DK142621B - Analogifremgangsmåde til fremstilling af pyrimido(4,5-b)quinolin-4(3H)-on-2-carboxylsyre-forbindelser eller farmaceutisk acceptable kationsalte deraf. - Google Patents
Analogifremgangsmåde til fremstilling af pyrimido(4,5-b)quinolin-4(3H)-on-2-carboxylsyre-forbindelser eller farmaceutisk acceptable kationsalte deraf. Download PDFInfo
- Publication number
- DK142621B DK142621B DK200974AA DK200974A DK142621B DK 142621 B DK142621 B DK 142621B DK 200974A A DK200974A A DK 200974AA DK 200974 A DK200974 A DK 200974A DK 142621 B DK142621 B DK 142621B
- Authority
- DK
- Denmark
- Prior art keywords
- quinoline
- decomp
- mixture
- ethyl
- filtered
- Prior art date
Links
- -1 cation salts Chemical class 0.000 title claims description 25
- UHYQLALXNODRFC-UHFFFAOYSA-N 4-oxo-1h-pyrimido[4,5-b]quinoline-2-carboxylic acid Chemical class C1=CC=C2C=C(C(=O)NC(C(=O)O)=N3)C3=NC2=C1 UHYQLALXNODRFC-UHFFFAOYSA-N 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 150000002912 oxalic acid derivatives Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 239000000203 mixture Substances 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VLCMRTMCMQJSKM-UHFFFAOYSA-N phenyl-[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CN=C2C(C(F)(F)F)=CC=CC2=C1C1=CC=CC=C1 VLCMRTMCMQJSKM-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 239000000376 reactant Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- GXZOXGRLLFZVGF-UHFFFAOYSA-N 2-aminoquinoline-3-carboxamide Chemical compound C1=CC=C2N=C(N)C(C(=O)N)=CC2=C1 GXZOXGRLLFZVGF-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 7
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 229940124630 bronchodilator Drugs 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229960000265 cromoglicic acid Drugs 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- KKORZNPFZXORNH-UHFFFAOYSA-N 4-oxo-3h-quinoline-2-carboxylic acid Chemical compound C1=CC=C2C(=O)CC(C(=O)O)=NC2=C1 KKORZNPFZXORNH-UHFFFAOYSA-N 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- AAZKQXRGMFBMCF-UHFFFAOYSA-N 2-amino-6,7-dimethoxyquinoline-3-carboxamide Chemical compound NC(=O)C1=C(N)N=C2C=C(OC)C(OC)=CC2=C1 AAZKQXRGMFBMCF-UHFFFAOYSA-N 0.000 description 2
- FZAWUSJCQYKIHR-UHFFFAOYSA-N 2-amino-6-methoxyquinoline-3-carboxamide Chemical compound N1=C(N)C(C(N)=O)=CC2=CC(OC)=CC=C21 FZAWUSJCQYKIHR-UHFFFAOYSA-N 0.000 description 2
- FXWFZIRWWNPPOV-UHFFFAOYSA-N 2-aminobenzaldehyde Chemical compound NC1=CC=CC=C1C=O FXWFZIRWWNPPOV-UHFFFAOYSA-N 0.000 description 2
- PUBYDOJONNWFJJ-UHFFFAOYSA-N 2-aminoquinoline-3-carboxylic acid Chemical class C1=CC=C2C=C(C(O)=O)C(N)=NC2=C1 PUBYDOJONNWFJJ-UHFFFAOYSA-N 0.000 description 2
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 2
- YWSPWKXREVSQCA-UHFFFAOYSA-N 4,5-dimethoxy-2-nitrobenzaldehyde Chemical compound COC1=CC(C=O)=C([N+]([O-])=O)C=C1OC YWSPWKXREVSQCA-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- QGZKFCXPGDEADX-UHFFFAOYSA-N O-ethyl 7-methyl-4-oxo-3H-pyrimido[4,5-b]quinoline-2-carbothioate Chemical compound CC=1C=C2C=C3C(=NC2=CC=1)N=C(NC3=O)C(=S)OCC QGZKFCXPGDEADX-UHFFFAOYSA-N 0.000 description 2
