CH618431A5 - - Google Patents
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- CH618431A5 CH618431A5 CH1634376A CH1634376A CH618431A5 CH 618431 A5 CH618431 A5 CH 618431A5 CH 1634376 A CH1634376 A CH 1634376A CH 1634376 A CH1634376 A CH 1634376A CH 618431 A5 CH618431 A5 CH 618431A5
- Authority
- CH
- Switzerland
- Prior art keywords
- group
- compound
- carbostyril
- formula
- hydroxy
- Prior art date
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- -1 carboxylic acid halide Chemical class 0.000 claims description 122
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 120
- 239000000203 mixture Substances 0.000 claims description 97
- 150000001875 compounds Chemical class 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 63
- 238000005917 acylation reaction Methods 0.000 claims description 62
- 230000010933 acylation Effects 0.000 claims description 60
- 239000002904 solvent Substances 0.000 claims description 40
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000002252 acyl group Chemical group 0.000 claims description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 150000004820 halides Chemical class 0.000 claims description 23
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 16
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 229910052783 alkali metal Inorganic materials 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 150000001339 alkali metal compounds Chemical class 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 230000036961 partial effect Effects 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 150000003512 tertiary amines Chemical class 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 150000007514 bases Chemical class 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
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 4
- 239000010931 gold Substances 0.000 claims description 4
- 229910052737 gold Inorganic materials 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 claims 1
- 241001331845 Equus asinus x caballus Species 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 150000003855 acyl compounds Chemical class 0.000 claims 1
- 229940125810 compound 20 Drugs 0.000 claims 1
- 125000006502 nitrobenzyl group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 176
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- 230000008018 melting Effects 0.000 description 37
- 238000002844 melting Methods 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 22
- 238000001816 cooling Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 238000000354 decomposition reaction Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 238000004040 coloring Methods 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 238000001953 recrystallisation 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
- 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 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
- 150000001412 amines Chemical class 0.000 description 6
- 229960001340 histamine Drugs 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000007858 starting material Substances 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
- 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 description 4
- 208000009079 Bronchial Spasm Diseases 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- AEQDBKHAAWUCMT-UHFFFAOYSA-N Procaterol hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC AEQDBKHAAWUCMT-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 4
- 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 4
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
- ZUGRYLJRHKHZLR-UHFFFAOYSA-N 1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1=CC=C2NC(=O)C=CC2=C1 ZUGRYLJRHKHZLR-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 239000000370 acceptor Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000012433 hydrogen halide Substances 0.000 description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229940039009 isoproterenol Drugs 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- PNSYMRDCZYWBOT-UHFFFAOYSA-N 5-[2-(ethylamino)-1-hydroxybutyl]-8-hydroxy-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2C(O)C(CC)NCC PNSYMRDCZYWBOT-UHFFFAOYSA-N 0.000 description 2
- GILPYCRARNWSFX-UHFFFAOYSA-N 8-hydroxy-5-[1-hydroxy-2-(propan-2-ylamino)butyl]-3,4-dihydro-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)CCC2=C1C(O)=CC=C2C(O)C(NC(C)C)CC GILPYCRARNWSFX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 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 description 2
