NO782539L - Fremgangsmaate ved fremstilling av prostaglandinantagonistiske forbindelser - Google Patents
Fremgangsmaate ved fremstilling av prostaglandinantagonistiske forbindelserInfo
- Publication number
- NO782539L NO782539L NO782539A NO782539A NO782539L NO 782539 L NO782539 L NO 782539L NO 782539 A NO782539 A NO 782539A NO 782539 A NO782539 A NO 782539A NO 782539 L NO782539 L NO 782539L
- Authority
- NO
- Norway
- Prior art keywords
- thiepine
- acid
- mixture
- carboxylic acid
- dihydro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 54
- 238000000034 method Methods 0.000 title claims description 24
- -1 C-^ - C4 -alkanoyl Chemical group 0.000 claims description 43
- 239000002253 acid Substances 0.000 claims description 42
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 96
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- 239000007787 solid Substances 0.000 description 55
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 50
- 239000000047 product Substances 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 238000002844 melting Methods 0.000 description 42
- 230000008018 melting Effects 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- 229960000583 acetic acid Drugs 0.000 description 31
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 19
- 239000007858 starting material Substances 0.000 description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 14
- 150000003180 prostaglandins Chemical class 0.000 description 13
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 208000006673 asthma Diseases 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 150000003536 tetrazoles Chemical class 0.000 description 11
- 125000005431 alkyl carboxamide group Chemical group 0.000 description 10
- 125000005907 alkyl ester group Chemical group 0.000 description 10
- 229910052500 inorganic mineral Inorganic materials 0.000 description 10
- 235000010755 mineral Nutrition 0.000 description 10
- 239000011707 mineral Substances 0.000 description 10
- YOUSMYQBLMLPTA-UHFFFAOYSA-N 5,6-dihydrobenzo[b][1]benzothiepine-2-carboxylic acid Chemical compound C1CC2=CC=CC=C2SC2=CC(C(=O)O)=CC=C21 YOUSMYQBLMLPTA-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 229910021529 ammonia Inorganic materials 0.000 description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 150000003462 sulfoxides Chemical class 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 8
- 239000000920 calcium hydroxide Substances 0.000 description 8
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 150000003551 thiepines Chemical class 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 150000003457 sulfones Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 239000012954 diazonium Substances 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 150000001451 organic peroxides Chemical class 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- WTURFORPERPPRJ-UHFFFAOYSA-N 2-(3-bromophenyl)sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1SC1=CC=CC(Br)=C1 WTURFORPERPPRJ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- HSEYABVKUOFKTN-UHFFFAOYSA-N 5,6-dihydrobenzo[b][1]benzothiepine-2-carbonitrile Chemical compound C1CC2=CC=CC=C2SC2=CC(C#N)=CC=C21 HSEYABVKUOFKTN-UHFFFAOYSA-N 0.000 description 5
- NZJFJZLLNNMMDF-UHFFFAOYSA-N 5-oxo-6h-benzo[b][1]benzothiepine-2-carbonitrile Chemical compound O=C1CC2=CC=CC=C2SC2=CC(C#N)=CC=C12 NZJFJZLLNNMMDF-UHFFFAOYSA-N 0.000 description 5
- XEZFAXAPRGCYCY-UHFFFAOYSA-N 5-oxo-6h-benzo[b][1]benzothiepine-2-carboxylic acid Chemical compound S1C2=CC=CC=C2CC(=O)C2=CC=C(C(=O)O)C=C12 XEZFAXAPRGCYCY-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- RTZHFJMUQLISHT-UHFFFAOYSA-N benzo[b][1]benzothiepine-2-carbonitrile Chemical compound C1=CC2=CC=CC=C2SC2=CC(C#N)=CC=C21 RTZHFJMUQLISHT-UHFFFAOYSA-N 0.000 description 5
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 5
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- 238000007254 oxidation reaction Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
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- 239000004471 Glycine Substances 0.000 description 4
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- 150000003973 alkyl amines Chemical class 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000012223 aqueous fraction Substances 0.000 description 4
- 230000001851 biosynthetic effect Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- 239000003826 tablet Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
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- NTXOTYBYIXQHGB-UHFFFAOYSA-N 3-hydroxybenzo[b][1]benzothiepine-9-carboxylic acid Chemical compound C1=CC2=CC(O)=CC=C2SC2=CC(C(=O)O)=CC=C21 NTXOTYBYIXQHGB-UHFFFAOYSA-N 0.000 description 3
- RJADSWKTSXTZJF-UHFFFAOYSA-N 5-oxo-6h-benzo[b][1]benzothiepine-2-carbonyl chloride Chemical compound S1C2=CC=CC=C2CC(=O)C2=CC=C(C(=O)Cl)C=C12 RJADSWKTSXTZJF-UHFFFAOYSA-N 0.000 description 3
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
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- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- 239000005708 Sodium hypochlorite Substances 0.000 description 3
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- KMAWVRYYKYVCNR-UHFFFAOYSA-N benzo[b][1]benzothiepine Chemical class C1=CC2=CC=CC=C2SC2=CC=CC=C21 KMAWVRYYKYVCNR-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
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- 238000001035 drying Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
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- 238000001953 recrystallisation Methods 0.000 description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81919977A | 1977-07-26 | 1977-07-26 | |
| US91721278A | 1978-06-23 | 1978-06-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO782539L true NO782539L (no) | 1979-01-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO782539A NO782539L (no) | 1977-07-26 | 1978-07-24 | Fremgangsmaate ved fremstilling av prostaglandinantagonistiske forbindelser |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0011067B1 (fi) |
| JP (1) | JPS5444691A (fi) |
| AR (2) | AR226527A1 (fi) |
| AU (1) | AU517813B2 (fi) |
| CA (1) | CA1128048A (fi) |
| DD (1) | DD140746A5 (fi) |
| DE (1) | DE2861754D1 (fi) |
| DK (1) | DK330578A (fi) |
| ES (5) | ES471871A1 (fi) |
| FI (1) | FI782323A (fi) |
| GR (1) | GR67276B (fi) |
| IE (1) | IE47553B1 (fi) |
| IT (1) | IT1107485B (fi) |
| NO (1) | NO782539L (fi) |
| PL (3) | PL117756B1 (fi) |
| PT (1) | PT68303A (fi) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4536507A (en) * | 1977-07-26 | 1985-08-20 | Merck & Co., Inc. | Prostaglandin antagonists |
| PT71280B (en) * | 1979-06-01 | 1981-09-17 | Merck & Co Inc | Process for preparing prostaglandin antagonists |
| US4237160A (en) * | 1979-11-27 | 1980-12-02 | Merck Sharp & Dohme (I.A.) Corp. | 3-Hydroxymethyldibenzo[b,f]thiepins as prostaglandin antagonists |
| EP0029587B1 (en) * | 1979-11-27 | 1984-06-13 | Merck Sharp & Dohme (I.A.) Corp. | 3-hydroxymethyldibenzo(b,f)thiepins and dibenzo(b,f)thiepin-3-carboxaldehydes as prostaglandin antagonists, process for their preparation and pharmaceutical compositions |
| NO811187L (no) * | 1980-11-24 | 1982-05-25 | Merck & Co Inc | Fremgangsmaate ved fremstilling av 7-fluor-dibenzo-(b,f)-thiepinderivater |
| US4535171A (en) * | 1982-11-18 | 1985-08-13 | Merck Frosst Canada, Inc. | Dibenzo[b,f]thiepin-3-carboxaldehydes as prostaglandin antagonists |
| US4622403A (en) * | 1983-10-11 | 1986-11-11 | Merck Frosst Canada, Inc. | 6-H dibenz[b,f]thiepin compounds |
| US4663347A (en) | 1983-10-31 | 1987-05-05 | Merck Frosst Canada, Inc. | Benzofuran 2-carboxylic acid esters useful as inhibitors of leukotriene biosynthesis |
| CA1309557C (en) | 1985-06-18 | 1992-10-27 | Robert N. Young | Leukotriene antagonists |
| DE3786030T2 (de) | 1986-03-27 | 1993-12-02 | Merck Frosst Canada Inc | Tetrahydrocarbazole Ester. |
| EP0480716A1 (en) | 1990-10-12 | 1992-04-15 | Merck Frosst Canada Inc. | Saturated hydroxyalkylquinoline acids as leukotriene antagonists |
| US5410054A (en) * | 1993-07-20 | 1995-04-25 | Merck Frosst Canada, Inc. | Heteroaryl quinolines as inhibitors of leukotriene biosynthesis |
| EP0885610A4 (en) * | 1996-01-19 | 1999-04-21 | Nippon Suisan Kaisha Ltd | RELAXING SMOOTH MUSCLES OF THE TRACHEA |
| PL352840A1 (en) | 1999-06-03 | 2003-09-08 | Nippon Suisan Kaisha, Ltd. | Tricyclic fused heterocycle compounds, process for preparing the same and use thereof |
| TWI275495B (en) * | 2004-09-21 | 2007-03-11 | Sony Corp | Printer and printing method |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4101667A (en) * | 1975-05-30 | 1978-07-18 | Nippon Chemiphar Co., Ltd. | Benzo[b,f]thiepin derivatives |
| JPS5346989A (en) * | 1976-10-06 | 1978-04-27 | Nippon Chemiphar Co Ltd | Novel dibenzo(b,f)thiepin derivatives and their preparation |
| JPS6021156B2 (ja) * | 1976-12-03 | 1985-05-25 | 日本ケミフア株式会社 | ベンゾチエピン誘導体およびその製法 |
-
1978
- 1978-07-17 PT PT68303A patent/PT68303A/pt unknown
- 1978-07-19 GR GR56820A patent/GR67276B/el unknown
- 1978-07-19 AU AU38177/78A patent/AU517813B2/en not_active Expired
- 1978-07-19 IT IT50375/78A patent/IT1107485B/it active
- 1978-07-19 ES ES471871A patent/ES471871A1/es not_active Expired
- 1978-07-21 DE DE7878300183T patent/DE2861754D1/de not_active Expired
- 1978-07-21 AR AR273031A patent/AR226527A1/es active
- 1978-07-21 EP EP78300183A patent/EP0011067B1/en not_active Expired
- 1978-07-24 NO NO782539A patent/NO782539L/no unknown
- 1978-07-25 CA CA308,068A patent/CA1128048A/en not_active Expired
- 1978-07-25 DK DK330578A patent/DK330578A/da not_active Application Discontinuation
- 1978-07-25 DD DD78206923A patent/DD140746A5/de unknown
- 1978-07-25 IE IE1488/78A patent/IE47553B1/en unknown
- 1978-07-25 FI FI782323A patent/FI782323A/fi not_active Application Discontinuation
- 1978-07-26 PL PL1978219619A patent/PL117756B1/pl unknown
- 1978-07-26 PL PL1978208653A patent/PL116355B1/pl unknown
- 1978-07-26 JP JP9054978A patent/JPS5444691A/ja active Granted
- 1978-07-26 PL PL1978225727A patent/PL120813B1/pl unknown
-
1979
- 1979-04-02 ES ES479217A patent/ES479217A1/es not_active Expired
- 1979-04-02 ES ES479216A patent/ES479216A1/es not_active Expired
- 1979-04-02 ES ES479218A patent/ES479218A1/es not_active Expired
- 1979-04-02 ES ES479215A patent/ES479215A1/es not_active Expired
- 1979-09-20 AR AR278140A patent/AR222666A1/es active
Also Published As
| Publication number | Publication date |
|---|---|
| PL117756B1 (en) | 1981-08-31 |
| DD140746A5 (de) | 1980-03-26 |
| DK330578A (da) | 1979-01-27 |
| ES479215A1 (es) | 1979-07-01 |
| AU517813B2 (en) | 1981-08-27 |
| AR222666A1 (es) | 1981-06-15 |
| ES471871A1 (es) | 1979-10-01 |
| IE781488L (en) | 1979-01-26 |
| GR67276B (fi) | 1981-06-26 |
| AU3817778A (en) | 1980-01-24 |
| PL120813B1 (en) | 1982-03-31 |
| ES479216A1 (es) | 1979-07-01 |
| ES479217A1 (es) | 1979-07-01 |
| EP0011067A1 (en) | 1980-05-28 |
| PL208653A1 (pl) | 1979-06-04 |
| IT7850375A0 (it) | 1978-07-19 |
| EP0011067B1 (en) | 1982-04-21 |
| IE47553B1 (en) | 1984-04-18 |
| JPS5444691A (en) | 1979-04-09 |
| JPS6250470B2 (fi) | 1987-10-24 |
| AR226527A1 (es) | 1982-07-30 |
| CA1128048A (en) | 1982-07-20 |
| IT1107485B (it) | 1985-11-25 |
| ES479218A1 (es) | 1979-11-01 |
| PT68303A (en) | 1978-08-01 |
| FI782323A (fi) | 1979-01-27 |
| DE2861754D1 (en) | 1982-06-03 |
| PL116355B1 (en) | 1981-06-30 |
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