360A patent/HUT55364A/hu unknown
- 1990-10-05 EP EP90119128A patent/EP0421456B1/en not_active Expired - Lifetime
- 1990-10-05 CN CN90108222A patent/CN1050715A/zh active Pending
- 1990-10-05 DE DE69015541T patent/DE69015541T2/de not_active Expired - Fee Related
- 1990-10-05 RU SU904831426A patent/RU2001910C1/ru active
- 1990-10-05 AT AT90119128T patent/ATE116301T1/de not_active IP Right Cessation
- 1990-10-06 KR KR1019900015908A patent/KR910007883A/ko not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2001910C1 (ru) | 1993-10-30 |
| FI904915A0 (fi) | 1990-10-05 |
| CA2026890C (en) | 2001-09-18 |
| EP0421456A2 (en) | 1991-04-10 |
| KR910007883A (ko) | 1991-05-30 |
| DE69015541T2 (de) | 1995-06-01 |
| NO904300L (no) | 1991-04-08 |
| US5223513A (en) | 1993-06-29 |
| IL95839A (en) | 1995-03-15 |
| PT95515A (pt) | 1991-08-14 |
| CA2026890A1 (en) | 1991-04-07 |
| AU629048B2 (en) | 1992-09-24 |
| NZ235582A (en) | 1992-03-26 |
| EP0421456B1 (en) | 1994-12-28 |
| ATE116301T1 (de) | 1995-01-15 |
| IE903454A1 (en) | 1991-04-10 |
| NO904300D0 (no) | 1990-10-03 |
| AU6370790A (en) | 1991-04-11 |
| CN1050715A (zh) | 1991-04-17 |
| TW205037B (en]) | 1993-05-01 |
| IL95839A0 (en) | 1991-06-30 |
| DE69015541D1 (de) | 1995-02-09 |
| JPH03223254A (ja) | 1991-10-02 |
| FI904915A7 (fi) | 1991-04-07 |
| HU906360D0 (en) | 1991-04-29 |
| EP0421456A3 (en) | 1991-05-29 |
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