NO862372L - Fremgangsmaate for fremstilling av terapeutisk aktive kinolonderivater. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive kinolonderivater.Info
- Publication number
- NO862372L NO862372L NO862372A NO862372A NO862372L NO 862372 L NO862372 L NO 862372L NO 862372 A NO862372 A NO 862372A NO 862372 A NO862372 A NO 862372A NO 862372 L NO862372 L NO 862372L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- hydrogen
- compound
- lower alkyl
- bond
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 32
- 238000002360 preparation method Methods 0.000 title claims description 9
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 125
- 239000001257 hydrogen Substances 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 150000002431 hydrogen Chemical class 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 238000006264 debenzylation reaction Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 150000007660 quinolones Chemical class 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 150000001555 benzenes Chemical group 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- GWIZNOQICBSENV-UHFFFAOYSA-N 7-chloro-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound ClC1=CC=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 GWIZNOQICBSENV-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 3
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical class C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- 239000000203 mixture Substances 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000011928 denatured alcohol Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 17
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000012265 solid product Substances 0.000 description 14
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 13
- -1 piperiidine Chemical group 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 10
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
- 229940124530 sulfonamide Drugs 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 150000003456 sulfonamides Chemical class 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000005484 gravity Effects 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- WCFDSGHAIGTEKL-UHFFFAOYSA-N n,n-dimethylmethanesulfonamide Chemical compound CN(C)S(C)(=O)=O WCFDSGHAIGTEKL-UHFFFAOYSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- UHNHTTIUNATJKL-UHFFFAOYSA-N n-methylmethanesulfonamide Chemical compound CNS(C)(=O)=O UHNHTTIUNATJKL-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical group C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- LJVAVOYDALPTQO-UHFFFAOYSA-N 1-methyl-4-oxoquinoline-3-sulfonyl chloride Chemical compound C1=CC=C2N(C)C=C(S(Cl)(=O)=O)C(=O)C2=C1 LJVAVOYDALPTQO-UHFFFAOYSA-N 0.000 description 2
- FFQSEJVQVPWPFV-UHFFFAOYSA-N 2-[4-fluoro-2-(methylamino)phenyl]-n-methyl-2-oxoethanesulfonamide Chemical compound CNC1=CC(F)=CC=C1C(=O)CS(=O)(=O)NC FFQSEJVQVPWPFV-UHFFFAOYSA-N 0.000 description 2
- WJTCYXSIZMVHAE-UHFFFAOYSA-N 7-chloro-1-methyl-4-oxoquinoline-3-sulfonyl chloride Chemical compound C1=C(Cl)C=C2N(C)C=C(S(Cl)(=O)=O)C(=O)C2=C1 WJTCYXSIZMVHAE-UHFFFAOYSA-N 0.000 description 2
- UGLRIHGBJDZUEN-UHFFFAOYSA-N 7-chloro-6-methoxy-n,n,1-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound CN1C=C(S(=O)(=O)N(C)C)C(=O)C2=C1C=C(Cl)C(OC)=C2 UGLRIHGBJDZUEN-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- CSJAXRKDCCWCSJ-UHFFFAOYSA-N Echinopsine Chemical compound C1=CC=C2N(C)C=CC(=O)C2=C1 CSJAXRKDCCWCSJ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-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
- 244000309464 bull Species 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- POJXEDATMPDTHT-UHFFFAOYSA-N ethyl 2-amino-5-methoxybenzoate Chemical compound CCOC(=O)C1=CC(OC)=CC=C1N POJXEDATMPDTHT-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- IOSTYTUPOTYMES-UHFFFAOYSA-N methyl 4-fluoro-2-(methylamino)benzoate Chemical compound CNC1=CC(F)=CC=C1C(=O)OC IOSTYTUPOTYMES-UHFFFAOYSA-N 0.000 description 2
- MSOZHXBTQSLOQH-UHFFFAOYSA-N n,1-dimethyl-4-oxo-7-(trifluoromethyl)quinoline-3-sulfonamide Chemical compound FC(F)(F)C1=CC=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 MSOZHXBTQSLOQH-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- IBMIBJOOEWEDSN-UHFFFAOYSA-N 1,7-dimethylquinolin-4-one Chemical compound CN1C=CC(=O)C=2C1=CC(C)=CC=2 IBMIBJOOEWEDSN-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- ZYVYEJXMYBUCMN-UHFFFAOYSA-N 1-methoxy-2-methylpropane Chemical compound COCC(C)C ZYVYEJXMYBUCMN-UHFFFAOYSA-N 0.000 description 1
- OMGFCIGRZNCCKB-UHFFFAOYSA-N 1-methyl-4-oxo-7-(trifluoromethyl)quinoline-3-carboxylic acid Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(C(O)=O)C(=O)C2=C1 OMGFCIGRZNCCKB-UHFFFAOYSA-N 0.000 description 1
- CKMRUFDOPVYNHH-UHFFFAOYSA-N 1-methyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=CC=C2N(C)C=C(S(N)(=O)=O)C(=O)C2=C1 CKMRUFDOPVYNHH-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- KSWYXXNCSGVDKW-UHFFFAOYSA-N 2-(2-amino-3,4,5-trimethoxyphenyl)-n-methyl-2-oxoethanesulfonamide Chemical compound CNS(=O)(=O)CC(=O)C1=CC(OC)=C(OC)C(OC)=C1N KSWYXXNCSGVDKW-UHFFFAOYSA-N 0.000 description 1
- QWPAOVXVQJOCNO-UHFFFAOYSA-N 2-(2-amino-4-chloro-5-methoxyphenyl)-n,n-dimethyl-2-oxoethanesulfonamide Chemical compound COC1=CC(C(=O)CS(=O)(=O)N(C)C)=C(N)C=C1Cl QWPAOVXVQJOCNO-UHFFFAOYSA-N 0.000 description 1
- UUEOZBCQXXOXLN-UHFFFAOYSA-N 2-(2-amino-5-methoxy-4-methylphenyl)-n,n-dimethyl-2-oxoethanesulfonamide Chemical compound COC1=CC(C(=O)CS(=O)(=O)N(C)C)=C(N)C=C1C UUEOZBCQXXOXLN-UHFFFAOYSA-N 0.000 description 1
- QTZYTYMIRNZHSR-UHFFFAOYSA-N 2-(2-amino-5-methoxyphenyl)-n,n-dimethyl-2-oxoethanesulfonamide Chemical compound COC1=CC=C(N)C(C(=O)CS(=O)(=O)N(C)C)=C1 QTZYTYMIRNZHSR-UHFFFAOYSA-N 0.000 description 1
- QPVLGVLTMPDDGY-UHFFFAOYSA-N 2-(2-amino-5-methoxyphenyl)-n-methyl-2-oxoethanesulfonamide Chemical compound CNS(=O)(=O)CC(=O)C1=CC(OC)=CC=C1N QPVLGVLTMPDDGY-UHFFFAOYSA-N 0.000 description 1
- BGMGTOYUBPPABI-UHFFFAOYSA-N 2-[4-fluoro-2-(methylamino)phenyl]-n,n-dimethyl-2-oxoethanesulfonamide Chemical compound CNC1=CC(F)=CC=C1C(=O)CS(=O)(=O)N(C)C BGMGTOYUBPPABI-UHFFFAOYSA-N 0.000 description 1
- ALKNPNFSCRLOBJ-UHFFFAOYSA-N 2-amino-5-methoxy-4-methylbenzoic acid Chemical compound COC1=CC(C(O)=O)=C(N)C=C1C ALKNPNFSCRLOBJ-UHFFFAOYSA-N 0.000 description 1
- YKZBEIJTRNBOFF-UHFFFAOYSA-N 2-hydroxyimino-n-(4-methoxy-3-methylphenyl)acetamide Chemical compound COC1=CC=C(NC(=O)C=NO)C=C1C YKZBEIJTRNBOFF-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- NFWPZNNZUCPLAX-UHFFFAOYSA-N 4-methoxy-3-methylaniline Chemical compound COC1=CC=C(N)C=C1C NFWPZNNZUCPLAX-UHFFFAOYSA-N 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- SXCZRQXECZWRJN-UHFFFAOYSA-N 5-methoxy-6-methyl-1h-indole-2,3-dione Chemical compound C1=C(C)C(OC)=CC2=C1NC(=O)C2=O SXCZRQXECZWRJN-UHFFFAOYSA-N 0.000 description 1
- MESLPMHFLJAABF-UHFFFAOYSA-N 6,7,8-trimethoxy-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound COC1=C(OC)C=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1OC MESLPMHFLJAABF-UHFFFAOYSA-N 0.000 description 1
- YNQRXSZPPBGXNZ-UHFFFAOYSA-N 6,7,8-trimethoxy-n-methyl-4-oxo-1h-quinoline-3-sulfonamide Chemical compound COC1=C(OC)C(OC)=CC2=C(O)C(S(=O)(=O)NC)=CN=C21 YNQRXSZPPBGXNZ-UHFFFAOYSA-N 0.000 description 1
- XZMQFGBEPTUAQS-UHFFFAOYSA-N 6,7-dimethoxy-1-methyl-4-oxoquinoline-3-sulfonamide Chemical compound CN1C=C(S(N)(=O)=O)C(=O)C2=C1C=C(OC)C(OC)=C2 XZMQFGBEPTUAQS-UHFFFAOYSA-N 0.000 description 1
- RECXZBCRYVVAKV-UHFFFAOYSA-N 6-fluoro-1-methylquinolin-4-one Chemical compound FC1=CC=C2N(C)C=CC(=O)C2=C1 RECXZBCRYVVAKV-UHFFFAOYSA-N 0.000 description 1
- BYZXOYSEYWCLOK-UHFFFAOYSA-N 6-fluoro-1h-quinolin-4-one Chemical compound C1=C(F)C=C2C(O)=CC=NC2=C1 BYZXOYSEYWCLOK-UHFFFAOYSA-N 0.000 description 1
- DERWHGBXTPJCMH-UHFFFAOYSA-N 6-fluoro-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=C(F)C=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 DERWHGBXTPJCMH-UHFFFAOYSA-N 0.000 description 1
- HXZMHORBKHASRC-UHFFFAOYSA-N 6-methoxy-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=C(OC)C=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 HXZMHORBKHASRC-UHFFFAOYSA-N 0.000 description 1
- UGTQLLXFGRIQSL-UHFFFAOYSA-N 6-methoxy-n,n,1,7-tetramethyl-4-oxoquinoline-3-sulfonamide Chemical compound CN1C=C(S(=O)(=O)N(C)C)C(=O)C2=C1C=C(C)C(OC)=C2 UGTQLLXFGRIQSL-UHFFFAOYSA-N 0.000 description 1
- CJOJZXHKCVGYEZ-UHFFFAOYSA-N 6-methoxy-n,n,1-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound CN1C=C(S(=O)(=O)N(C)C)C(=O)C2=CC(OC)=CC=C21 CJOJZXHKCVGYEZ-UHFFFAOYSA-N 0.000 description 1
- ATFODIACSFPWKQ-UHFFFAOYSA-N 6-methoxy-n,n-dimethyl-4-oxo-1h-quinoline-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(C)C)=C(O)C2=CC(OC)=CC=C21 ATFODIACSFPWKQ-UHFFFAOYSA-N 0.000 description 1
- NFLHJDWXIBDNRY-UHFFFAOYSA-N 6-methoxy-n-methyl-4-oxo-1h-quinoline-3-sulfonamide Chemical compound C1=CC(OC)=CC2=C(O)C(S(=O)(=O)NC)=CN=C21 NFLHJDWXIBDNRY-UHFFFAOYSA-N 0.000 description 1
- KEUWFAMBOBMPQE-UHFFFAOYSA-N 7-chloro-1-methyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=C(Cl)C=C2N(C)C=C(S(N)(=O)=O)C(=O)C2=C1 KEUWFAMBOBMPQE-UHFFFAOYSA-N 0.000 description 1
- PSDVUIDSZMQDJU-UHFFFAOYSA-N 7-chloro-1-methylquinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=CC(=O)C2=C1 PSDVUIDSZMQDJU-UHFFFAOYSA-N 0.000 description 1
- FQCHFOWCCHOXMA-UHFFFAOYSA-N 7-chloro-6-fluoro-1-methyl-4-oxoquinoline-3-sulfonyl chloride Chemical compound FC1=C(Cl)C=C2N(C)C=C(S(Cl)(=O)=O)C(=O)C2=C1 FQCHFOWCCHOXMA-UHFFFAOYSA-N 0.000 description 1
- HHRGXDRDKKAVOD-UHFFFAOYSA-N 7-chloro-6-fluoro-1-methylquinolin-4-one Chemical compound FC1=C(Cl)C=C2N(C)C=CC(=O)C2=C1 HHRGXDRDKKAVOD-UHFFFAOYSA-N 0.000 description 1
- JVSXZJROLBGYID-UHFFFAOYSA-N 7-chloro-6-fluoro-1h-quinolin-4-one Chemical compound ClC1=C(F)C=C2C(O)=CC=NC2=C1 JVSXZJROLBGYID-UHFFFAOYSA-N 0.000 description 1
- VSRWFZNCUYWYDS-UHFFFAOYSA-N 7-chloro-6-fluoro-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound ClC1=C(F)C=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 VSRWFZNCUYWYDS-UHFFFAOYSA-N 0.000 description 1
- YFOSSZOALKVFIT-UHFFFAOYSA-N 7-chloro-6-fluoro-n,n,1-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound ClC1=C(F)C=C2C(=O)C(S(=O)(=O)N(C)C)=CN(C)C2=C1 YFOSSZOALKVFIT-UHFFFAOYSA-N 0.000 description 1
- YGATZBAHTIRPNH-UHFFFAOYSA-N 7-chloro-6-methoxy-n,n-dimethyl-4-oxo-1h-quinoline-3-sulfonamide Chemical compound CN(C)S(=O)(=O)C1=CN=C2C=C(Cl)C(OC)=CC2=C1O YGATZBAHTIRPNH-UHFFFAOYSA-N 0.000 description 1
- ODDMFBHLJXZHRU-UHFFFAOYSA-N 7-chloro-n,n,1-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound ClC1=CC=C2C(=O)C(S(=O)(=O)N(C)C)=CN(C)C2=C1 ODDMFBHLJXZHRU-UHFFFAOYSA-N 0.000 description 1
- VMEFZSNHLOWSOV-UHFFFAOYSA-N 7-fluoro-1-methylquinolin-4-one Chemical compound C1=C(F)C=C2N(C)C=CC(=O)C2=C1 VMEFZSNHLOWSOV-UHFFFAOYSA-N 0.000 description 1
- ZLHGUGJJHJJVHV-UHFFFAOYSA-N 7-fluoro-1h-quinolin-4-one Chemical compound N1C=CC(=O)C=2C1=CC(F)=CC=2 ZLHGUGJJHJJVHV-UHFFFAOYSA-N 0.000 description 1
- UWXULTKABASOFM-UHFFFAOYSA-N 7-fluoro-n,1,2-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound FC1=CC=C2C(=O)C(S(=O)(=O)NC)=C(C)N(C)C2=C1 UWXULTKABASOFM-UHFFFAOYSA-N 0.000 description 1
- MNZUOCYMACCVFI-UHFFFAOYSA-N 7-fluoro-n,1-dimethyl-4-oxo-2,3-dihydroquinoline-3-sulfonamide Chemical compound FC1=CC=C2C(=O)C(S(=O)(=O)NC)CN(C)C2=C1 MNZUOCYMACCVFI-UHFFFAOYSA-N 0.000 description 1
- NMAGSAZZLWUFAA-UHFFFAOYSA-N 7-fluoro-n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound FC1=CC=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 NMAGSAZZLWUFAA-UHFFFAOYSA-N 0.000 description 1
- PXDVDYIFXYWOKG-UHFFFAOYSA-N 7-fluoro-n,n,1,2-tetramethyl-4-oxoquinoline-3-sulfonamide Chemical compound FC1=CC=C2C(=O)C(S(=O)(=O)N(C)C)=C(C)N(C)C2=C1 PXDVDYIFXYWOKG-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ZTQBHLJFTXXKAA-UHFFFAOYSA-N O=S(=O)NCC1=CC=CC=C1 Chemical compound O=S(=O)NCC1=CC=CC=C1 ZTQBHLJFTXXKAA-UHFFFAOYSA-N 0.000 description 1
- HDUHSISAGHHYRW-UHFFFAOYSA-N [N].N1=CC=CC2=CC=CC=C21 Chemical group [N].N1=CC=CC2=CC=CC=C21 HDUHSISAGHHYRW-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- PMXXKJCISGBCGF-UHFFFAOYSA-N ethyl 2-amino-4-chloro-5-methoxybenzoate Chemical compound CCOC(=O)C1=CC(OC)=C(Cl)C=C1N PMXXKJCISGBCGF-UHFFFAOYSA-N 0.000 description 1
- CXNDMLVIXNZOTD-UHFFFAOYSA-N ethyl 2-amino-5-methoxy-4-methylbenzoate Chemical compound CCOC(=O)C1=CC(OC)=C(C)C=C1N CXNDMLVIXNZOTD-UHFFFAOYSA-N 0.000 description 1
- VLOYRWBXBBOLJW-UHFFFAOYSA-N ethyl 7-chloro-6-fluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound ClC1=C(F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 VLOYRWBXBBOLJW-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UPVUQELOASQBMY-UHFFFAOYSA-N methyl 2-amino-3,4,5-trimethoxybenzoate Chemical compound COC(=O)C1=CC(OC)=C(OC)C(OC)=C1N UPVUQELOASQBMY-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- WNIVEFLNFCUQDW-UHFFFAOYSA-N n,1,7-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound CC1=CC=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 WNIVEFLNFCUQDW-UHFFFAOYSA-N 0.000 description 1
- UMBKNZYONDDZAF-UHFFFAOYSA-N n,1-dimethyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=CC=C2C(=O)C(S(=O)(=O)NC)=CN(C)C2=C1 UMBKNZYONDDZAF-UHFFFAOYSA-N 0.000 description 1
- LXZWPOOTYKDYIS-UHFFFAOYSA-N n,n,1-trimethyl-4-oxo-7-(trifluoromethyl)quinoline-3-sulfonamide Chemical compound FC(F)(F)C1=CC=C2C(=O)C(S(=O)(=O)N(C)C)=CN(C)C2=C1 LXZWPOOTYKDYIS-UHFFFAOYSA-N 0.000 description 1
- ZRJQIWZELJNZBX-UHFFFAOYSA-N n,n,1-trimethyl-4-oxoquinoline-3-sulfonamide Chemical compound C1=CC=C2C(=O)C(S(=O)(=O)N(C)C)=CN(C)C2=C1 ZRJQIWZELJNZBX-UHFFFAOYSA-N 0.000 description 1
- NFBMFGTXIFDVGH-UHFFFAOYSA-N n-benzyl-7-chloro-1-methyl-4-oxoquinoline-3-sulfonamide Chemical compound O=C1C2=CC=C(Cl)C=C2N(C)C=C1S(=O)(=O)NCC1=CC=CC=C1 NFBMFGTXIFDVGH-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000010355 oscillation Effects 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
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000010349 pulsation 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
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 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
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- 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
- C07D215/36—Sulfur atoms
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB858515209A GB8515209D0 (en) | 1985-06-15 | 1985-06-15 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO862372D0 NO862372D0 (no) | 1986-06-13 |
| NO862372L true NO862372L (no) | 1986-12-16 |
Family
ID=10580805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO862372A NO862372L (no) | 1985-06-15 | 1986-06-13 | Fremgangsmaate for fremstilling av terapeutisk aktive kinolonderivater. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4772614A (xx) |
| EP (1) | EP0206616A3 (xx) |
| JP (1) | JPS6236361A (xx) |
| KR (1) | KR870000302A (xx) |
| CN (1) | CN86104611A (xx) |
| AU (1) | AU5838286A (xx) |
| DD (1) | DD249010A5 (xx) |
| DK (1) | DK272386A (xx) |
| ES (1) | ES8801211A1 (xx) |
| FI (1) | FI862519A (xx) |
| GB (1) | GB8515209D0 (xx) |
| GR (1) | GR861528B (xx) |
| HU (1) | HUT42073A (xx) |
| IL (1) | IL79039A0 (xx) |
| JO (1) | JO1483B1 (xx) |
| NO (1) | NO862372L (xx) |
| PH (1) | PH22992A (xx) |
| PT (1) | PT82760B (xx) |
| ZA (1) | ZA864288B (xx) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0172004B1 (en) * | 1984-08-15 | 1990-03-21 | The Boots Company PLC | Quinolinones, process for their preparation and pharmaceutical compositions containing them |
| GB8627698D0 (en) * | 1986-11-20 | 1986-12-17 | Boots Co Plc | Therapeutic agents |
| GB8726950D0 (en) * | 1987-11-18 | 1987-12-23 | Boots Co Plc | Chemical process |
| GB8804016D0 (en) * | 1988-02-22 | 1988-03-23 | Boots Co Plc | Therapeutic agents |
| EP0343574B1 (en) * | 1988-05-24 | 1994-07-27 | Kirin Beer Kabushiki Kaisha | 4(1H)-quinolone derivatives |
| GB8918952D0 (en) * | 1989-08-19 | 1989-10-04 | Boots Co Plc | Therapeutic agents |
| US5927566A (en) * | 1996-07-11 | 1999-07-27 | Aptargroup, Inc. | One-piece dispensing system and method for making same |
| CA2339484A1 (en) * | 1998-08-03 | 2000-02-17 | Robert A. O'brien | Pyridinones for the treatment of sexual dysfunction |
| US6458804B1 (en) | 2001-01-26 | 2002-10-01 | R.T. Alamo Venturesi, Llc | Methods for the treatment of central nervous system disorders in certain patient groups |
| US6562838B2 (en) * | 2001-01-26 | 2003-05-13 | R. T. Alamo Ventures I, L.L.C. | Treatment of cardiovascular disease with quinolinone enantiomers |
| US6451813B1 (en) | 2001-01-26 | 2002-09-17 | R. T. Alamo Ventures I, Llc | Treatment of gastroparesis in certain patient groups |
| AU2003276458A1 (en) * | 2002-11-07 | 2004-06-07 | Astrazeneca Ab | 2-oxo-ethanesulfonamide derivates |
| CN103864680B (zh) * | 2012-12-12 | 2015-09-02 | 王子厚 | 具有抗肿瘤活性的氯氧喹衍生物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4913185A (xx) * | 1972-06-02 | 1974-02-05 | ||
| NZ193167A (en) * | 1979-03-27 | 1984-08-24 | Boots Co Plc | Quinoline derivatives and pharmaceutical compositions |
| IE51542B1 (en) * | 1980-09-26 | 1987-01-07 | Boots Co Ltd | Therapeutic agents |
| PT79031B (en) * | 1983-08-20 | 1986-08-22 | Boots Co Plc | Therapeutic agents |
| EP0149519B1 (en) * | 1984-01-13 | 1990-06-27 | The Boots Company PLC | Use of quinolones for the manufacture of a composition for the treatment of heart failure. |
| EP0172004B1 (en) * | 1984-08-15 | 1990-03-21 | The Boots Company PLC | Quinolinones, process for their preparation and pharmaceutical compositions containing them |
-
1985
- 1985-06-15 GB GB858515209A patent/GB8515209D0/en active Pending
-
1986
- 1986-06-05 AU AU58382/86A patent/AU5838286A/en not_active Abandoned
- 1986-06-05 IL IL79039A patent/IL79039A0/xx unknown
- 1986-06-09 PH PH33870A patent/PH22992A/en unknown
- 1986-06-09 ZA ZA864288A patent/ZA864288B/xx unknown
- 1986-06-09 EP EP86304390A patent/EP0206616A3/en not_active Withdrawn
- 1986-06-10 DK DK272386A patent/DK272386A/da not_active Application Discontinuation
- 1986-06-12 GR GR861528A patent/GR861528B/el unknown
- 1986-06-12 PT PT82760A patent/PT82760B/pt unknown
- 1986-06-12 FI FI862519A patent/FI862519A/fi not_active IP Right Cessation
- 1986-06-13 DD DD86291288A patent/DD249010A5/de unknown
- 1986-06-13 HU HU862522A patent/HUT42073A/hu unknown
- 1986-06-13 ES ES556027A patent/ES8801211A1/es not_active Expired
- 1986-06-13 NO NO862372A patent/NO862372L/no unknown
- 1986-06-13 US US06/874,217 patent/US4772614A/en not_active Expired - Fee Related
- 1986-06-14 JO JO19861483A patent/JO1483B1/en active
- 1986-06-14 KR KR1019860004738A patent/KR870000302A/ko not_active Application Discontinuation
- 1986-06-16 JP JP61139954A patent/JPS6236361A/ja active Pending
- 1986-07-07 CN CN198686104611A patent/CN86104611A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL79039A0 (en) | 1986-09-30 |