- KUGRPPRAQNPSQD-UHFFFAOYSA-N OOOOO Chemical compound OOOOO KUGRPPRAQNPSQD-UHFFFAOYSA-N 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000150 Sympathomimetic Substances 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- ATNOAWAQFYGAOY-GPTZEZBUSA-J [Na+].[Na+].[Na+].[Na+].Cc1cc(ccc1\N=N\c1ccc2c(cc(c(N)c2c1O)S([O-])(=O)=O)S([O-])(=O)=O)-c1ccc(\N=N\c2ccc3c(cc(c(N)c3c2O)S([O-])(=O)=O)S([O-])(=O)=O)c(C)c1 Chemical compound [Na+].[Na+].[Na+].[Na+].Cc1cc(ccc1\N=N\c1ccc2c(cc(c(N)c2c1O)S([O-])(=O)=O)S([O-])(=O)=O)-c1ccc(\N=N\c2ccc3c(cc(c(N)c3c2O)S([O-])(=O)=O)S([O-])(=O)=O)c(C)c1 ATNOAWAQFYGAOY-GPTZEZBUSA-J 0.000 description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- JBRDALJZMUEMPV-UHFFFAOYSA-N ethyl 4-oxo-1h-pyrimido[4,5-b]quinoline-2-carboxylate Chemical compound C1=CC=C2N=C(NC(C(=O)OCC)=NC3=O)C3=CC2=C1 JBRDALJZMUEMPV-UHFFFAOYSA-N 0.000 description 2
- 229960003699 evans blue Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 230000000521 hyperimmunizing effect Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 229940039009 isoproterenol Drugs 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- KIDJDJMACBOHKQ-UHFFFAOYSA-N pirolate Chemical compound COC1=C(OC)C=C2N=C(NC(C(=O)OCC)=NC3=O)C3=CC2=C1 KIDJDJMACBOHKQ-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 1
- QBYSISHGTFQZKT-UHFFFAOYSA-N 2,4-dioxo-1h-pyrimido[4,5-b]quinoline-5-carboxylic acid Chemical compound N1C(=O)NC(=O)C2=C1N=C1C=CC=CC1=C2C(=O)O QBYSISHGTFQZKT-UHFFFAOYSA-N 0.000 description 1
- HEQOJEGTZCTHCF-UHFFFAOYSA-N 2-amino-1-phenylethanone Chemical compound NCC(=O)C1=CC=CC=C1 HEQOJEGTZCTHCF-UHFFFAOYSA-N 0.000 description 1
- NTKKVZTVKQWBJN-UHFFFAOYSA-N 2-amino-5-chloroquinoline-3-carboxamide Chemical compound C1=CC=C2N=C(N)C(C(=O)N)=CC2=C1Cl NTKKVZTVKQWBJN-UHFFFAOYSA-N 0.000 description 1
- RNEANOJBDLVBRF-UHFFFAOYSA-N 2-amino-6-chlorobenzaldehyde Chemical compound NC1=CC=CC(Cl)=C1C=O RNEANOJBDLVBRF-UHFFFAOYSA-N 0.000 description 1
- LXUATMNYUKVMFT-UHFFFAOYSA-N 2-amino-6-chloroquinoline-3-carboxamide Chemical compound ClC1=CC=C2N=C(N)C(C(=O)N)=CC2=C1 LXUATMNYUKVMFT-UHFFFAOYSA-N 0.000 description 1
- HQCJPLVCEVRXIE-UHFFFAOYSA-N 2-amino-6-fluoroquinoline-3-carboxamide Chemical compound FC1=CC=C2N=C(N)C(C(=O)N)=CC2=C1 HQCJPLVCEVRXIE-UHFFFAOYSA-N 0.000 description 1
- YJKWRJPXNSOYTG-UHFFFAOYSA-N 2-amino-7,8-dimethoxyquinoline-3-carboxamide Chemical compound C1=C(C(N)=O)C(N)=NC2=C(OC)C(OC)=CC=C21 YJKWRJPXNSOYTG-UHFFFAOYSA-N 0.000 description 1
- GZPSTDRRDOVICV-UHFFFAOYSA-N 2-methyl-1h-pyrimido[4,5-b]quinolin-4-one Chemical compound C1=CC=C2N=C(NC(C)=NC3=O)C3=CC2=C1 GZPSTDRRDOVICV-UHFFFAOYSA-N 0.000 description 1
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
- VHXOKHNXAGVMJI-UHFFFAOYSA-N 3,4-dimethoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C(C=O)C([N+]([O-])=O)=C1OC VHXOKHNXAGVMJI-UHFFFAOYSA-N 0.000 description 1
- NWFZLVBPKOSSBY-UHFFFAOYSA-N 3-(5-chloro-2-nitrophenyl)-2-cyanoprop-2-enamide Chemical compound NC(=O)C(C#N)=CC1=CC(Cl)=CC=C1[N+]([O-])=O NWFZLVBPKOSSBY-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- JKWFOUAOSIGNKD-UHFFFAOYSA-N 4-ethoxy-5-methoxy-2-nitrobenzaldehyde Chemical compound CCOC1=CC([N+]([O-])=O)=C(C=O)C=C1OC JKWFOUAOSIGNKD-UHFFFAOYSA-N 0.000 description 1
- ORCGMGUNVGVHDN-UHFFFAOYSA-N 4-fluoro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1C=O ORCGMGUNVGVHDN-UHFFFAOYSA-N 0.000 description 1
- SWGPIDCNYAYXMJ-UHFFFAOYSA-N 5-chloro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1C=O SWGPIDCNYAYXMJ-UHFFFAOYSA-N 0.000 description 1
- KKAFVHUJZPVWND-UHFFFAOYSA-N 5-fluoro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C=O KKAFVHUJZPVWND-UHFFFAOYSA-N 0.000 description 1
- BNTDDWPHSMILHQ-UHFFFAOYSA-N 5-methoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1 BNTDDWPHSMILHQ-UHFFFAOYSA-N 0.000 description 1
- CEHIZHJVEUNKPQ-UHFFFAOYSA-N 6,7-dimethoxyquinolin-2-amine Chemical compound C1=C(N)N=C2C=C(OC)C(OC)=CC2=C1 CEHIZHJVEUNKPQ-UHFFFAOYSA-N 0.000 description 1
- KAPAJCPOBXIQRP-UHFFFAOYSA-N 6-amino-1,3-benzodioxole-5-carbaldehyde Chemical compound C1=C(C=O)C(N)=CC2=C1OCO2 KAPAJCPOBXIQRP-UHFFFAOYSA-N 0.000 description 1
- WJSOYUGCRXNGND-UHFFFAOYSA-N 6-amino-[1,3]dioxolo[4,5-g]quinoline-7-carboxamide Chemical compound C1=C2N=C(N)C(C(=O)N)=CC2=CC2=C1OCO2 WJSOYUGCRXNGND-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241001239379 Calophysus macropterus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241001481833 Coryphaena hippurus Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920001076 Cutan Polymers 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 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 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- DAOANAATJZWTSJ-UHFFFAOYSA-N N-Decanoylmorpholine Chemical compound CCCCCCCCCC(=O)N1CCOCC1 DAOANAATJZWTSJ-UHFFFAOYSA-N 0.000 description 1
- 241001400033 Omia Species 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical group OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
- ZNIJQCQWACHEKI-UHFFFAOYSA-N ethyl 8,9-dimethoxy-4-oxo-1h-pyrimido[4,5-b]quinoline-2-carboxylate Chemical compound COC1=CC=C2C=C(C(=O)NC(C(=O)OCC)=N3)C3=NC2=C1OC ZNIJQCQWACHEKI-UHFFFAOYSA-N 0.000 description 1
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000010952 in-situ formation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- ACYBVNYNIZTUIL-UHFFFAOYSA-N n'-benzylethane-1,2-diamine Chemical compound NCCNCC1=CC=CC=C1 ACYBVNYNIZTUIL-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
- 239000006199 nebulizer Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000012256 powdered iron Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- LTIAEPYUMKCFJZ-UHFFFAOYSA-N pyrimido[4,5-b]quinoline Chemical compound N1=CN=CC2=CC3=CC=CC=C3N=C21 LTIAEPYUMKCFJZ-UHFFFAOYSA-N 0.000 description 1
- BREADKIWRGJCQJ-UHFFFAOYSA-N pyrimido[5,4-b]quinoline Chemical class C1=NC=NC2=CC3=CC=CC=C3N=C21 BREADKIWRGJCQJ-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WZODLFCLKIXWGA-UHFFFAOYSA-N sodium 4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3-methylphenyl]-2-methylphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonic acid Chemical compound CC1=C(C=CC(=C1)C2=CC(=C(C=C2)N=NC3=C(C4=C(C=C3)C(=CC(=C4N)S(=O)(=O)O)S(=O)(=O)O)O)C)N=NC5=C(C6=C(C=C5)C(=CC(=C6N)S(=O)(=O)O)S(=O)(=O)O)O.[Na+] WZODLFCLKIXWGA-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK387477A DK387477A (da) | 1973-04-13 | 1977-08-31 | Analogifremgangsmade til fremstilling af 2-hydroxyethyl-7,8-dimethoxypyrimido(4,5b)-quinolin-4(3h)-on-2-carboxylat |
