JPS642591B2 - - Google Patents
Info
- Publication number
- JPS642591B2 JPS642591B2 JP5376881A JP5376881A JPS642591B2 JP S642591 B2 JPS642591 B2 JP S642591B2 JP 5376881 A JP5376881 A JP 5376881A JP 5376881 A JP5376881 A JP 5376881A JP S642591 B2 JPS642591 B2 JP S642591B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- chlorine
- hydrogen
- formula
- tetrahydroisoquinoline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 72
- 239000000460 chlorine Chemical group 0.000 claims description 47
- 229910052801 chlorine Chemical group 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 37
- -1 nitro, methyl Chemical group 0.000 claims description 36
- 150000002431 hydrogen Chemical class 0.000 claims description 25
- UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 229910052783 alkali metal Inorganic materials 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 13
- PVMUVDSEICYOMA-UHFFFAOYSA-N n-chlorosulfonylsulfamoyl chloride Chemical compound ClS(=O)(=O)NS(Cl)(=O)=O PVMUVDSEICYOMA-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 230000000269 nucleophilic effect Effects 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 2
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims description 2
- 230000014509 gene expression Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- 239000000243 solution Substances 0.000 description 17
- AGLUHFDQESLMFH-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)NCCC2=C1 AGLUHFDQESLMFH-UHFFFAOYSA-N 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- 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 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 9
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 8
- 150000001448 anilines Chemical class 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- VROHMYFSWKZSPU-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-1-thiol Chemical class C1=CC=C2C(S)NCCC2=C1 VROHMYFSWKZSPU-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 238000007040 multi-step synthesis reaction Methods 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 4
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 239000008024 pharmaceutical diluent Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- MULMLDROTQLKML-UHFFFAOYSA-N 2-acetyl-3,4-dihydro-1h-isoquinoline-7-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2CN(C(=O)C)CCC2=C1 MULMLDROTQLKML-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- WKVZMKDXJFCMMD-UVWUDEKDSA-L (5ar,8ar,9r)-5-[[(2r,4ar,6r,7r,8r,8as)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one;azanide;n,3-bis(2-chloroethyl)-2-ox Chemical compound [NH2-].[NH2-].Cl[Pt+2]Cl.ClCCNP1(=O)OCCCN1CCCl.COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C(O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 WKVZMKDXJFCMMD-UVWUDEKDSA-L 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical class COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- FMRFUKZPHGBWHF-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-1-ol Chemical compound C1=CC=C2C(O)NCCC2=C1 FMRFUKZPHGBWHF-UHFFFAOYSA-N 0.000 description 1
- MGFREDWKELGWML-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-2-ium;chloride Chemical compound [Cl-].C1=CC=C2C[NH2+]CCC2=C1 MGFREDWKELGWML-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- PDYUNNFIOWTXLS-UHFFFAOYSA-N 1-(3,4,4a,5-tetrahydro-1h-isoquinolin-2-yl)ethanone Chemical class C1C=CC=C2CN(C(=O)C)CCC21 PDYUNNFIOWTXLS-UHFFFAOYSA-N 0.000 description 1
- OZGKFTZRSRXOMV-UHFFFAOYSA-N 1-(3,4-dihydro-1H-isoquinolin-2-yl)ethanone 1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=CC=CC=C12.C1N(CCC2=CC=CC=C12)C(C)=O OZGKFTZRSRXOMV-UHFFFAOYSA-N 0.000 description 1
- JBPPSLURCSFQDH-UHFFFAOYSA-N 1-(3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=CC=C2CN(C(=O)C)CCC2=C1 JBPPSLURCSFQDH-UHFFFAOYSA-N 0.000 description 1
- MATYZNMRPBYULY-UHFFFAOYSA-N 1-(8-chloro-3,4-dihydro-1h-isoquinolin-2-yl)ethanone Chemical compound C1=CC(Cl)=C2CN(C(=O)C)CCC2=C1 MATYZNMRPBYULY-UHFFFAOYSA-N 0.000 description 1
- GSRGJNHQNBHREF-UHFFFAOYSA-N 1-chloro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2C(Cl)NCCC2=C1 GSRGJNHQNBHREF-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- CYXIKYKBLDZZNW-UHFFFAOYSA-N 2-Chloro-1,1,1-trifluoroethane Chemical compound FC(F)(F)CCl CYXIKYKBLDZZNW-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- FMQJLOYDWUFNRO-UHFFFAOYSA-N 2-acetyl-5-chloro-3,4-dihydro-1h-isoquinoline-7-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2CN(C(=O)C)CCC2=C1Cl FMQJLOYDWUFNRO-UHFFFAOYSA-N 0.000 description 1
- PLVZEEQVUNCYBK-UHFFFAOYSA-N 2-acetyl-5-chloro-3,4-dihydro-1h-isoquinoline-8-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=C2CN(C(=O)C)CCC2=C1Cl PLVZEEQVUNCYBK-UHFFFAOYSA-N 0.000 description 1
- NSTBLRBRISSHNZ-UHFFFAOYSA-N 2-acetyl-5-methyl-3,4-dihydro-1h-isoquinoline-6-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2CN(C(=O)C)CCC2=C1C NSTBLRBRISSHNZ-UHFFFAOYSA-N 0.000 description 1
- IYVNIJXWWXAROM-UHFFFAOYSA-N 2-acetyl-6-chloro-3,4-dihydro-1h-isoquinoline-5-sulfonyl chloride Chemical compound C1=CC(Cl)=C(S(Cl)(=O)=O)C2=C1CN(C(=O)C)CC2 IYVNIJXWWXAROM-UHFFFAOYSA-N 0.000 description 1
- NSXCDSAFCAFQMM-UHFFFAOYSA-N 2-acetyl-7-bromo-3,4-dihydro-1h-isoquinoline-5-sulfonyl chloride Chemical compound C1=C(Br)C=C(S(Cl)(=O)=O)C2=C1CN(C(=O)C)CC2 NSXCDSAFCAFQMM-UHFFFAOYSA-N 0.000 description 1
- OMTNVLWKFRGEFK-UHFFFAOYSA-N 2-acetyl-7-chloro-3,4-dihydro-1h-isoquinoline-8-sulfonyl chloride Chemical compound C1=C(Cl)C(S(Cl)(=O)=O)=C2CN(C(=O)C)CCC2=C1 OMTNVLWKFRGEFK-UHFFFAOYSA-N 0.000 description 1
- YXWXVRNARIWPQC-UHFFFAOYSA-N 2-acetyl-8-chloro-3,4-dihydro-1H-isoquinoline-7-sulfonyl chloride 7-methoxyisoquinoline Chemical compound COC1=CC=C2C=CN=CC2=C1.C(C)(=O)N1CC2=C(C(=CC=C2CC1)S(=O)(=O)Cl)Cl YXWXVRNARIWPQC-UHFFFAOYSA-N 0.000 description 1
- VPMKHGVPUCZCGT-UHFFFAOYSA-N 2-acetyl-8-chloro-3,4-dihydro-1h-isoquinoline-5-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C2=C1CN(C(=O)C)CC2 VPMKHGVPUCZCGT-UHFFFAOYSA-N 0.000 description 1
- BLUDQYSSDUKOLU-UHFFFAOYSA-N 2-acetyl-8-chloro-3,4-dihydro-1h-isoquinoline-7-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C(Cl)=C2CN(C(=O)C)CCC2=C1 BLUDQYSSDUKOLU-UHFFFAOYSA-N 0.000 description 1
- SJKFSPMCULOHJC-UHFFFAOYSA-N 2-chloro-1-(2-isocyanatoethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCN=C=O)C(Cl)=C1 SJKFSPMCULOHJC-UHFFFAOYSA-N 0.000 description 1
- LNEVUNYUJNORRV-UHFFFAOYSA-N 2-chloro-4-methoxyaniline Chemical compound COC1=CC=C(N)C(Cl)=C1 LNEVUNYUJNORRV-UHFFFAOYSA-N 0.000 description 1
- IOYIDSMWPLNHRC-UHFFFAOYSA-N 2h-isoquinoline-1-thione Chemical class C1=CC=C2C(S)=NC=CC2=C1 IOYIDSMWPLNHRC-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OHOZWCJUZQXMAW-UHFFFAOYSA-N 5-chloro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=C1C=CC=C2Cl OHOZWCJUZQXMAW-UHFFFAOYSA-N 0.000 description 1
- FFGZGGGYWZLXPL-UHFFFAOYSA-N 5-chloro-7-methoxy-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1CNC(=O)C2=CC(OC)=CC(Cl)=C21 FFGZGGGYWZLXPL-UHFFFAOYSA-N 0.000 description 1
- YJNKVSVKLAVIMU-UHFFFAOYSA-N 5-nitro-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=C1C=CC=C2[N+](=O)[O-] YJNKVSVKLAVIMU-UHFFFAOYSA-N 0.000 description 1
- DGSJGBOBESCDCM-UHFFFAOYSA-N 6-chloro-8-methoxyisoquinoline Chemical compound C1=NC=C2C(OC)=CC(Cl)=CC2=C1 DGSJGBOBESCDCM-UHFFFAOYSA-N 0.000 description 1
- PNNUXNXZDJVGSB-UHFFFAOYSA-N 7-methoxyisoquinoline Chemical compound C1=CN=CC2=CC(OC)=CC=C21 PNNUXNXZDJVGSB-UHFFFAOYSA-N 0.000 description 1
- PYSJYEZRPVRRLV-UHFFFAOYSA-N 8-chloro-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.C1CNCC2=C1C=CC=C2Cl PYSJYEZRPVRRLV-UHFFFAOYSA-N 0.000 description 1
- YYTANQIIJAWDDI-UHFFFAOYSA-N 8-chloro-6-methoxyisoquinoline Chemical compound C1=NC=CC2=CC(OC)=CC(Cl)=C21 YYTANQIIJAWDDI-UHFFFAOYSA-N 0.000 description 1
- XBYNDCJUZDBRGX-UHFFFAOYSA-N 8-chloroisoquinolin-7-ol Chemical compound C1=CN=CC2=C(Cl)C(O)=CC=C21 XBYNDCJUZDBRGX-UHFFFAOYSA-N 0.000 description 1
- ZNMOGEZXEJVMOB-UHFFFAOYSA-N 8-chloroisoquinoline-7-thiol Chemical compound C1=CN=CC2=C(Cl)C(S)=CC=C21 ZNMOGEZXEJVMOB-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000007192 Meerwein reaction reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OATSQCXMYKYFQO-UHFFFAOYSA-N S-methyl thioacetate Chemical class CSC(C)=O OATSQCXMYKYFQO-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical class COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical class COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960002816 potassium chloride Drugs 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 239000012991 xanthate Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14002180A | 1980-04-14 | 1980-04-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56161374A JPS56161374A (en) | 1981-12-11 |
| JPS642591B2 true JPS642591B2 (enExample) | 1989-01-18 |
Family
ID=22489362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5376881A Granted JPS56161374A (en) | 1980-04-14 | 1981-04-08 | Novel imidodisulfamide |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS56161374A (enExample) |
| HU (1) | HU184848B (enExample) |
| ZA (1) | ZA812403B (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109928372A (zh) * | 2019-04-12 | 2019-06-25 | 广州理文科技有限公司 | 一种双氟磺酰亚胺的制备方法 |
-
1981
- 1981-04-08 JP JP5376881A patent/JPS56161374A/ja active Granted
- 1981-04-10 ZA ZA00812403A patent/ZA812403B/xx unknown
- 1981-04-13 HU HU95681A patent/HU184848B/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA812403B (en) | 1982-06-30 |
| JPS56161374A (en) | 1981-12-11 |
| HU184848B (en) | 1984-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR850000272B1 (ko) | 1이미도 디설파미드의 제조방법 | |
| US3702849A (en) | 4-(isoquinolin-1-yl) piperazine-1-carboxylic acid esters | |
| US5482967A (en) | Condensed heterocyclic compounds, their production and use | |
| JPS6393765A (ja) | 置換されたフエニルスルホンアミド類 | |
| DK165921B (da) | 1h-imidazooe4,5-caaquinolin-5-oxyforbindelser | |
| EP0266949B1 (en) | Tetrahydroisoquinolin-2-yl derivatives of carboxylic acids as thromboxane a2 antagonists | |
| EP0343574B1 (en) | 4(1H)-quinolone derivatives | |
| EP0040990B1 (en) | Antiallergic imidodisulfamides, their preparation and pharmaceutical compositions containing them | |
| US4321254A (en) | Antiallergic imidodisulfamides | |
| EP0434999A1 (en) | Cycloheptenopyridine derivatives, process for preparation thereof and antiulcer agents containing the same | |
| EP0076559B1 (en) | Antiallergic imidosulfamides | |
| US4350685A (en) | Antiallergic imidodisulfamides | |
| EP0055899B1 (en) | Antiallergic imidodisulfamides, process for their production and pharmaceutical compositions containing them | |
| EP0538477B1 (en) | Novel cyclic aminophenylacetic acid derivative, production thereof, and immune response modulator containing the same as active ingredient | |
| JP2003516969A (ja) | ２−フェニルキノリン誘導体、その製法及び治療における使用 | |
| AU665223B2 (en) | 4-amino-3-acyl quinoline derivatives | |
| HU184848B (en) | Proces for producing imidodisulfemides and antyaliergistic pharmaceutical compositions containing them as active agents | |
| CA2301510A1 (en) | 3-alkylpyrrolo[3,2-c]quinoline derivatives | |
| JP2003526633A (ja) | ２−アリールキノリン誘導体、その製造及び治療での適用 | |
| PL111060B1 (en) | Preparation of novel isoindoline derivatives | |
| JPH0314034B2 (enExample) |