| PH22992A (en) | 1989-02-24 |
| HUT42073A (en) | 1987-06-29 |
| ZA864288B (en) | 1987-01-28 |
| FI862519A (fi) | 1986-12-16 |
| EP0206616A3 (en) | 1988-06-01 |
| NO862372D0 (no) | 1986-06-13 |
| GR861528B (en) | 1986-10-10 |
| US4772614A (en) | 1988-09-20 |
| ES8801211A1 (es) | 1987-12-16 |
| DK272386D0 (da) | 1986-06-10 |
| CN86104611A (zh) | 1988-01-27 |
| KR870000302A (ko) | 1987-02-17 |
| DK272386A (da) | 1986-12-16 |
| FI862519A0 (fi) | 1986-06-12 |
| PT82760B (en) | 1988-05-19 |
| DD249010A5 (de) | 1987-08-26 |
| JO1483B1 (en) | 1988-03-10 |
| AU5838286A (en) | 1986-12-18 |
| JPS6236361A (ja) | 1987-02-17 |
| ES556027A0 (es) | 1987-12-16 |
| PT82760A (en) | 1986-07-01 |
| GB8515209D0 (en) | 1985-07-17 |
| EP0206616A2 (en) | 1986-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI83316B (fi) | Foerfarande foer framstaellning av farmaceutiskt aktiva 1,3-dihydro-2h-imidazo/4,5-b/kinolin-2-onderivat. | |
| USRE31617E (en) | Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones | |
| NO862372L (no) | Fremgangsmaate for fremstilling av terapeutisk aktive kinolonderivater. | |
| US6166040A (en) | Indole compounds | |
| AU698580B2 (en) | Serotonergic tetrahydropyridoindoles | |
| MX2007012110A (es) | Agentes del receptor de histamina h3, preparacion y usos terapeuticos. | |
| FI95369B (fi) | Menetelmä viherkaihia estävien 3-aryylikarbonyyli-1-aminoalkyyli-1H-indoliyhdisteiden valmistamiseksi | |
| US4855291A (en) | 1,4dihydroquinoline-3-carboxamides | |
| US5563147A (en) | Serotonerbic tetrahydropyridoindoles | |
| Gineinah et al. | Synthesis and Antiinflammatory Screening of Some Quinazoline and Quinazolyl‐4‐oxoquinazoline Derivatives | |
| Stadlbauers et al. | Ring closure reactions of 3‐arylhydrazonoalkyl‐quinolin‐2‐ones to 1‐aryl‐pyrazolo [4, 3‐c] quinolin‐2‐ones | |
| JPH0311067A (ja) | 興奮性アミノ酸拮抗剤 | |
| US8003670B2 (en) | Aminoalkoxy aryl sulfonamide compounds and their use as 5-HT6 ligands | |
| KR20010033609A (ko) | 테트라하이드로벤즈인돌 유도체 | |
| Aotsuka et al. | Novel and potent aldose reductase inhibitors: 4-benzyl-and 4-(benzothiazol-2-ylmethyl)-3, 4-dihydro-3-oxo-2H-1, 4-benzothiazine-2-acetic acid derivatives | |
| CA2672190C (en) | 4-(heterocyclyl)alkyl-n-(arylsulfonyl) indole compounds and their use as 5-ht6 ligands | |
| US5340814A (en) | 3-substituted methyl-2,3-dihydroimidazo[1,2-C] quinazoline derivatives, the preparation and use thereof | |
| JP3285343B2 (ja) | テトラヒドロキナゾリン−２，４−ジオンおよびそれらの治療用途 | |
| CS248720B2 (en) | Production method of quinolines | |
| FI79323B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara pyrimido/2,1-b/bensotiazoler. | |
| US4745115A (en) | Isoquinolines or benzisoquinoliner having antiinflammatory activity | |
| US4254134A (en) | Antidepressant 2-amino- and -2-(substituted amino)-cis-hexahydro-carbazoles | |
| CA1260933A (en) | Bicyclic lactams, processes for their preparation and their use, and formulations containing these compounds | |
| US3798227A (en) | Process of cyclizing alkylidene substituted aminomethylenemalonates | |
| Effland et al. | Synthesis of pyrrolo [2, 1‐c][1, 4] benzoxazepines. 1. A novel heterocyclic ring system |