| DK387377A DK387377A (da) | 1973-04-13 | 1977-08-31 | Analogifremgangsmade til fremstilling af 2-alkylpyrimido-(4,5-b)quinolin-4(3h)-onforbindelser |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35102573A | 1973-04-13 | 1973-04-13 | |
| US35102573 | 1973-04-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK142621B true DK142621B (da) | 1980-12-01 |
| DK142621C DK142621C (enrdf_load_stackoverflow) | 1981-08-03 |
Family
ID=23379271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK200974AA DK142621B (da) | 1973-04-13 | 1974-04-10 | Analogifremgangsmåde til fremstilling af pyrimido(4,5-b)quinolin-4(3H)-on-2-carboxylsyre-forbindelser eller farmaceutisk acceptable kationsalte deraf. |
Country Status (23)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4011324A (en) * | 1976-01-20 | 1977-03-08 | Pfizer Inc. | Esters and amides of pyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylic acids as antiulcer agents |
| DE2757915A1 (de) * | 1976-12-28 | 1978-07-06 | Mitsubishi Yuka Pharma | Pyrimidochinoxalinderivate, verfahren zur herstellung derselben und arzneimittel zur behandlung von allergischem asthma |
| JPS59210071A (ja) * | 1982-12-30 | 1984-11-28 | バイオメジヤ−・インコ−ポレ−テツド | 抗ウイルス作用を有する化合物 |
| ES2058527T3 (es) * | 1988-06-16 | 1994-11-01 | Smith Kline French Lab | Derivados de pirimidina condensados procedimiento y compuestos intermedios para su preparacion y composiciones farmaceuticas que los contienen. |
| FR2682378B1 (fr) * | 1991-10-10 | 1995-04-07 | Bellon Laboratoires | Nouveaux derives de l'acide fluoroquinoleine carboxylique-3 et leur preparation. |
| FR2703681B1 (fr) * | 1993-04-08 | 1995-05-12 | Bellon Labor Sa Roger | Procede de preparation de fluoro-6-halogeno-2 quinoleine |
| JP2006503094A (ja) * | 2002-10-16 | 2006-01-26 | スミスクライン ビーチャム コーポレーション | 化合物 |
| WO2021065250A1 (ja) * | 2019-09-30 | 2021-04-08 | 富士フイルム株式会社 | 着色樹脂粒子分散物、インク、インクセット、インクジェット捺染方法、油溶性染料の製造方法、及び捺染物 |
-
1973
- 1973-12-03 GB GB5590073A patent/GB1458205A/en not_active Expired
-
1974
- 1974-01-01 AR AR253237A patent/AR205342A1/es active
- 1974-01-01 AR AR257178A patent/AR205556A1/es active
- 1974-01-01 AR AR257177A patent/AR207459A1/es active
- 1974-04-04 IL IL44569A patent/IL44569A/xx unknown
- 1974-04-04 NO NO741231A patent/NO139735C/no unknown
- 1974-04-10 ES ES425238A patent/ES425238A1/es not_active Expired
- 1974-04-10 FI FI1095/74A patent/FI55658C/fi active
- 1974-04-10 NL NLAANVRAGE7404894,A patent/NL170285C/xx not_active IP Right Cessation
- 1974-04-10 DK DK200974AA patent/DK142621B/da not_active IP Right Cessation
- 1974-04-10 YU YU1016/74A patent/YU36960B/xx unknown
- 1974-04-11 IE IE781/74A patent/IE41673B1/en unknown
- 1974-04-11 CH CH511074A patent/CH619950A5/fr not_active IP Right Cessation
- 1974-04-11 BE BE1005874A patent/BE813571A/xx not_active IP Right Cessation
- 1974-04-11 DD DD177859A patent/DD111207A5/xx unknown
- 1974-04-11 CA CA197,461A patent/CA1027945A/en not_active Expired
- 1974-04-11 DE DE2418498A patent/DE2418498A1/de not_active Ceased
- 1974-04-11 ZA ZA00742351A patent/ZA742351B/xx unknown
- 1974-04-12 LU LU69855A patent/LU69855A1/xx unknown
- 1974-04-12 HU HU74PI00000413A patent/HU171157B/hu unknown
- 1974-04-12 FR FR7413092A patent/FR2225166B1/fr not_active Expired
- 1974-04-13 JP JP49041582A patent/JPS5018481A/ja active Pending
- 1974-04-13 RO RO7478412A patent/RO64918A/ro unknown
- 1974-04-13 BG BG026410A patent/BG25988A3/xx unknown
- 1974-04-16 AT AT315174A patent/AT342596B/de not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IE59309B1 (en) | New quinazoline derivatives, process for their production and pharmaceutical compositions comprising them | |
| IE55156B1 (en) | Pharmacologically active pyrazolo(4,3-c)pyridines | |
| NZ252098A (en) | 1-aryl-3-piperazino indane derivatives and medicaments | |
| DK142621B (da) | Analogifremgangsmåde til fremstilling af pyrimido(4,5-b)quinolin-4(3H)-on-2-carboxylsyre-forbindelser eller farmaceutisk acceptable kationsalte deraf. | |
| MX2007012083A (es) | Tetrahidro-piridoazepin-8-onas y compuestos relacionados para el tratamiento de la esquizofrenia. | |
| NO160995B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive bis -(4-aminofenyl)-sulfoner. | |
| AU681310B2 (en) | 2,7-substituted octahydro-1h-pyrido{1,2-a}pyrazine derivatives | |
| KR100880093B1 (ko) | 페닐-피페라진 메탄온 유도체 | |
| DK146689B (da) | Analogifremgangsmaade til fremstilling af 1',2',3',4'-tetrahydro-spiro(imidazolidin-4,4'-quinolin eller -pyrido(2,3-b)pyridin)-2,5-dion-forbindelser eller syreadditionssalte deraf | |
| NO164351B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive 5-alkyl-l-fenyl-2-piperazinoalkylpyrazolin-3-on-forbindelser. | |
| KR100485020B1 (ko) | 옥타하이드로-2Ｈ-피리도[1,2-ａ]피라진 화합물, 이들의 제조방법 및 이들을 함유하는 약제학적 조성물 | |
| US4273773A (en) | Antihypertensive tricyclic isoindole derivatives | |
| Hall et al. | Quinoline derivatives as antiallergy agents. 2. Fused-ring quinaldic acids | |
| Roth et al. | 5-Arylthiopyrimidines. III. Cyclization of 4-hydroxy derivatives to 10H-pyrimido [5, 4-b][1, 4] benzothiazines (1, 3-diazaphenothiazines) | |
| US3978064A (en) | 3-Aminomethylene-6,7-dimethoxy-2-methyl-4-oxo-1,2,3,4-tetrahydro-1-quinoline carboxylic acid esters and intermediates leading thereto | |
| EP0127412B1 (en) | Imidazolidinedione derivatives | |
| FI59097B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara pyrimido(4,5-b)kinolin-4(3h)-on-2-karboxylsyraderivat | |
| FI65620C (fi) | Foerfarande foer framstaellning av antiallergiska 9-aminopyrido(1,2-a)pyrimidiner | |
| KR910002564B1 (ko) | 헥사하이드로피롤로[2,1-a]이소퀴놀린 유도체의 제조방법 | |
| NZ201642A (en) | 1-phenylindazol-3-one derivatives and pharmaceutical compositions | |
| CA1194869A (en) | [2-[(nitropyridinyl) amino] phenyl] arylmethanones in a process for preparing pyrido [1,4] benzodiazepines | |
| US5512566A (en) | Tricyclic compounds having affinity for the 5-HT1A receptor | |
| CA2005547C (en) | Derivatives of 1,7' (imidazo-(1,2-a)-pyridine)5'-(6'h)ones | |
| NO131345B (enrdf_load_stackoverflow) | ||
| Nemazany et al. | A new and efficient route to amino derivatives of [1, 6]‐and [2, 7] naphthyridones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |