FI60002C - Foerfarande foer framstaellning av terapeutiskt anvaendbara 7-acetyl- eller (1-hydroxietyl)-alfa-(tert -butylaminometyl)-2-bensofuranmetanoler - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara 7-acetyl- eller (1-hydroxietyl)-alfa-(tert -butylaminometyl)-2-bensofuranmetanoler Download PDFInfo
- Publication number
- FI60002C FI60002C FI752640A FI752640A FI60002C FI 60002 C FI60002 C FI 60002C FI 752640 A FI752640 A FI 752640A FI 752640 A FI752640 A FI 752640A FI 60002 C FI60002 C FI 60002C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- tert
- compound
- butylaminomethyl
- acetyl
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 14
- 230000001225 therapeutic effect Effects 0.000 title 2
- GNUNYNPODLBKRH-UHFFFAOYSA-N [3-[(tert-butylamino)methyl]-2-benzofuran-1-yl]methanol Chemical compound C(C)(C)(C)NCC=1OC(=C2C=1C=CC=C2)CO GNUNYNPODLBKRH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 38
- -1 hydroxymethylene Chemical group 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 9
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Chemical group 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052804 chromium Inorganic materials 0.000 claims description 2
- 239000011651 chromium Substances 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000012267 brine Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000004217 heart function Effects 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 229940117975 chromium trioxide Drugs 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 125000005283 haloketone group Chemical group 0.000 description 3
- 229960001317 isoprenaline Drugs 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OKMLQUQVVGXQDB-UHFFFAOYSA-N 1-(2-acetyl-1-benzofuran-7-yl)ethyl acetate Chemical compound CC(=O)OC(C)C1=CC=CC2=C1OC(C(C)=O)=C2 OKMLQUQVVGXQDB-UHFFFAOYSA-N 0.000 description 2
- JTUMBVQDEFOAHR-UHFFFAOYSA-N 1-(7-ethyl-1-benzofuran-2-yl)ethanone Chemical compound CCC1=CC=CC2=C1OC(C(C)=O)=C2 JTUMBVQDEFOAHR-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- IVGOVTHRNPDBAZ-UHFFFAOYSA-N 7-ethyl-2-(2-methyl-1,3-dioxolan-2-yl)-1-benzofuran Chemical compound O1C=2C(CC)=CC=CC=2C=C1C1(C)OCCO1 IVGOVTHRNPDBAZ-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 2
- PPNZFWQOMJVVJT-UHFFFAOYSA-N 1-(5-bromo-7-ethyl-1-benzofuran-2-yl)ethanone Chemical compound CCC1=CC(Br)=CC2=C1OC(C(C)=O)=C2 PPNZFWQOMJVVJT-UHFFFAOYSA-N 0.000 description 1
- LXIFFWMQXXDZHH-UHFFFAOYSA-N 1-[2-(2-bromoacetyl)-1-benzofuran-7-yl]ethyl acetate Chemical compound CC(=O)OC(C)C1=CC=CC2=C1OC(C(=O)CBr)=C2 LXIFFWMQXXDZHH-UHFFFAOYSA-N 0.000 description 1
- UBOQDOBPGFVUFT-UHFFFAOYSA-N 1-[2-(2-methyl-1,3-dioxolan-2-yl)-1-benzofuran-7-yl]ethyl acetate Chemical compound O1C=2C(C(OC(C)=O)C)=CC=CC=2C=C1C1(C)OCCO1 UBOQDOBPGFVUFT-UHFFFAOYSA-N 0.000 description 1
- PUBOIWZVVYEPIM-UHFFFAOYSA-N 2-(tert-butylamino)-1-[7-(1-hydroxyethyl)-2-benzofuran-1-yl]ethanol Chemical compound CC(O)C1=CC=CC2=COC(C(O)CNC(C)(C)C)=C12 PUBOIWZVVYEPIM-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
- WFIWAAWXIAUFAF-UHFFFAOYSA-N 7-ethyl-1-benzofuran Chemical compound CCC1=CC=CC2=C1OC=C2 WFIWAAWXIAUFAF-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- AXWQJUBSRGTJBA-UHFFFAOYSA-N CC(=O)C1=CC=CC2=C(OC(=C21)CO)CNC(C)(C)C Chemical compound CC(=O)C1=CC=CC2=C(OC(=C21)CO)CNC(C)(C)C AXWQJUBSRGTJBA-UHFFFAOYSA-N 0.000 description 1
- RXFMDJXPBRZYAG-UHFFFAOYSA-N CC(C)(C)NCC1=C2C=CC=CC2=C(O1)COC(=O)C(=O)O Chemical compound CC(C)(C)NCC1=C2C=CC=CC2=C(O1)COC(=O)C(=O)O RXFMDJXPBRZYAG-UHFFFAOYSA-N 0.000 description 1
- KJZXSUQNGFVGLG-UHFFFAOYSA-N CC(O)OC1=CC=CC2=C(OC(=C21)CNC(C)(C)C)CO Chemical compound CC(O)OC1=CC=CC2=C(OC(=C21)CNC(C)(C)C)CO KJZXSUQNGFVGLG-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001907 coumarones Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000003944 halohydrins Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 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
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- GNMJFQWRASXXMS-UHFFFAOYSA-M trimethyl(phenyl)azanium;bromide Chemical compound [Br-].C[N+](C)(C)C1=CC=CC=C1 GNMJFQWRASXXMS-UHFFFAOYSA-M 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4189074 | 1974-09-26 | ||
| GB4189074A GB1472959A (en) | 1974-09-26 | 1974-09-26 | Benzofuran derivatives and a process for the manufacture thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI752640A7 FI752640A7 (en, 2012) | 1976-03-27 |
| FI60002B FI60002B (fi) | 1981-07-31 |
| FI60002C true FI60002C (fi) | 1981-11-10 |
Family
ID=10421827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI752640A FI60002C (fi) | 1974-09-26 | 1975-09-22 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 7-acetyl- eller (1-hydroxietyl)-alfa-(tert -butylaminometyl)-2-bensofuranmetanoler |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US3972900A (en, 2012) |
| JP (1) | JPS604177B2 (en, 2012) |
| AR (2) | AR208714A1 (en, 2012) |
| AT (1) | AT349003B (en, 2012) |
| BE (1) | BE833785A (en, 2012) |
| CA (1) | CA1059525A (en, 2012) |
| CH (3) | CH612960A5 (en, 2012) |
| DD (1) | DD122521A5 (en, 2012) |
| DE (1) | DE2542611C2 (en, 2012) |
| DK (1) | DK136529B (en, 2012) |
| ES (1) | ES441266A1 (en, 2012) |
| FI (1) | FI60002C (en, 2012) |
| FR (1) | FR2285870A1 (en, 2012) |
| GB (1) | GB1472959A (en, 2012) |
| IE (1) | IE41850B1 (en, 2012) |
| IL (1) | IL48063A (en, 2012) |
| LU (1) | LU73453A1 (en, 2012) |
| NL (1) | NL7511363A (en, 2012) |
| NO (1) | NO144039C (en, 2012) |
| PH (2) | PH11562A (en, 2012) |
| SE (1) | SE422326B (en, 2012) |
| ZA (1) | ZA755635B (en, 2012) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4238487A (en) * | 1979-10-31 | 1980-12-09 | Merck & Co., Inc. | Aminoalkyl benzofuran derivatives |
| CA1175851A (en) * | 1980-09-26 | 1984-10-09 | Beecham Group Limited | Secondary amines |
| EP0076973B1 (en) * | 1981-10-02 | 1986-04-02 | Investigacion Tecnica y Aplicada, S.A. | A new dioxolanic compound and its method of preparation; a new dioxolanic amine with pharmacological activity, its method of preparation, and the pharmaceutical compositions containing them |
| US4495199A (en) * | 1982-09-30 | 1985-01-22 | Ribalta Jose Miguel B | Dioxolanic amine with pharmacological activity, its method of preparation, the pharmaceutical compositions containing same and their use in human medicine |
| US4851554A (en) * | 1987-04-06 | 1989-07-25 | University Of Tennessee Research Corporation | Certain 3-substituted 2-alkyl benzofuran derivatives |
| US4806663A (en) * | 1987-04-06 | 1989-02-21 | The University Of Tennessee Research Corporation | Certain 3-substituted 2-alkyl benzofuran derivatives |
| US4831156A (en) * | 1987-09-30 | 1989-05-16 | The University Of Tennessee Research Corp. | 3-substituted 2-alkyl indole derivatives |
| JPH0622398U (ja) * | 1992-08-21 | 1994-03-22 | 東京製綱株式会社 | 低伸度ワイヤロープ |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1058822A (en) * | 1963-07-30 | 1967-02-15 | Ici Ltd | 3-amino-2-hydroxypropoxy heterocyclic derivatives |
-
1974
- 1974-09-26 GB GB4189074A patent/GB1472959A/en not_active Expired
-
1975
- 1975-09-03 ZA ZA00755635A patent/ZA755635B/xx unknown
- 1975-09-04 CH CH1145675A patent/CH612960A5/xx not_active IP Right Cessation
- 1975-09-04 CH CH195279A patent/CH614438A5/xx not_active IP Right Cessation
- 1975-09-04 CH CH195179A patent/CH614437A5/xx not_active IP Right Cessation
- 1975-09-05 IL IL48063A patent/IL48063A/xx unknown
- 1975-09-15 US US05/613,687 patent/US3972900A/en not_active Expired - Lifetime
- 1975-09-17 CA CA235,651A patent/CA1059525A/en not_active Expired
- 1975-09-22 FI FI752640A patent/FI60002C/fi not_active IP Right Cessation
- 1975-09-23 AR AR260491A patent/AR208714A1/es active
- 1975-09-23 SE SE7510671A patent/SE422326B/xx unknown
- 1975-09-24 FR FR7529227A patent/FR2285870A1/fr active Granted
- 1975-09-24 LU LU73453A patent/LU73453A1/xx unknown
- 1975-09-24 DE DE2542611A patent/DE2542611C2/de not_active Expired
- 1975-09-25 ES ES441266A patent/ES441266A1/es not_active Expired
- 1975-09-25 NO NO753267A patent/NO144039C/no unknown
- 1975-09-25 BE BE160343A patent/BE833785A/xx not_active IP Right Cessation
- 1975-09-25 AT AT734675A patent/AT349003B/de not_active IP Right Cessation
- 1975-09-25 IE IE2097/75A patent/IE41850B1/en unknown
- 1975-09-25 DK DK432275AA patent/DK136529B/da not_active IP Right Cessation
- 1975-09-25 DD DD188563A patent/DD122521A5/xx unknown
- 1975-09-25 PH PH17609A patent/PH11562A/en unknown
- 1975-09-25 JP JP50114965A patent/JPS604177B2/ja not_active Expired
- 1975-09-26 NL NL7511363A patent/NL7511363A/xx not_active Application Discontinuation
-
1976
- 1976-06-25 AR AR263745A patent/AR211929A1/es active
-
1977
- 1977-03-22 PH PH19576A patent/PH18198A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2244967T3 (es) | Nuevas hidroxipiridinonas. | |
| CH655102A5 (de) | N-imidazolylderivate von bicyclischen verbindungen, verfahren zu deren herstellung und arzneimittel, welche diese enthalten. | |
| PT86459B (pt) | Processo para a preparacao de derivados de cumarano substituidos naposicao 3 | |
| FI60002C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 7-acetyl- eller (1-hydroxietyl)-alfa-(tert -butylaminometyl)-2-bensofuranmetanoler | |
| EP0253711A1 (fr) | Nouveaux dérivés du 1H,3H-Pyrrolo [1,2-c] thiazole, leur préparation et les Compositions pharmaceutiques qui les contiennent | |
| WO1994010157A1 (en) | Styrene derivative and salts thereof | |
| FR2644456A1 (fr) | Nouveaux derives du 1h, 3h-pyrrolo(1,2-c)thiazolecarboxamide-7, leur preparation et les compositions pharmaceutiques qui les contiennent | |
| SU1151209A3 (ru) | Способ получени @ -токофериловых эфиров 5-замещенной пиколиновой кислоты | |
| KR100281867B1 (ko) | 3-(비스-치환페닐메틸렌)옥신돌유도체 | |
| FR2521992A1 (fr) | Nouveaux composes de pyridine utiles comme medicaments | |
| JP2980749B2 (ja) | フラン誘導体 | |
| DE2337068A1 (de) | 1-benzylindenylsaeuren | |
| HU211554A9 (en) | Circulation-active dibenzo/1,5/dioxocin-5-ones | |
| US5912262A (en) | Heterocyclic compounds | |
| JPS6191172A (ja) | ２‐ピリジン‐チオール誘導体、その製造方法およびそれを含有する医薬組成物 | |
| EP0228314A2 (en) | Use of ethanol/amine derivatives in treating or preventing hyperlipemia | |
| US4247690A (en) | Lasalocid derivatives | |
| KR790001983B1 (ko) | 벤조푸란 유도체의 제조방법 | |
| FI61871C (fi) | Analogifoerfarande foer framstaellning av antidepressivt verkande trifluormetylsubstituerade aralkylestrar av alanin | |
| US3671636A (en) | Methods for treating hypertension or inhibiting gastric secretion | |
| HU196591B (en) | Process for producing 4-(phenylpropyl)indole derivatives and pharmaceutics comprising these compounds as active ingredient | |
| US4435393A (en) | Derivatives of 10-(1-azabicyclo[2.2.2]oct-3-yl)-N,N dimethyl-10H-phenothiazine-2-sulfonamide as medicaments | |
| FI85465B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 4-fenylpropyl-indolderivat. | |
| US3629285A (en) | Derivatives of 3-hydroxy-alpha-(1-aminoethyl)-benzyl alcohol | |
| JPS61218588A (ja) | インタ−フラニレン−プロスタサイクリン誘導体、その製造法および医薬組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F HOFFMANN-LA ROCHE & CO. AG |