CA2026890C - Quinoline derivatives, their production and use - Google Patents
Quinoline derivatives, their production and use Download PDFInfo
- Publication number
- CA2026890C CA2026890C CA002026890A CA2026890A CA2026890C CA 2026890 C CA2026890 C CA 2026890C CA 002026890 A CA002026890 A CA 002026890A CA 2026890 A CA2026890 A CA 2026890A CA 2026890 C CA2026890 C CA 2026890C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- dihydro
- oxo
- methyl
- chlorophenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 title description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 claims abstract description 20
- 108010054082 Sterol O-acyltransferase Proteins 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 117
- 238000000034 method Methods 0.000 claims description 57
- -1 nitro, carboxyl Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 150000003248 quinolines Chemical class 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 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 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- WQNFGLDAHVQQGC-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-1,6,7-trimethyl-2-oxoquinolin-3-yl]-3-(2,4-difluorophenyl)urea Chemical compound C=1C=C(F)C=C(F)C=1NC(=O)NC=1C(=O)N(C)C=2C=C(C)C(C)=CC=2C=1C1=CC=CC=C1Cl WQNFGLDAHVQQGC-UHFFFAOYSA-N 0.000 claims description 2
- PIQDFPRGBITFAB-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-1-ethyl-6,8-dimethyl-2-oxoquinolin-3-yl]-3-(2,4-difluorophenyl)urea Chemical compound C=1C=C(F)C=C(F)C=1NC(=O)NC=1C(=O)N(CC)C2=C(C)C=C(C)C=C2C=1C1=CC=CC=C1Cl PIQDFPRGBITFAB-UHFFFAOYSA-N 0.000 claims description 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 description 2
- UKUUTNHPWJKNQP-UHFFFAOYSA-N 1-[6-chloro-1-methyl-4-(2-methylphenyl)-2-oxoquinolin-3-yl]-3-(2-methyl-6-propan-2-ylphenyl)urea Chemical compound CC(C)C1=CC=CC(C)=C1NC(=O)NC(C(N(C)C1=CC=C(Cl)C=C11)=O)=C1C1=CC=CC=C1C UKUUTNHPWJKNQP-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- LUDZGPFTZCBLDT-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[1,6,7-trimethyl-4-(2-methylphenyl)-2-oxoquinolin-3-yl]urea Chemical compound C=1C=C(F)C=C(F)C=1NC(=O)NC=1C(=O)N(C)C=2C=C(C)C(C)=CC=2C=1C1=CC=CC=C1C LUDZGPFTZCBLDT-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 23
- 125000003545 alkoxy group Chemical group 0.000 abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 137
- 238000000921 elemental analysis Methods 0.000 description 76
- 239000000203 mixture Substances 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 33
- 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 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 239000002585 base Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 15
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-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
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 150000002170 ethers Chemical class 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 239000000047 product Substances 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 229960001701 chloroform Drugs 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
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 6
- 229960000443 hydrochloric acid Drugs 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 150000001840 cholesterol esters Chemical class 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000001540 azides Chemical class 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
- 239000004202 carbamide Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 4
- 235000011167 hydrochloric acid Nutrition 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
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 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
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- IEEHKTFVUIVORU-UHFFFAOYSA-N 2-methylpropanedioyl dichloride Chemical compound ClC(=O)C(C)C(Cl)=O IEEHKTFVUIVORU-UHFFFAOYSA-N 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
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 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
- 239000003513 alkali Substances 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000004945 aromatic hydrocarbons 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000012320 chlorinating reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- 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
- 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 3
- 238000001914 filtration Methods 0.000 description 3
- 125000005843 halogen group Chemical group 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
- 239000012442 inert solvent Substances 0.000 description 3
- 230000005764 inhibitory process Effects 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
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- ODFDDSSSXDWTDP-UHFFFAOYSA-N methyl 4-(2-chlorophenyl)-6,7-dimethyl-2-oxo-1h-quinoline-3-carboxylate Chemical compound C12=CC(C)=C(C)C=C2NC(=O)C(C(=O)OC)=C1C1=CC=CC=C1Cl ODFDDSSSXDWTDP-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- NMJWILRMCPEMLK-UHFFFAOYSA-N 3-amino-4-(2-chlorophenyl)-1,6,7-trimethylquinolin-2-one Chemical compound NC=1C(=O)N(C)C=2C=C(C)C(C)=CC=2C=1C1=CC=CC=C1Cl NMJWILRMCPEMLK-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
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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)
- Public Health (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)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Measurement Of Radiation (AREA)
- Holo Graphy (AREA)
- Detergent Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26278289 | 1989-10-06 | ||
| JP262782/1989 | 1989-10-06 | ||
| JP32229089 | 1989-12-11 | ||
| JP322290/1989 | 1989-12-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2026890A1 CA2026890A1 (en) | 1991-04-07 |
| CA2026890C true CA2026890C (en) | 2001-09-18 |
Family
ID=26545706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002026890A Expired - Fee Related CA2026890C (en) | 1989-10-06 | 1990-10-04 | Quinoline derivatives, their production and use |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5223513A (enExample) |
| EP (1) | EP0421456B1 (enExample) |
| KR (1) | KR910007883A (enExample) |
| CN (1) | CN1050715A (enExample) |
| AT (1) | ATE116301T1 (enExample) |
| AU (1) | AU629048B2 (enExample) |
| CA (1) | CA2026890C (enExample) |
| DE (1) | DE69015541T2 (enExample) |
| FI (1) | FI904915A7 (enExample) |
| HU (1) | HUT55364A (enExample) |
| IE (1) | IE903454A1 (enExample) |
| IL (1) | IL95839A (enExample) |
| NO (1) | NO904300L (enExample) |
| NZ (1) | NZ235582A (enExample) |
| PT (1) | PT95515A (enExample) |
| RU (1) | RU2001910C1 (enExample) |
| TW (1) | TW205037B (enExample) |
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 |
| AU1879792A (en) * | 1991-04-26 | 1992-12-21 | Pfizer Inc. | 4-aryl-3-(heteroarylureido)quinoline derivatives |
| ATE175196T1 (de) * | 1992-01-23 | 1999-01-15 | Pfizer | 4-phenyl-3-(heteroarylureido)-1,2-dihydro-2- oxochinolin derivate, als antihypercholesterolemische und antiatherosklerotische mittel |
| TW241258B (enExample) * | 1992-04-15 | 1995-02-21 | Takeda Pharm Industry Co Ltd | |
| RU94046149A (ru) * | 1992-05-28 | 1996-11-27 | Пфайзер Инк. (US) | Новые n-арил и n-гетероарил производные мочевины как ингибиторы ацил кофермента а:холестерин ацил трансферазы (асат) фармацевтическая композиция, способ ингибирования (асат) |
| DE69315920T2 (de) * | 1992-09-04 | 1998-06-10 | Takeda Chemical Industries Ltd | Kondensierte heterozyklische Verbindungen, deren Herstellung und Verwendung |
| 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 (enExample) * | 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 |
| JP2001513560A (ja) * | 1997-08-28 | 2001-09-04 | ブリストル−マイヤーズ スクイブ カンパニー | ４−アリール−３−アミノキノリン−２−オン誘導体カリウムチャンネル調節剤 |
| US6452008B2 (en) | 1998-02-25 | 2002-09-17 | Sumitomo Pharmaceuticals Company, Limited | Pyridone derivatives and process for preparing the same |
| WO1999043659A1 (en) | 1998-02-25 | 1999-09-02 | Sumitomo Pharmaceuticals Co., Ltd. | Pyridone derivatives and process for producing the same |
| JP2002531549A (ja) * | 1998-12-04 | 2002-09-24 | ブリストル−マイヤーズ スクイブ カンパニー | カリウムチャネル・モジュレーターとしての３−置換−４−アリールキノリン−２−オン誘導体 |
| HUP0301010A3 (en) * | 2000-02-02 | 2005-03-29 | Warner Lambert Co | Dual inhibitors of cholesteryl ester and wax ester synthesis for sebaceous gland disorders and pharmaceutical compositions containing them |
| EP1375487B1 (en) * | 2001-03-02 | 2011-08-24 | Sumitomo Chemical Company, Limited | Process for producing quinoline-3-carboxylic acid compounds |
| CA2445623A1 (en) * | 2001-04-30 | 2002-11-07 | Pfizer Products Inc. | Methods for preparing cetp inhibitors |
| CA2539760C (en) | 2003-09-23 | 2011-01-25 | Merck & Co., Inc. | Quinoline potassium channel inhibitors |
| SG11201401937YA (en) * | 2011-11-04 | 2014-05-29 | Hoffmann La Roche | New aryl-quinoline derivatives |
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 (enExample) * | 1970-04-04 | 1976-06-23 | Takeda Chemical Industries Ltd | |
| JPS555502B1 (enExample) * | 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 PT PT95515A patent/PT95515A/pt not_active Application Discontinuation
- 1990-10-04 CA CA002026890A patent/CA2026890C/en not_active Expired - Fee Related
- 1990-10-05 HU HU906360A patent/HUT55364A/hu unknown
- 1990-10-05 FI FI904915A patent/FI904915A7/fi not_active Application Discontinuation
- 1990-10-05 NZ NZ235582A patent/NZ235582A/en unknown
- 1990-10-05 RU SU904831426A patent/RU2001910C1/ru active
- 1990-10-05 DE DE69015541T patent/DE69015541T2/de not_active Expired - Fee Related
- 1990-10-05 AT AT90119128T patent/ATE116301T1/de not_active IP Right Cessation
- 1990-10-05 CN CN90108222A patent/CN1050715A/zh active Pending
- 1990-10-05 EP EP90119128A patent/EP0421456B1/en not_active Expired - Lifetime
- 1990-10-06 KR KR1019900015908A patent/KR910007883A/ko not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IL95839A (en) | 1995-03-15 |
| CN1050715A (zh) | 1991-04-17 |
| DE69015541D1 (de) | 1995-02-09 |
| HUT55364A (en) | 1991-05-28 |
| ATE116301T1 (de) | 1995-01-15 |
| HU906360D0 (en) | 1991-04-29 |
| DE69015541T2 (de) | 1995-06-01 |
| RU2001910C1 (ru) | 1993-10-30 |
| AU629048B2 (en) | 1992-09-24 |
| NO904300D0 (no) | 1990-10-03 |
| EP0421456B1 (en) | 1994-12-28 |
| CA2026890A1 (en) | 1991-04-07 |
| FI904915A7 (fi) | 1991-04-07 |
| NO904300L (no) | 1991-04-08 |
| IL95839A0 (en) | 1991-06-30 |
| US5223513A (en) | 1993-06-29 |
| EP0421456A3 (en) | 1991-05-29 |
| TW205037B (enExample) | 1993-05-01 |
| JPH03223254A (ja) | 1991-10-02 |
| NZ235582A (en) | 1992-03-26 |
| KR910007883A (ko) | 1991-05-30 |
| PT95515A (pt) | 1991-08-14 |
| IE903454A1 (en) | 1991-04-10 |
| FI904915A0 (fi) | 1990-10-05 |
| AU6370790A (en) | 1991-04-11 |
| EP0421456A2 (en) | 1991-04-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |