NO883339L - Fremgangsmaate for fremstilling av benzimidazol-2-yl-pyridiniumforbindelser. - Google Patents
Fremgangsmaate for fremstilling av benzimidazol-2-yl-pyridiniumforbindelser.Info
- Publication number
- NO883339L NO883339L NO88883339A NO883339A NO883339L NO 883339 L NO883339 L NO 883339L NO 88883339 A NO88883339 A NO 88883339A NO 883339 A NO883339 A NO 883339A NO 883339 L NO883339 L NO 883339L
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- hydrogen
- methoxy
- trifluoromethyl
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 35
- XOPFPFXWJMHARA-UHFFFAOYSA-N 2-pyridin-1-ium-1-yl-1h-benzimidazole Chemical class C1=CC=CC=[N+]1C1=NC2=CC=CC=C2N1 XOPFPFXWJMHARA-UHFFFAOYSA-N 0.000 title claims description 5
- -1 2-[2-(2-methoxyethoxy)-ethoxy]ethoxy Chemical group 0.000 claims description 82
- 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 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 239000000460 chlorine Substances 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 210000001198 duodenum Anatomy 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 5
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 5
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 208000025865 Ulcer Diseases 0.000 claims description 4
- DGDJQEHHQMWRHZ-UHFFFAOYSA-M [1-[[4-methoxy-3-methyl-1-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]pyridin-1-ium-2-yl]methylsulfanyl]-2-methylpropan-2-yl] acetate;chloride Chemical compound [Cl-].CC(=O)OC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 DGDJQEHHQMWRHZ-UHFFFAOYSA-M 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- XDESRLRQCRHPEK-UHFFFAOYSA-M methanesulfonate;2-[4-methoxy-2-[[2-(2-methoxyethoxy)-2-methylpropyl]sulfanylmethyl]-3-methylpyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound CS([O-])(=O)=O.COCCOC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 XDESRLRQCRHPEK-UHFFFAOYSA-M 0.000 claims description 4
- JZSJUZJNIIERSG-UHFFFAOYSA-M methanesulfonate;[1-[[4-methoxy-3-methyl-1-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]pyridin-1-ium-2-yl]methylsulfanyl]-2-methylpropan-2-yl] acetate Chemical compound CS([O-])(=O)=O.CC(=O)OC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 JZSJUZJNIIERSG-UHFFFAOYSA-M 0.000 claims description 4
- 231100000397 ulcer Toxicity 0.000 claims description 4
- NIUXJOVWSZPHSE-UHFFFAOYSA-M 2-[2-[(2-ethoxy-2-methylpropyl)sulfanylmethyl]-4-methoxy-3-methylpyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;chloride Chemical compound [Cl-].CCOC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 NIUXJOVWSZPHSE-UHFFFAOYSA-M 0.000 claims description 3
- ZLRCJULKAZVXGG-UHFFFAOYSA-M 2-[2-[(2-ethoxy-2-methylpropyl)sulfanylmethyl]-4-methoxy-3-methylpyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 ZLRCJULKAZVXGG-UHFFFAOYSA-M 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229940126601 medicinal product Drugs 0.000 claims description 3
- UWGSMFUMCZTQME-UHFFFAOYSA-M methanesulfonate;2-[1-[[4-methoxy-3-methyl-1-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]pyridin-1-ium-2-yl]methylsulfanyl]-2-methylpropan-2-yl]oxyethanol Chemical compound CS([O-])(=O)=O.OCCOC(C)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 UWGSMFUMCZTQME-UHFFFAOYSA-M 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 5
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 282
- 239000000243 solution Substances 0.000 description 123
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 100
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 63
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 58
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 32
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 229940098779 methanesulfonic acid Drugs 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 27
- 229910002027 silica gel Inorganic materials 0.000 description 27
- 239000000203 mixture Substances 0.000 description 26
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
- 235000017557 sodium bicarbonate Nutrition 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- 238000002425 crystallisation Methods 0.000 description 19
- 230000008025 crystallization Effects 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 16
- 239000003480 eluent Substances 0.000 description 15
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- OWWKQFJLNQHYQS-UHFFFAOYSA-N 2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(=CC=C3N=2)C(F)(F)F)=C1C OWWKQFJLNQHYQS-UHFFFAOYSA-N 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 13
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000007789 gas Substances 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- 238000000354 decomposition reaction Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 239000007903 gelatin capsule Substances 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 7
- 238000004452 microanalysis Methods 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
- NPEFJBRHOLYMMM-UHFFFAOYSA-N 6-fluoro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(F)=CC=C3N=2)=C1C NPEFJBRHOLYMMM-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- MFLDNEOZOWBPNE-UHFFFAOYSA-N 2-[(4-ethoxy-3-methylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound CCOC1=CC=NC(CSC=2NC3=CC(=CC=C3N=2)C(F)(F)F)=C1C MFLDNEOZOWBPNE-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- 230000027119 gastric acid secretion Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000002966 varnish Substances 0.000 description 4
- WHAGSNVVBXOIGQ-UHFFFAOYSA-N 2-(chloromethyl)-4-methoxy-3-methylpyridine;hydron;chloride Chemical compound Cl.COC1=CC=NC(CCl)=C1C WHAGSNVVBXOIGQ-UHFFFAOYSA-N 0.000 description 3
- XYGPFTDBZDOQSW-UHFFFAOYSA-N 5,6-dichloro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(Cl)=C(Cl)C=C3N=2)=C1C XYGPFTDBZDOQSW-UHFFFAOYSA-N 0.000 description 3
- LKGIDNWLHBLXQN-UHFFFAOYSA-N 5,6-difluoro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC(F)=C(F)C=C3N=2)=C1C LKGIDNWLHBLXQN-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 229960000905 indomethacin Drugs 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- 239000000052 vinegar Substances 0.000 description 3
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- PNFLOSUXUNZVIW-UHFFFAOYSA-N 2-[(3-methyl-4-nitropyridin-2-yl)methylsulfanyl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound N1=CC=C([N+]([O-])=O)C(C)=C1CSC1=NC2=CC=C(C(F)(F)F)C=C2N1 PNFLOSUXUNZVIW-UHFFFAOYSA-N 0.000 description 2
- DDPFXSPTUIQFJY-UHFFFAOYSA-M 2-[4-methoxy-3-methyl-2-(2-methylprop-1-enylsulfanylmethyl)pyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;chloride Chemical compound [Cl-].CC(C)=CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 DDPFXSPTUIQFJY-UHFFFAOYSA-M 0.000 description 2
- UGYXPZQILZRKJJ-UHFFFAOYSA-N 4-methylhistamine Chemical compound CC=1NC=NC=1CCN UGYXPZQILZRKJJ-UHFFFAOYSA-N 0.000 description 2
- YQAGIRWYHRGOCY-UHFFFAOYSA-N 5,6-dichloro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(Cl)=C(Cl)C=C3N=2)=C1C YQAGIRWYHRGOCY-UHFFFAOYSA-N 0.000 description 2
- SPVMMWAWALXDSC-UHFFFAOYSA-N 5,6-difluoro-1,3-dihydrobenzimidazole-2-thione Chemical compound C1=C(F)C(F)=CC2=C1NC(=S)N2 SPVMMWAWALXDSC-UHFFFAOYSA-N 0.000 description 2
- ZUCXDOOOUADWEU-UHFFFAOYSA-N 5,6-difluoro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(F)=C(F)C=C3N=2)=C1C ZUCXDOOOUADWEU-UHFFFAOYSA-N 0.000 description 2
- HHZOBJBWXJSCSN-UHFFFAOYSA-N 5-(trifluoromethyl)-1,3-dihydrobenzimidazole-2-thione Chemical compound FC(F)(F)C1=CC=C2NC(=S)NC2=C1 HHZOBJBWXJSCSN-UHFFFAOYSA-N 0.000 description 2
- OAXJXWCTAVMKGV-UHFFFAOYSA-N 6-fluoro-2-[(4-methoxy-3-methylpyridin-2-yl)methylsulfanyl]-1h-benzimidazole Chemical compound COC1=CC=NC(CSC=2NC3=CC(F)=CC=C3N=2)=C1C OAXJXWCTAVMKGV-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000000767 anti-ulcer Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
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- BLTAPEIEHGWKKN-UHFFFAOYSA-N methanesulfonate;pyridin-1-ium Chemical compound CS(O)(=O)=O.C1=CC=NC=C1 BLTAPEIEHGWKKN-UHFFFAOYSA-N 0.000 description 2
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- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
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- IAPBORFTCNAJAS-UHFFFAOYSA-N 2-[(4-ethoxy-3-methylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound CCOC1=CC=NC(CS(=O)C=2NC3=CC(=CC=C3N=2)C(F)(F)F)=C1C IAPBORFTCNAJAS-UHFFFAOYSA-N 0.000 description 1
- YXLVOYPWAFRNML-UHFFFAOYSA-N 2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-6-(trifluoromethyl)-1h-benzimidazole Chemical compound COC1=C(C)C=NC(CS(=O)C=2NC3=CC(=CC=C3N=2)C(F)(F)F)=C1C YXLVOYPWAFRNML-UHFFFAOYSA-N 0.000 description 1
- BIXZYNSGMNAXEV-UHFFFAOYSA-M 2-[2-[(2-chloro-2-methylpropyl)sulfanylmethyl]-4-methoxy-3-methylpyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;chloride Chemical compound [Cl-].CC(Cl)(C)CSCC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 BIXZYNSGMNAXEV-UHFFFAOYSA-M 0.000 description 1
- LIYDAEUVOVKTDH-UHFFFAOYSA-M 2-[4-ethoxy-2-[(2-ethoxy-2-methylpropyl)sulfanylmethyl]pyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;chloride Chemical compound [Cl-].CCOC(C)(C)CSCC1=CC(OCC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 LIYDAEUVOVKTDH-UHFFFAOYSA-M 0.000 description 1
- YZTQPPHAQZIFHL-UHFFFAOYSA-M 2-[4-methoxy-3-methyl-2-(2-methyl-2-propan-2-yloxypropyl)pyridin-1-ium-1-yl]-6-(trifluoromethyl)-1h-benzimidazole;chloride Chemical compound [Cl-].CC(C)OC(C)(C)CC1=C(C)C(OC)=CC=[N+]1C1=NC2=CC=C(C(F)(F)F)C=C2N1 YZTQPPHAQZIFHL-UHFFFAOYSA-M 0.000 description 1
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- AFDOMGKBKBKUHB-UHFFFAOYSA-N 5,6-dichloro-1,3-dihydrobenzimidazole-2-thione Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC(=S)N2 AFDOMGKBKBKUHB-UHFFFAOYSA-N 0.000 description 1
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- 241000699670 Mus sp. Species 0.000 description 1
- YBCJDBBYBFMVEG-UHFFFAOYSA-N Ro 18-5364 Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC4=C(C(C(=O)C4(C)C)(C)C)C=C3N=2)=C1C YBCJDBBYBFMVEG-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000002599 gastric fundus Anatomy 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000011256 inorganic filler Substances 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003350 kerosene Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012766 organic filler Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 230000028327 secretion Effects 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 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 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
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- JLGLQAWTXXGVEM-UHFFFAOYSA-N triethylene glycol monomethyl ether Chemical compound COCCOCCOCCO JLGLQAWTXXGVEM-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pulleys (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH290687 | 1987-07-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO883339D0 NO883339D0 (no) | 1988-07-28 |
| NO883339L true NO883339L (no) | 1989-01-30 |
Family
ID=4244272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO88883339A NO883339L (no) | 1987-07-29 | 1988-07-28 | Fremgangsmaate for fremstilling av benzimidazol-2-yl-pyridiniumforbindelser. |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4950677A (fr) |
| EP (1) | EP0304624A3 (fr) |
| JP (1) | JPS6461477A (fr) |
| KR (1) | KR890002113A (fr) |
| AU (1) | AU1979988A (fr) |
| DK (1) | DK405988A (fr) |
| FI (1) | FI883555A (fr) |
| HU (1) | HU200453B (fr) |
| IL (1) | IL87209A0 (fr) |
| MC (1) | MC1962A1 (fr) |
| NO (1) | NO883339L (fr) |
| PT (1) | PT88140A (fr) |
| YU (1) | YU146288A (fr) |
| ZA (1) | ZA885366B (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162317A (en) * | 1988-05-12 | 1992-11-10 | Esai Co., Ltd. | Pyridinium salt and pharmacological composition containing the same |
| WO1992009595A1 (fr) * | 1990-11-29 | 1992-06-11 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Bisulfures nouveaux et connus et leur utilisation |
| GB9413724D0 (en) * | 1994-07-07 | 1994-08-24 | Wellcome Found | Therapeutic nucleosides |
| GB9600143D0 (en) | 1996-01-05 | 1996-03-06 | Wellcome Found | Therapeutic compounds |
| DE69819695D1 (en) | 1997-02-13 | 2003-12-18 | Glaxo Group Ltd | Benzimidazolderivate |
| DK0994890T3 (da) | 1997-06-10 | 2003-12-01 | Univ Michigan | Benzimidazolderivater |
| NZ502882A (en) | 1997-07-30 | 2002-02-01 | Glaxo Group Ltd | Lyxofuranosyl benzimidazoles as antiviral agents |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1476568A (fr) * | 1965-09-07 | 1967-04-14 | Chimetron Sarl | Benzimidazolylpyridiniums et composés apparentés |
| SE8405588D0 (sv) * | 1984-11-08 | 1984-11-08 | Haessle Ab | New compounds |
| DK337086A (da) * | 1985-08-12 | 1987-02-13 | Hoffmann La Roche | Benzimidazolderivater |
-
1988
- 1988-07-20 EP EP88111717A patent/EP0304624A3/fr not_active Withdrawn
- 1988-07-20 DK DK405988A patent/DK405988A/da not_active Application Discontinuation
- 1988-07-21 US US07/222,593 patent/US4950677A/en not_active Expired - Fee Related
- 1988-07-22 ZA ZA885366A patent/ZA885366B/xx unknown
- 1988-07-25 MC MC881995A patent/MC1962A1/fr unknown
- 1988-07-25 HU HU883894A patent/HU200453B/hu not_active IP Right Cessation
- 1988-07-25 AU AU19799/88A patent/AU1979988A/en not_active Abandoned
- 1988-07-25 IL IL87209A patent/IL87209A0/xx unknown
- 1988-07-28 PT PT88140A patent/PT88140A/pt unknown
- 1988-07-28 KR KR1019880009518A patent/KR890002113A/ko not_active Application Discontinuation
- 1988-07-28 NO NO88883339A patent/NO883339L/no unknown
- 1988-07-28 FI FI883555A patent/FI883555A/fi not_active Application Discontinuation
- 1988-07-28 JP JP63189550A patent/JPS6461477A/ja active Pending
- 1988-07-29 YU YU01462/88A patent/YU146288A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HU200453B (en) | 1990-06-28 |
| ZA885366B (en) | 1989-03-29 |
| IL87209A0 (en) | 1988-12-30 |
| KR890002113A (ko) | 1989-04-07 |
| US4950677A (en) | 1990-08-21 |
| PT88140A (pt) | 1990-06-29 |
| DK405988D0 (da) | 1988-07-20 |
| MC1962A1 (fr) | 1989-06-30 |
| AU1979988A (en) | 1989-02-02 |
| YU146288A (en) | 1990-10-31 |
| FI883555A (fi) | 1989-01-30 |
| NO883339D0 (no) | 1988-07-28 |
| DK405988A (da) | 1989-01-30 |
| EP0304624A3 (fr) | 1989-03-22 |
| JPS6461477A (en) | 1989-03-08 |
| FI883555A0 (fi) | 1988-07-28 |
| HUT47926A (en) | 1989-04-28 |
| EP0304624A2 (fr) | 1989-03-01 |
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