NO119801B - - Google Patents
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- Publication number
- NO119801B NO119801B NO167741A NO16774167A NO119801B NO 119801 B NO119801 B NO 119801B NO 167741 A NO167741 A NO 167741A NO 16774167 A NO16774167 A NO 16774167A NO 119801 B NO119801 B NO 119801B
- Authority
- NO
- Norway
- Prior art keywords
- amino
- radical
- phenyl
- trifluoromethylphenyl
- ethyl
- Prior art date
Links
- -1 hydroxyl- Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 9
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 150000007513 acids Chemical class 0.000 claims description 5
- 208000022531 anorexia Diseases 0.000 claims description 4
- 206010061428 decreased appetite Diseases 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- LSPHULWDVZXLIL-LDWIPMOCSA-N (?)-Camphoric acid Chemical compound CC1(C)[C@@H](C(O)=O)CC[C@@]1(C)C(O)=O LSPHULWDVZXLIL-LDWIPMOCSA-N 0.000 claims description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000001294 propane Substances 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- KWTSXDURSIMDCE-UHFFFAOYSA-N 1-phenylpropan-2-amine Chemical compound CC(N)CC1=CC=CC=C1 KWTSXDURSIMDCE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
- MLBHFBKZUPLWBD-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]-2-propanamine Chemical compound CC(N)CC1=CC=CC(C(F)(F)F)=C1 MLBHFBKZUPLWBD-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- NOYKUYNVZHTPCI-UHFFFAOYSA-N 1-phenylcyclopentane-1-carbonyl chloride Chemical compound C=1C=CC=CC=1C1(C(=O)Cl)CCCC1 NOYKUYNVZHTPCI-UHFFFAOYSA-N 0.000 description 1
- VRBVHQUSAOKVDH-UHFFFAOYSA-N 2-(4-chlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1 VRBVHQUSAOKVDH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- CUSDKBHKWFSTTH-UHFFFAOYSA-N 2-[4-(2-methylpropyl)phenyl]acetyl chloride Chemical compound CC(C)CC1=CC=C(CC(Cl)=O)C=C1 CUSDKBHKWFSTTH-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- DVIHKVWYFXLBEM-UHFFFAOYSA-N 2-hydroxybenzoyl chloride Chemical compound OC1=CC=CC=C1C(Cl)=O DVIHKVWYFXLBEM-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- QGXMHCMPIAYMGT-UHFFFAOYSA-N 2-phenylbutanoyl chloride Chemical compound CCC(C(Cl)=O)C1=CC=CC=C1 QGXMHCMPIAYMGT-UHFFFAOYSA-N 0.000 description 1
- FOTITZRWZUAVPH-UHFFFAOYSA-N 2-phenylpropanoyl chloride Chemical compound ClC(=O)C(C)C1=CC=CC=C1 FOTITZRWZUAVPH-UHFFFAOYSA-N 0.000 description 1
- RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000001953 Hypotension 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
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- CPYJFDPRIHGAKB-UHFFFAOYSA-N N-propan-2-yl-N-(trifluoromethyl)aniline Chemical compound CC(C)N(C(F)(F)F)C1=CC=CC=C1 CPYJFDPRIHGAKB-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002908 adrenolytic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CJAVTWRYCDNHSM-UHFFFAOYSA-N benzoic acid 2-[1-[3-(trifluoromethyl)phenyl]propan-2-ylamino]ethyl ester Chemical compound C=1C=CC=CC=1C(=O)OCCNC(C)CC1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension 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
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/08—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Fremgangsmåte for fremstilling av nye derivater av l-fenyl-2-aminopropan for anvendelse som anorexia.