- 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 description 2
- 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 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 125000002587 enol group Chemical group 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
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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
- JHCXUMGCEVKREK-UHFFFAOYSA-N [5-[2-(ethylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] 3-cyclohexylpropanoate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(CC)NCC)=CC=C1OC(=O)CCC1CCCCC1 JHCXUMGCEVKREK-UHFFFAOYSA-N 0.000 description 1
- QJEOCRNTDACSBU-UHFFFAOYSA-N [5-[2-(ethylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] 4-methylbenzoate;hydrochloride Chemical compound Cl.C1=2NC(=O)C=CC=2C(C(O)C(CC)NCC)=CC=C1OC(=O)C1=CC=C(C)C=C1 QJEOCRNTDACSBU-UHFFFAOYSA-N 0.000 description 1
- MAQNXLKVDCLEAA-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxybutyl]-2-oxo-1H-quinolin-3-yl] 2-(4-methylphenyl)acetate Chemical compound CC1=CC=C(C=C1)CC(=O)OC=1C(NC2=CC=CC(=C2C=1)C(C(CC)NC(C)(C)C)O)=O MAQNXLKVDCLEAA-UHFFFAOYSA-N 0.000 description 1
- DOQARXUNTMSUEY-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxybutyl]-2-oxo-1h-quinolin-8-yl] 4-chlorobenzoate Chemical compound C1=2NC(=O)C=CC=2C(C(O)C(NC(C)(C)C)CC)=CC=C1OC(=O)C1=CC=C(Cl)C=C1 DOQARXUNTMSUEY-UHFFFAOYSA-N 0.000 description 1
- ISEOXTCFXQAZRZ-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxyethyl]-2-oxo-1h-quinolin-8-yl] 2-propylbenzoate Chemical compound CCCC1=CC=CC=C1C(=O)OC1=CC=C(C(O)CNC(C)(C)C)C2=C1NC(=O)C=C2 ISEOXTCFXQAZRZ-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- KFVBWSDBIWOYBO-UHFFFAOYSA-N [5-[2-(tert-butylamino)-1-hydroxypropyl]-2-oxo-3,4-dihydro-1h-quinolin-8-yl] 4-(4-chlorophenyl)pentanoate Chemical compound C=1C=C(C(O)C(C)NC(C)(C)C)C=2CCC(=O)NC=2C=1OC(=O)CCC(C)C1=CC=C(Cl)C=C1 KFVBWSDBIWOYBO-UHFFFAOYSA-N 0.000 description 1
- FABNZUDGAQEHLI-UHFFFAOYSA-N [5-[4-[(1-hydroxy-2-phenylethyl)amino]butyl]-2-oxo-1H-quinolin-8-yl] cyclohexanecarboxylate Chemical compound C=1C=C(OC(=O)C2CCCCC2)C=2NC(=O)C=CC=2C=1CCCCNC(O)CC1=CC=CC=C1 FABNZUDGAQEHLI-UHFFFAOYSA-N 0.000 description 1
- MEOGQDRNYXEUTH-UHFFFAOYSA-N [5-[4-[(1-hydroxy-2-phenylethyl)amino]butyl]-2-oxo-3,4-dihydro-1H-quinolin-8-yl] hexanoate Chemical compound C1=2CCC(=O)NC=2C(OC(=O)CCCCC)=CC=C1CCCCNC(O)CC1=CC=CC=C1 MEOGQDRNYXEUTH-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 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
- 238000013019 agitation Methods 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
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 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
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-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
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 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
- 125000006638 cyclopentyl carbonyl group Chemical group 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
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 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
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 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
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 230000004927 fusion Effects 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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 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
- 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
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 230000007935 neutral effect Effects 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
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 230000004526 pharmaceutical effect Effects 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 230000007017 scission Effects 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
- BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 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
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000001131 transforming effect Effects 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
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000008096 xylene Substances 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 |
|---|---|
| CH618431A5 true CH618431A5 (sv) | 1980-07-31 |
Family
ID=14810767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1634376A CH618431A5 (sv) | 1976-10-08 | 1976-12-27 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4223137A (sv) |
| JP (1) | JPS609713B2 (sv) |
| BE (1) | BE849794A (sv) |
| CA (1) | CA1074801A (sv) |
| CH (1) | CH618431A5 (sv) |
| DE (1) | DE2658544C2 (sv) |
| FR (1) | FR2378521A1 (sv) |
| GB (1) | GB1540628A (sv) |
| NL (1) | NL174041C (sv) |
| SE (1) | SE434395B (sv) |
Families Citing this family (41)
| 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 (sv) * | 1981-02-17 | 1989-05-10 | Otsuka Pharma Co Ltd | Förfarande för framställning av nya, såsom hjärtmediciner användbara s ubstituerade amid- och (mättad heterocykel)karbonylkarbostyrilderivat. |
| US4456757A (en) * | 1981-03-20 | 1984-06-26 | Asahi Kasei Kogyo Kabushiki Kaisha | Isoquinolinesulfonyl derivatives and process for the preparation thereof |
| DE3276432D1 (en) * | 1981-03-24 | 1987-07-02 | Ciba Geigy Ag | Acyl quinolinone derivatives, processes for their preparation, pharmaceutical compositions containing them and their use |
| 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 (sv) * | 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 (sv) * | 1986-10-31 | 1988-05-18 | ||
| JPS6417047U (sv) * | 1987-07-21 | 1989-01-27 | ||
| JPH0517463Y2 (sv) * | 1987-07-21 | 1993-05-11 | ||
| JPH0518510Y2 (sv) * | 1987-12-28 | 1993-05-17 | ||
| US4894219A (en) * | 1988-03-29 | 1990-01-16 | University Of Florida | Beta-agonist carbostyril derivatives, assay method and pharmacological composition |
| JPH026831U (sv) * | 1988-06-28 | 1990-01-17 | ||
| US20030229058A1 (en) | 2001-11-13 | 2003-12-11 | Moran Edmund J. | Aryl aniline beta2 adrenergic receptor agonists |
| WO2003042160A1 (en) | 2001-11-13 | 2003-05-22 | Theravance, Inc. | Aryl aniline beta-2 adrenergic receptor agonists |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US6747043B2 (en) | 2002-05-28 | 2004-06-08 | Theravance, Inc. | Alkoxy aryl β2 adrenergic receptor agonists |
| EP1565472A2 (en) * | 2002-11-27 | 2005-08-24 | Artesian Therapeutics, Inc. | Compounds with mixed pde-inhibitory and beta-adrenergic antagonist or partial agonist activity for treatment of heart failure |
| 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 |
| EP1789394A1 (de) * | 2004-05-13 | 2007-05-30 | Boehringer Ingelheim International Gmbh | Hydroxy-substituierte benzkondensierte heterozyklen als betaagonisten zur behandlung von atemwegserkrankungen |
| US7307076B2 (en) | 2004-05-13 | 2007-12-11 | Boehringer Ingelheim International Gmbh | Beta agonists for the treatment of respiratory diseases |
| JP2008501705A (ja) | 2004-06-03 | 2008-01-24 | セラヴァンス， インコーポレーテッド | ジアミンβ２アドレナリン作用性レセプターアゴニスト |
| US7566785B2 (en) | 2004-09-10 | 2009-07-28 | Theravance, Inc. | Amidine substituted aryl aniline compounds |
| 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 |
| US9784726B2 (en) | 2013-01-08 | 2017-10-10 | Atrogi Ab | Screening method, a kit, a method of treatment and a compound for use in a method of treatment |
| GB201714734D0 (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 |
| GB201714736D0 (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 |
| 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 (sv) * | 1973-12-26 | 1978-04-04 | ||
| US4026897A (en) * | 1974-01-31 | 1977-05-31 | Otsuka Pharmaceutical Company | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxycarbostyril derivatives |
| 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 |
| 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 FR FR7638918A patent/FR2378521A1/fr active Granted
- 1976-12-23 BE BE173581A patent/BE849794A/xx not_active IP Right Cessation
- 1976-12-23 SE SE7614539A patent/SE434395B/sv not_active IP Right Cessation
- 1976-12-23 CA CA268,691A patent/CA1074801A/en not_active Expired
- 1976-12-23 DE DE2658544A patent/DE2658544C2/de not_active Expired
- 1976-12-23 NL NLAANVRAGE7614329,A patent/NL174041C/xx not_active IP Right Cessation
- 1976-12-23 GB GB53966/76A patent/GB1540628A/en not_active Expired
- 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 |
|---|---|
| AU2085576A (en) | 1978-04-06 |
| US4223137A (en) | 1980-09-16 |
| GB1540628A (en) | 1979-02-14 |
| NL174041C (nl) | 1984-04-16 |
| BE849794A (fr) | 1977-04-15 |
| DE2658544C2 (de) | 1985-10-03 |
| JPS5346983A (en) | 1978-04-27 |
| SE434395B (sv) | 1984-07-23 |
| JPS609713B2 (ja) | 1985-03-12 |
| FR2378521B1 (sv) | 1979-06-29 |
| FR2378521A1 (fr) | 1978-08-25 |
| NL174041B (nl) | 1983-11-16 |
| DE2658544A1 (de) | 1978-04-13 |
| NL7614329A (nl) | 1978-04-11 |
| CA1074801A (en) | 1980-04-01 |
| SE7614539L (sv) | 1978-04-09 |
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