CA1074801A - 5,8-disubstituted quinolic derivatives and processes for preparing same - Google Patents
5,8-disubstituted quinolic derivatives and processes for preparing sameInfo
- Publication number
- CA1074801A CA1074801A CA268,691A CA268691A CA1074801A CA 1074801 A CA1074801 A CA 1074801A CA 268691 A CA268691 A CA 268691A CA 1074801 A CA1074801 A CA 1074801A
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbostyril
- hydroxy
- carbon atoms
- isopropylaminobutyl
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 112
- 230000008569 process Effects 0.000 title claims abstract description 77
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims abstract description 231
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 48
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
- 125000002252 acyl group Chemical group 0.000 claims abstract description 30
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 20
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 13
- 230000036961 partial effect Effects 0.000 claims abstract description 8
- -1 3,4-dihydrocarbostyril compound Chemical class 0.000 claims description 138
- 125000004432 carbon atom Chemical group C* 0.000 claims description 79
- 238000005917 acylation reaction Methods 0.000 claims description 58
- 230000010933 acylation Effects 0.000 claims description 56
- 239000000126 substance Substances 0.000 claims description 38
- 239000002904 solvent Substances 0.000 claims description 35
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical class C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 claims description 18
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 14
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 claims description 14
- FKNXQNWAXFXVNW-UHFFFAOYSA-N 8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]-1H-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC FKNXQNWAXFXVNW-UHFFFAOYSA-N 0.000 claims description 13
- 229910052783 alkali metal Inorganic materials 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 9
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- 150000001339 alkali metal compounds Chemical class 0.000 claims description 7
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 150000007514 bases Chemical class 0.000 claims description 5
- LJWGDDVMRSFGJD-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] cyclohexanecarboxylate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(NC(C)C)CC)=CC=C1OC(=O)C1CCCCC1 LJWGDDVMRSFGJD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 4
- 150000003512 tertiary amines Chemical class 0.000 claims description 4
- LABGHXARDKOAFS-UHFFFAOYSA-N 5-[2-(ethylamino)-1-hydroxybutyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(CC)NCC LABGHXARDKOAFS-UHFFFAOYSA-N 0.000 claims description 3
- 239000007868 Raney catalyst Substances 0.000 claims description 3
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
- NMSYPNVBVJNZER-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 4-methylbenzoate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(NC(C)C)CC)=CC=C1OC(=O)C1=CC=C(C)C=C1 NMSYPNVBVJNZER-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- DAUAQNGYDSHRET-UHFFFAOYSA-N 3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OC DAUAQNGYDSHRET-UHFFFAOYSA-N 0.000 claims description 2
- GVLJOWZTPWDMRI-UHFFFAOYSA-N 5-[1-hydroxy-2-(propan-2-ylamino)butyl]-8-(2-methylphenoxy)-1H-quinolin-2-one Chemical compound C1(=C(C=CC=C1)OC=1C=CC(=C2C=CC(NC=12)=O)C(C(CC)NC(C)C)O)C GVLJOWZTPWDMRI-UHFFFAOYSA-N 0.000 claims description 2
- GPVDHNVGGIAOQT-UHFFFAOYSA-N Veratric acid Natural products COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- QVKSJODVQXGNCG-UHFFFAOYSA-N 8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC QVKSJODVQXGNCG-UHFFFAOYSA-N 0.000 claims 2
- LZEKCCBZLJONDH-UHFFFAOYSA-N [5-[1-(4-methylbenzoyl)oxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 4-methylbenzoate Chemical compound C=1C=C(OC(=O)C=2C=CC(C)=CC=2)C=2NC(=O)C=CC=2C=1C(C(NC(C)C)CC)OC(=O)C1=CC=C(C)C=C1 LZEKCCBZLJONDH-UHFFFAOYSA-N 0.000 claims 2
- RODWHOVOSCQMON-UHFFFAOYSA-N [5-[1-(4-methylbenzoyl)oxy-2-(propan-2-ylamino)butyl]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] 4-methylbenzoate Chemical compound C=1C=C(OC(=O)C=2C=CC(C)=CC=2)C=2NC(=O)CCC=2C=1C(C(NC(C)C)CC)OC(=O)C1=CC=C(C)C=C1 RODWHOVOSCQMON-UHFFFAOYSA-N 0.000 claims 2
- JRBCWKGEOSAKPH-UHFFFAOYSA-N [5-[1-(cyclohexanecarbonyloxy)-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] cyclohexanecarboxylate Chemical compound C=1C=C(OC(=O)C2CCCCC2)C=2NC(=O)C=CC=2C=1C(C(NC(C)C)CC)OC(=O)C1CCCCC1 JRBCWKGEOSAKPH-UHFFFAOYSA-N 0.000 claims 2
- DVFUTVMGMCEOSR-UHFFFAOYSA-N [5-[1-(cyclopropanecarbonyloxy)-2-[2-(3,4-dimethoxyphenyl)ethylamino]ethyl]-2-oxo-1h-quinolin-8-yl] cyclopropanecarboxylate Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC(C=1C=2C=CC(=O)NC=2C(OC(=O)C2CC2)=CC=1)OC(=O)C1CC1 DVFUTVMGMCEOSR-UHFFFAOYSA-N 0.000 claims 2
- GMISJJZNMHXRGJ-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 2-phenylacetate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(NC(C)C)CC)=CC=C1OC(=O)CC1=CC=CC=C1 GMISJJZNMHXRGJ-UHFFFAOYSA-N 0.000 claims 2
- GEGAZBZDHWUJFO-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 3,3-dimethylbutanoate Chemical compound N1C(=O)C=CC2=C1C(OC(=O)CC(C)(C)C)=CC=C2C(O)C(NC(C)C)CC GEGAZBZDHWUJFO-UHFFFAOYSA-N 0.000 claims 2
- CTOMHALZIVQAJZ-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] 4-methylbenzoate Chemical compound C1=2NC(=O)CCC=2C(C(O)C(NC(C)C)CC)=CC=C1OC(=O)C1=CC=C(C)C=C1 CTOMHALZIVQAJZ-UHFFFAOYSA-N 0.000 claims 2
- JEDQHIYBQUOGIC-UHFFFAOYSA-N [5-[2-(ethylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] acetate Chemical compound N1C(=O)C=CC2=C1C(OC(C)=O)=CC=C2C(O)C(CC)NCC JEDQHIYBQUOGIC-UHFFFAOYSA-N 0.000 claims 2
- MNBGZYVKZLCVTG-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxypropyl]-2-oxo-1h-quinolin-8-yl] 1,3-benzodioxole-5-carboxylate Chemical compound N1C(=O)C=CC2=C1C(OC(=O)C=1C=C3OCOC3=CC=1)=CC=C2C(O)C(NC(C)(C)C)C MNBGZYVKZLCVTG-UHFFFAOYSA-N 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- XCPZBBPCQMUMJT-UHFFFAOYSA-N 5-[2-(tert-butylamino)-1-hydroxypropyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(NC(C)(C)C)C XCPZBBPCQMUMJT-UHFFFAOYSA-N 0.000 claims 1
- RMIBSUZSLDJMTB-UHFFFAOYSA-N [5-[1-(2-methylpropanoyloxy)-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 2-methylpropanoate Chemical compound N1C(=O)C=CC2=C1C(OC(=O)C(C)C)=CC=C2C(OC(=O)C(C)C)C(NC(C)C)CC RMIBSUZSLDJMTB-UHFFFAOYSA-N 0.000 claims 1
- RFCWHHDEPHQZQT-UHFFFAOYSA-N [5-[1-acetyloxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] acetate Chemical compound N1C(=O)C=CC2=C1C(OC(C)=O)=CC=C2C(OC(C)=O)C(NC(C)C)CC RFCWHHDEPHQZQT-UHFFFAOYSA-N 0.000 claims 1
- UVKJBJNPNUZBHN-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 2-methylpropanoate Chemical compound N1C(=O)C=CC2=C1C(OC(=O)C(C)C)=CC=C2C(O)C(NC(C)C)CC UVKJBJNPNUZBHN-UHFFFAOYSA-N 0.000 claims 1
- LWKGXCTURLNKHA-UHFFFAOYSA-N [5-[1-hydroxy-2-(propan-2-ylamino)butyl]-2-oxo-1h-quinolin-8-yl] 3,4-dimethoxybenzoate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(NC(C)C)CC)=CC=C1OC(=O)C1=CC=C(OC)C(OC)=C1 LWKGXCTURLNKHA-UHFFFAOYSA-N 0.000 claims 1
- RFBAZSUSYKDODV-UHFFFAOYSA-N [5-[2-(benzylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] 4-chlorobenzoate Chemical compound C=1C=C(OC(=O)C=2C=CC(Cl)=CC=2)C=2NC(=O)C=CC=2C=1C(O)C(CC)NCC1=CC=CC=C1 RFBAZSUSYKDODV-UHFFFAOYSA-N 0.000 claims 1
- QXHJFTBRFUMPME-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxypropyl]-2-oxo-1h-quinolin-8-yl] 2-methylpropanoate Chemical compound C1=CC(=O)NC2=C1C(C(O)C(C)NC(C)(C)C)=CC=C2OC(=O)C(C)C QXHJFTBRFUMPME-UHFFFAOYSA-N 0.000 claims 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 6
- 230000004936 stimulating effect Effects 0.000 abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 4
- 125000005842 heteroatom Chemical group 0.000 abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 3
- 229940124630 bronchodilator Drugs 0.000 abstract description 2
- 239000000168 bronchodilator agent Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 239000002220 antihypertensive agent Substances 0.000 abstract 1
- 229940030600 antihypertensive agent Drugs 0.000 abstract 1
- 239000000810 peripheral vasodilating agent Substances 0.000 abstract 1
- 229960002116 peripheral vasodilator Drugs 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 165
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- 239000000203 mixture Substances 0.000 description 74
- 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 34
- 238000002844 melting Methods 0.000 description 34
- 230000008018 melting Effects 0.000 description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- 238000001816 cooling Methods 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 18
- 239000005457 ice water Substances 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000013078 crystal Substances 0.000 description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- ZUGRYLJRHKHZLR-UHFFFAOYSA-N 1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)C=CC2=C1 ZUGRYLJRHKHZLR-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 238000010531 catalytic reduction reaction Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000004820 halides Chemical class 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 4
- 208000009079 Bronchial Spasm Diseases 0.000 description 4
- 208000014181 Bronchial disease Diseases 0.000 description 4
- 206010006482 Bronchospasm Diseases 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
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- MGCLHZDVTDYGPY-UHFFFAOYSA-N [5-[2-(ethylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] 3-cyclohexylbutanoate;hydrochloride Chemical compound Cl.C1=2NC(=O)C=CC=2C(C(O)C(CC)NCC)=CC=C1OC(=O)CC(C)C1CCCCC1 MGCLHZDVTDYGPY-UHFFFAOYSA-N 0.000 description 1
- BDPLIGRPCFVHRG-UHFFFAOYSA-N [5-[2-(ethylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] acetate;hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(OC(C)=O)=CC=C2C(O)C(CC)NCC BDPLIGRPCFVHRG-UHFFFAOYSA-N 0.000 description 1
- WASXHUAQTYDPHS-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxypropyl]-2-oxo-1h-quinolin-8-yl] 2-methylpropanoate;hydrochloride Chemical compound Cl.C1=CC(=O)NC2=C1C(C(O)C(C)NC(C)(C)C)=CC=C2OC(=O)C(C)C WASXHUAQTYDPHS-UHFFFAOYSA-N 0.000 description 1
- DAJIQDKKKWCOBH-UHFFFAOYSA-N [8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]quinolin-2-yl] 2-methylpropanoate;hydrochloride Chemical compound Cl.CC(C)C(=O)OC1=CC=C2C(C(O)C(NC(C)C)CC)=CC=C(O)C2=N1 DAJIQDKKKWCOBH-UHFFFAOYSA-N 0.000 description 1
- JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000004479 aerosol dispenser Substances 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
- 125000006640 cycloheptyl carbonyl group Chemical group 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- XTLNYNMNUCLWEZ-UHFFFAOYSA-N ethanol;propan-2-one Chemical compound CCO.CC(C)=O XTLNYNMNUCLWEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940081330 tena Drugs 0.000 description 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 description 1
- 229960002312 tolazoline Drugs 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
- C07D215/32—Esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51121423A JPS609713B2 (ja) | 1976-10-08 | 1976-10-08 | カルボスチリル誘導体 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1074801A true CA1074801A (en) | 1980-04-01 |
Family
ID=14810767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA268,691A Expired CA1074801A (en) | 1976-10-08 | 1976-12-23 | 5,8-disubstituted quinolic derivatives and processes for preparing same |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4223137A (en, 2012) |
| JP (1) | JPS609713B2 (en, 2012) |
| BE (1) | BE849794A (en, 2012) |
| CA (1) | CA1074801A (en, 2012) |
| CH (1) | CH618431A5 (en, 2012) |
| DE (1) | DE2658544C2 (en, 2012) |
| FR (1) | FR2378521A1 (en, 2012) |
| GB (1) | GB1540628A (en, 2012) |
| NL (1) | NL174041C (en, 2012) |
| SE (1) | SE434395B (en, 2012) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH17194A (en) * | 1980-03-06 | 1984-06-19 | Otsuka Pharma Co Ltd | Novel carbostyril derivatives,and pharmaceutical composition containing the same |
| US4322425A (en) * | 1980-03-14 | 1982-03-30 | Otsuka Pharmaceutical Co., Ltd. | Compositions for treating glaucoma |
| FI77852C (fi) * | 1981-02-17 | 1989-05-10 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av nya, saosom hjaertmediciner anvaendbara substituerade amid- och (maettad heterocykel)karbonylkarbostyrilderivat. |
| US4456757A (en) * | 1981-03-20 | 1984-06-26 | Asahi Kasei Kogyo Kabushiki Kaisha | Isoquinolinesulfonyl derivatives and process for the preparation thereof |
| ATE27451T1 (de) * | 1981-03-24 | 1987-06-15 | Ciba Geigy Ag | Acyl-chinolinonderivate, verfahren zu ihrer herstellung, diese enthaltende pharmazeutische praeparate und ihre verwendung. |
| GB8334494D0 (en) * | 1983-12-24 | 1984-02-01 | Tanabe Seiyaku Co | Carbostyril derivatives |
| JPS60173736U (ja) * | 1984-04-25 | 1985-11-18 | 株式会社昭和製作所 | 緩衝器用サブタンク |
| JPS61191767A (ja) * | 1985-02-20 | 1986-08-26 | 辻本 夘太郎 | 植物張り家屋 |
| JPS62113672A (ja) * | 1985-11-12 | 1987-05-25 | 本田技研工業株式会社 | リヤクツシヨン用リザ−ブタンク |
| JPS6348401U (en, 2012) * | 1986-09-17 | 1988-04-01 | ||
| JPS63106132A (ja) * | 1986-10-24 | 1988-05-11 | Mazda Motor Corp | 車両のサスペンシヨン装置 |
| US4687776A (en) * | 1986-10-24 | 1987-08-18 | Warner-Lambert Company | Drug stabilization |
| JPS6374545U (en, 2012) * | 1986-10-31 | 1988-05-18 | ||
| JPS6417047U (en, 2012) * | 1987-07-21 | 1989-01-27 | ||
| US4894219A (en) * | 1988-03-29 | 1990-01-16 | University Of Florida | Beta-agonist carbostyril derivatives, assay method and pharmacological composition |
| JPH026831U (en, 2012) * | 1988-06-28 | 1990-01-17 | ||
| US6653323B2 (en) | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US20030229058A1 (en) | 2001-11-13 | 2003-12-11 | Moran Edmund J. | Aryl aniline beta2 adrenergic receptor agonists |
| JP2005527618A (ja) | 2002-05-28 | 2005-09-15 | セラヴァンス インコーポレーテッド | アルコキシアリールβ２アドレナリン作動性レセプターアゴニスト |
| MXPA05005661A (es) * | 2002-11-27 | 2005-11-23 | Artesian Therapeutics Inc | Compuestos con actividad antagonista o antagonista parcial mixta inhibidora de fosfodiesterasa y beta-adrenergica para el tratamiento de insuficiencia cardiaca. |
| TW200526547A (en) | 2003-09-22 | 2005-08-16 | Theravance Inc | Amino-substituted ethylamino β2 adrenergic receptor agonists |
| TW200531692A (en) | 2004-01-12 | 2005-10-01 | Theravance Inc | Aryl aniline derivatives as β2 adrenergic receptor agonists |
| FR2869893B1 (fr) * | 2004-05-06 | 2006-07-28 | Rhodia Chimie Sa | Nouveaux granules de phosphates de calcium de type hydroxyapatite, leur procede de preparation et leurs applications |
| US7307076B2 (en) | 2004-05-13 | 2007-12-11 | Boehringer Ingelheim International Gmbh | Beta agonists for the treatment of respiratory diseases |
| WO2005110990A1 (de) * | 2004-05-13 | 2005-11-24 | Boehringer Ingelheim International Gmbh | Hydroxy-substituierte benzkondensierte heterozyklen als betaagonisten zur behandlung von atemwegserkrankungen |
| CN1984876A (zh) | 2004-06-03 | 2007-06-20 | 施万制药 | 二胺类β2肾上腺素能受体激动剂 |
| JP2008512470A (ja) | 2004-09-10 | 2008-04-24 | セラヴァンス， インコーポレーテッド | アミジン置換アリールアニリン化合物 |
| GB0624757D0 (en) * | 2006-12-12 | 2007-01-17 | Sosei R & D Ltd | Novel compounds |
| US9090618B2 (en) | 2012-12-27 | 2015-07-28 | Purdue Pharma L.P. | Substituted benzimidazole-type piperidine compounds and uses thereof |
| WO2014108449A1 (en) | 2013-01-08 | 2014-07-17 | Atrogi Ab | A screening method, a kit, a method of treatment and a compound for use in a method of treatment |
| GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714740D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
| GB201903832D0 (en) | 2019-03-20 | 2019-05-01 | Atrogi Ab | New compounds and methods |
| GB202205895D0 (en) | 2022-04-22 | 2022-06-08 | Atrogi Ab | New medical uses |
| WO2024153813A1 (en) | 2023-01-20 | 2024-07-25 | Atrogi Ab | Beta 2-adrenergic receptor agonists for treatment or prevention of muscle wasting |
| GB202302225D0 (en) | 2023-02-16 | 2023-04-05 | Atrogi Ab | New medical uses |
| GB202303229D0 (en) | 2023-03-06 | 2023-04-19 | Atrogi Ab | New medical uses |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3975391A (en) * | 1973-12-26 | 1976-08-17 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]ethyl-8-hydroxy-3,4-dihydrocarbostyril derivatives |
| JPS539227B2 (en, 2012) * | 1973-12-26 | 1978-04-04 | ||
| US4022784A (en) * | 1974-01-31 | 1977-05-10 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-substituted-carbostyril and -3,4-dihydrocarbostyril derivatives |
| US4026897A (en) * | 1974-01-31 | 1977-05-31 | Otsuka Pharmaceutical Company | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxycarbostyril derivatives |
| US3994901A (en) * | 1974-06-13 | 1976-11-30 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxy-3,4-dihydrocarbostyril derivatives |
| FI58329C (fi) * | 1974-11-08 | 1981-01-12 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av i 8-staellning substituerade 5-(3'-alkylamino-2'-hydroxi)propoxi-3,4-dihydrokarbostyrilderivat |
-
1976
- 1976-10-08 JP JP51121423A patent/JPS609713B2/ja not_active Expired
- 1976-12-23 GB GB53966/76A patent/GB1540628A/en not_active Expired
- 1976-12-23 DE DE2658544A patent/DE2658544C2/de not_active Expired
- 1976-12-23 BE BE173581A patent/BE849794A/xx not_active IP Right Cessation
- 1976-12-23 SE SE7614539A patent/SE434395B/xx not_active IP Right Cessation
- 1976-12-23 CA CA268,691A patent/CA1074801A/en not_active Expired
- 1976-12-23 FR FR7638918A patent/FR2378521A1/fr active Granted
- 1976-12-23 NL NLAANVRAGE7614329,A patent/NL174041C/xx not_active IP Right Cessation
- 1976-12-27 CH CH1634376A patent/CH618431A5/fr not_active IP Right Cessation
-
1978
- 1978-08-10 US US05/932,572 patent/US4223137A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS609713B2 (ja) | 1985-03-12 |
| AU2085576A (en) | 1978-04-06 |
| NL174041C (nl) | 1984-04-16 |
| FR2378521B1 (en, 2012) | 1979-06-29 |
| NL7614329A (nl) | 1978-04-11 |
| DE2658544C2 (de) | 1985-10-03 |
| SE434395B (sv) | 1984-07-23 |
| CH618431A5 (en, 2012) | 1980-07-31 |
| BE849794A (fr) | 1977-04-15 |
| JPS5346983A (en) | 1978-04-27 |
| GB1540628A (en) | 1979-02-14 |
| FR2378521A1 (fr) | 1978-08-25 |
| DE2658544A1 (de) | 1978-04-13 |
| NL174041B (nl) | 1983-11-16 |
| US4223137A (en) | 1980-09-16 |
| SE7614539L (sv) | 1978-04-09 |
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