Nærværende oppfinnelse vedrorer en fremgangsmåte for fremstilling av nye trifluormetylderivater av 1-fenyl-2-aminopropan for anvendelse som anorexia og med den generelle formel I:
hvor R' betegner et hydrogenatom eller en COR"-gruppe, i hvilken R" betegner et alkylradikal med inntil 6 karbonatomer som kan
være substituert med et halogenatom, et karboksyl-, fenyl-, (lavere alkyl)fenyl- eller halogenfenoksyradikal,
et cykloalkylradikal med 3-7 karbonatomer som kan være substituert med et fenylradikal,
et alkenylradikal med 2-6 karbonatomer som kan være substituert med et fenylradikal eller et trifluormetylfenylradikal,
et fenylradikal som kan være substituert med et halogenatom, et hydroksyl-, metylendioksy-, nitro-, amino-, trifluormetyl- eller fenylradikal eller med et eller to lavere alkylradikaler med opp til k karbonatomer,
i form av racemiske blandinger eller optiske isomerer eller i form av addisjonssalter med mineralsyrer eller organiske syrer, og fremgangsmåten karakteriseres ved at man omsetter et tri-fluormetylfenyl-isopropylamin med den generelle formel II:
med etylenoksyd med den generelle formel IV:
og at de på denne måte oppnådde forbindelser eventuelt forestres med et funksjonelt derivat av syren R"C00H hvor R" har foran angitte betydning og, hvis onsket, reduseres en nitrogruppe til en aminogruppe under trykk og ved hjelp av en katalysator og, hvis onsket, spaltes de racemiske blandinger med d (-) dibenzoyl-
vinsyre"for å oppnå venstrédreiéndé is6merér"og~deretter med" d-kamfersyre for å oppnå de tilsvarende hijyredreiende isomerer.
i l-fenyl-2-aminopropaner for terapeutisk bruk er tidligere kjent, og i fransk patent nr. 1 219 25<*>f er slike terapeutisk aktive derivater av l-fenyl-2-aminopropaner beskrevet med hypotensive, spasj molytiskeog adrenolytiske egenskaper. De etter nærværende: oppfin-j-neise fremstilte derivater av l-fenyl-2-aminopropan er imidlertid anvendelige som anorexia. |
Fremstillingen av addisjonssalter av de nye forbindelser med den, generelle formel I med mineralsyrer og organiske syrer omfattes<:>også av oppfinnelsen* Som syrer som anvendes ved dannelsen av disse addisjonssalter, kan nevnes mineralsyrer: hydrogenklorid, hydro-j genbromid, metansulfonsyre, svovelsyre, fosforsyre, sulfaminsyrei og organiske syrer: eddiksyre, propionsyre,. maleinsyre, fumarsyrf, vinsyre, sitronsyre, oxalsyre, benzoesyre, antranilsyre m.m.
De nye derivater og deres fysiologisk virksomme salter kan anvendes til å nedsette appetitten.
Deres toksisitet er lav, og deres DL ^-verdier bestemt på mus varierer mellom 92 og 312 mg/kg intraperitonealt, og mellom 750 og 2000 ug/kg oralt.
Den appetittmin3kede virkning ble undersakt på rotter og hunder.\ Det ble funnet at den aktive dose som 2 timer etter administreringen; av produktene minsket matlysten med 50% hos dyr, ligger mellom j og 20 mg/kg oralt. I
i De farmakologiske data for fremstilte derivater og et referanse-i produkt vil fremgå av den på slutten av denne beskrivelse gjen- i gitteitabellariske oversikt. j
i Kidlene kan administreres pasientene i forskjellige farmasøytiske former, som f.eks. tabletter, piller, granulater, kapsler, avfbr-lngspiller eller som vasker som kan drikkes eller innsprbytes, i forbindelse med vanlige farmasøytiske faste eller flytende tjære-stoffer f.eks. destillert vann, laktose, talkum, gummi arabicum nagnesiumsterarat, etylcellulose. De anvendte doser kan variere!
i fra 10 til 200 mg ved oral, rektal eller parenteral administrering.
De folgende eksempler illustrerer fremgangsmåten ifolge oppfinnelsen. Alle deler er vektdeler, dersom intet annet er angitt, og smeltepunktene ble bestemt ved hjelp av Kofler-
metoden.
EKSEMPEL 1
l-(m-t-rifluormetylfenyl) -2- ["((-(-hydroksy-etyl )amino] -propan
I en 1 liters autoklav innfores ved en temperatur på 20°C
305 deler 1-(m-trifluormetylfenyl)-2-amino-propan, 53 deler etylenoksyd og 37?5deler vann. Man lar deretter blandingen oppvarmes til romtemperatur, rorer om i 1 time ved denne
temperatur og oppvarmer deretter reaksjonsblandingen til 100-
110°C og opprettholder denne temperatur i k timer.
Destillasjon av råproduktet gir 15<*>+ deler 1-(m-trifluormetyl-fenyl)-2- [ ((l-hydroksyetyl)-amino] -propan, kp/Q^mm - 109 -
111°C, hvis sure fumarat smelter ved 133°C (isopropanol).
EKSEMPEL 2
1-1- (m-trif luormetylf enyl) -2- [ (|-5-hydroksy-etyl) -amino] -propan
Man tilsetter 75 deler dl 1-(m-trifluormetylfenyl)-2-[(^-hydroksy-etyl)-amino] -propan til en opplosning av lhr/ deler d (-)-dibenzoyl-vinsyre i l800 deler etylacetat under tilbake-
lop og ornroring. Etter avkjoling til romtemperatur, filtreres saltet, vaskes med etylacetat og torkes. Det erholdes 95 deler av salt A som ornkrystallisert to ganger i etanol gir 65 deler rent salt (smp. 15<1>+°C).
Basen frigjbres fra saltet A ved tilsetting av en vandig opp-
losning av natriumhydroksyd, etterfulgt av en ekstraksjon med eter og torking med MgSO^. Det oppnås 23,5 deler l-l-(m-tri-fluormetylf enyl)-2-[((3-hydroksy-etyl)-amino] -propan, kp/n =
or22 o j'
109 C, [a] D -13,7 (C.16 j etanol), hvis fumarat smelter
ved 135°C (isopropanol).
EKSEMPEL 3
d-1- (m-trif luormetylf enyl) -2- ["([^-hydroksy-etyl) -amino] -propan
Filtratet etter separeringen av saltet A i eks. 2 konsentreres under vakuum og basen frigjores. Det erholdes 2k- deler av basen,<kp/>]_ ?^?lmm<=><1>11-115°C, [a]^2,5=+6^o (c<l6 . etanol). 25 deler av denne base behandles med 22 deler d-kamfersyre i 80 deler etylacetat. Når krystalliseringen er avsluttet, filtreres og torkes det således dannede salt B. Det erholdes 18 deler surt d-kamferat, smp. 126°C, som omkrystal-lisert i % deler etylacetat, gir 16 deler rent B-salt, smp.
127°C
Frigjøringen av basen fra dette salt B med en vandig opplosning av natriumhydroksyd gir d-1-(m-trif luormetylf enyl)-2- [((3-hydroksy-etyl)-amino]-propan, kp/Q ^ = 111-112 o C, [<x]D 22 'P ^) + I356<0>(C.I6 ; etanol) hvis fumarat smelter ved 135°C (isopropanol).
EKSEMPEL k
1- (m-trifluormetylfenyl)-2- [(fi-acetyloksy-etyl)-amino]-propanhydroklorid.
Til en opplosning av 1^,2 deler 1-(m-trifluormetylfenyl)-
2- [((3-hydroksy-etyl) -amino]-propanhydroklorid i 70 deler etylacetat tilsettes 5jl deler eddiksyreanhydrid. Etter 2 timers tilbakelop kjoles opplosningen og produktet torkes og omkrystalliseres i 70 deler etylacetat. Det erholdes 8,8 deler 1-(m-trifluormetylfenyl)-2- [(g-acetyloksy-etyl)-amino] -propanhydroklorid som smelter ved 136°C.
Ved å arbeide på analog måte fremstilles:
a) 1-(m-trifluormetylfenyl)-2- TO-propionyloksyetyl)-amino]-propanhydroklorid, smp. 135"°C (isopropanol) fra1-(m-trifluor-
| metylfenyl)-2-fO-hydroksy-etyl)-amino]-propan og propionsyre- j anhydrid.
i
b) l-(m-trifluormetylfenyl)-2-[(Ø-succinyloksy-etyl)-amino]-propanhydroklorid, smp. 113°C (etylacetat) fra 1-(«-trifluor-
metylf enyl) -2- [O -hydroksy-etyl) -amino] -propan og ravsyrean- | hydrid. i
EKSEMPEL 5
1- (m-trifluormetylfenyl)-2- CO-salicyloyloksy-etyl)-amino]-propanhydroklorid. j
Til en opplosning av 2^,7 deler l-(m-trlfluormetylfenyl)-2- !
[(Ø-hydroksy-etyl)-amino] -propan i IkO deler vannfri benzen I tilsettes suksessivt 15 deler V,7 N hydrogenklorid i eter og en opplosning av 15»6 deler salicyloylklorid i 2k deler vannfri
benzen. Tilsetningen varer 10 minutter og reaksjonsblandingen oppvarmes deretter under tilbakelOp i 3 timer.
Det faste produkt filtreres og omkrystalliseres i 180 deler etylacetat. Det erholdes 30,5 deler 1-(m-trifluormetylfenyl)-2- C(ø-salicyloyloksy-etyl)-aminoJ-propanhydroklorid som smelter ved lMf°C.
EKSEMPEL 6
1- (m-trifluormetylfenyl)-2- [(Ø-benzoyloksy-etyl)-amino]-propan
Til en opplosning av 2kt7deler l-(m-trlfluormetylfenyl)-2- C(Ø-hydroksy-etyl)-amino]-propan i IkO deler vannfri benzen tilsettes suksessivt 15 deler V,7 N hydrogenklorid i eter og en oppløsning av lk deler benzoylklorid i 2k deler vannfri benzen. Tilsetningen varer 10 minutter og reaksjonsblandingen oppvarmes deretter under tilbakelbp i 8 timer.
Det faste produkt filtreres og omkrystalliseres i 230 deler etylacetat. Det erholdes 15 deler 1-(m-trifluormetylfenyl)-2-
T(Ø-benzoyloksy-etyl)-amino] -propanhydroklorid, som smelter ved 161°C. iii
10 deler av dette hydroklorid oppslemmes i 100 deler vann. Det j
tilsettes 80 deler eter og deretter 10 deler av en konsentrert opplosning av ammoniumhydroksyd. Stter en kort omroring under ;
hvilken saltet forsvinner, dekanteres og torkes eteropplbsnlngeri.
Etter fjerning av eteren under vakuum, erholdes 9 deler l-(m-trifluormetylfenyl)-2- ftø-benzoyloksy-etyl)-amino]-propan i
form av en fargelos olje.
i
5,5 deler av denne base opplbses i 38 deler absolutt etanol og den således erholdte opplosning tilsettes til 2,2 deler maur-syre i 90 déler absolutt etanol. Det dannede bunnfall opplbses<;>
ved oppvarming. Etter avkjbling og tbrking erholdes 5 deler surt formiat av 1-(m-trif luormetylf enyl)-2-f ((3-benzoyloksy-etyl)-amino]-propan som smelter ved 161-162°C j EKSEMPEL 7-25
Ved hjelp av analoge metoder til den som er beskrevet i eksem- j pel 6, ble fblgende derivater fremstilt: j 1 1
7. 1-(m-trif luormetylf enyl)-2- [(Ø-kloracetyloksy-etyl)- i
amino]-propanhydroklorid, smp. 128-130°C (isopropanol-petroletei) fra 1-(m-trifluormetylfenyl)-2- [(Ø-hydroksy-etyl-amino]-propan og kloreddiksyreklorid. ! 8. Trans-1-(m-trifluormetylfenyl-2-[(Ø-cinnamoyloksyetyl)- j amino]-propanhydroklorid, smp. 159-160°C (etylacetat), fra j l-(m-trifluormetylfenyl)-2-[(0-hydroksy-etyl)-amino]-propan og i transcinnamoylklorid. i
I
9. l-(m-trifluormetylfenyl)-2-[(0-p-klorfenoksyacetyl-oksy-etyl)-amino]-propanhydroklorid, smp. 12lt-125°C (xylen), fra j" 1-(m-trifluormetylfenyl)-2-[(Ø-hydroksy-etyl)-amino]-propan og p-klorfenoksyeddiksyreklorid. 10. 1- (m-trif luormc tyl fenyl) -2- [(|^-f enyl-propionyloksy-e tyl) - amino]-propanhydroklorid, smp. 93~9^°C (ben/.on/cykloheksan) , fra 1- (m-trif luormetylf enyl) -2- [((^-hydroksy-etyl) -amino] -propan og fenylpropionsyreklorid. 11. l-(m-trifluormetylfenyl)-2- [(l^-B' -h ' -dimetylakryloyloksy-etyl)-aminoJ-propanhydroklorid, smp. 153-15't<->C ( isopropanol), fra 1-(m-trifluormetylfenyl)-2-[(^-hydroksy-etyl)-amino] -propan og |3, p-dLmetylakrylsyreklorid. 12. 1- (m-t ri f luormetylf enyl) -2- [(|'-jjfri- tri VI uornicty^-oc-metyl-cinnamoyloksjj-etyl)-amino]-propanhydroklorid, smp. 105-108°C (xylen/cykloheksan) , fra 1-(m-trif luormetylf enyl)-2- [([i-hydroksy-etyl)-aminoJ-propan og m-trifluormetyl-a-metylkanelsyreklorid. 13. 1- (m-trif luormetylf enyl) -2 - L (|<-f enylcyklopentankarboksyl-etyl)-amino]-propanhydroklorid, smp. l'+2°C (etylacetat), fra 1- (m-trif luormetylf enyl) -2- [([•(-hydroksy-etyl) -amino] - propan og fenylcyklopentan-karboksylsyreklorid.
lh. 1- (m-trif luormetylf enyl) -2 - f(|<-o-klor benzoyloksyetyl) - amino]-propanhydroklorid, smp. lV/°C (etylacetat, fra l-(m-trif luormetylf enyl) -2- [(fi-hydroksy-otyl).-amino] -propan og o-klorbenzoylklorid. 15. 1-(m-trifluormetylfenyl)-2-C(p-m-trifluormetylbenzoyl-oksy-etyl) -amino] -propanhydroklorid, smp. 13'/°C (etylacetat),
fra 1- (m-trif luormetylf enyl) -2- [([^-hydroksy-etyl) -amino] -propan og m-trifluormetylbenzoylklorid. 16,. 1- (m-trif luormety] f enyl) -2 - [ ((<-f enylace tyloksy-etyl) - amino]-propanhydroklorid, srnp. 102-10<1>i°C (xyleri), fra l-(m-trifluormetylfenyl)-2-[(p-hydroksy-etyl)-amino]-propan og fenyl-eddiksyreklorid. 17. 1- (m-trif luormetylf enyl) -2-r (f^-p-klorbenzoyloksye tyl) - amino]-propanhydroklorid, smp. 169°C (aceton), fra 1-(m-trifluor- metylf enyl )-2- [(!5-hydroksy-etyl)-amino] -propan og p-klorbenzoylklorid. 18. 1-(m-trifluormetylfenyl)-2-[(|3-p-fluorbenzoyloksyetyl)-amino]-propanhydroklorid, smp. 160-162°C (xylen) fra l-(m-tri-
fluormetylfenyl)-2-[(^-hydroksy-etyl)-amino]-propan og p-fluor-berizoyl klorid. 19. 1 -(m-trifluormetylfenyl)-2-[(^-p-metylbenzoyloksy-etyl)-amino]-propanhydroklorid, smp. l86-l8'/°C (etanol), fra l-(m-trif luormetylf enyl)-2-[ (|3-hydroksy-etyl )-aminoj-propan og p-metylbenzoylklorid. 20. 1- (m-trif luormetylf enyl) -2-[ (|<-a' -f enylbutyryloksy-etyl)-amino]-propanhydroklorid, smp. 109-110°C (etylacetat), fra 1- (m-trif luormetylf enyl) -2-[ (|'3-hydroksy-etyl) -amino] -propan og a-fenylbutyrsyreklorid. 21. l-(m-trifluormetylfenyl-2-[ ((3-3' , h' -metylendioksy-benzoyloksy-etyl)-amino]-propanhydroklorid, smp. 150-151°C (etylacetat), fra 1- (m-t ri f luormetylf enyl) -2 - [ (f3-hydroksy-etyl) - amino]-propan og 3,^-'metylendioksy-benzoylklorid. 22. (m-trifluormetylfenyl)-l-[(p-3',V-dimetyl-benzoyloksyetyl)-amino3-2-propanhydroklorid, smp. 172°C (etanol), fra (m-trif luoretylf enyl) -1- L(|3-hydroksy-etyl) -aminoj -2-propan og 3,^-dimetylbenzoylklorid. 23. (m-trif luormetylf enyl) -l-£ ((3-p-isobutylf enyl-ac etyl oksy-etyl)-aminoj-2-propanhydroklorid, smp. 123°C (etylacetat), fra (m-trif luormetylf enyl) -1-f ((3-hydroksy-etyl) -aminoj -2-propan og p-isobutyl-fenyl-eddiksyreklorid.
2h. 1- (m-trif luormetylf enyl) -2- C([3-p-nitro-benzoyloksy-etyl) ~ amino]-propanhydroklorid, smp. l80-l82°C (etanol), fra l-(m-trif luormetylf enyl) -2-[ (|3-hydroksy-etyl) -aminoj-propan og p-nitrobenzoylklorid. 25. 1-(m>trifluormetylfenyl)-2-[(p-p-amino-benzoyloksy-étyl)-aminoj-propanhydroklorid, smp. 166-168°C (isopropanol), frem- | stilles ved hydrogenering av hydrokloridet av 1-(m-trifluor-
i metylfenyl)-2-r(Ø-p-nitrobenzoyloksy-etyl)-aminoj-propan under et trykk av 6 kg/cm<2>i nærvær av en platinakatalysator, i sus-pensjon i absolutt alkohol.
i FARMAKOLOGISKE EGENSKAPER FOR FREMSTILTE DERIVATER OG ET REFE-RANSEPRODUKT
tabell forts.
N.B. De terapeutiske indekser merket #■ er sammenlignet med den terapeutiske indeks (2) for dl-amfetamin.
(Giftighet P.O.).
De andre indekser er i motsetning sammenlignet med den terapeutiske indeks (1) for dl-amfetamin.
(Giftighet IP).
Claims (1)
- Fremgangsmåte for fremstilling av nye tri fiuormetylderivater av l-fenyl-2-aminopropan for anvendelse som anorexia og med den generelle formel 1:hvor R' betegner et hydrogenatom oller en COK" -gruppe, i hvilken R" betegner et alkylradikal med inntil 6 karbonatomer som kari være substituert med et halogenatom, et karboksyl-, fenyl-, (Lavere alkyl)fenyl- eller halogenfenoksyradikal, et cykloalkyj radikal med }-'/ karbona torner rom kan være substituert med et fenylradikal, et alkenylradikal med 2-6 karbonatomer som kan være substituert med et fenylradikal eller et t ril' l.uo r me ty 11" enylradikal, et fenylradikal som kari være substituert med et halogenatom, et hydroksyl-, metylendioksy-, ni tro-, amino-, t ri !' 1 uormety 1- eller fenylradikal eller med et eller to lavere a.l ky 1 radikaler med opp til<!>+ karbonatomer, i form av racemiske derivater oller optiske isomerer eller i form av addisjonssalter med minera 1 syre r eller organiske syrer,karakterisert vedat man omsotter et trifluor-rnetylfenyl-isopropylamin med don generelle formel II: med etylenoksyd med formelen IV:og at de på denne måte oppnådde forbindelser eventuelt forestres med et funksjonelt derivat av syren R"C00H hvor R" har foran angitte betydning og, hvis onsket, reduseres en nitrogruppe til en aminogruppe under trykk og ved hjelp av en katalysator og, hvis onsket, spaltes de racemiske blandinger med d (-) dibenzoyl-vinsyre for å oppnå venstredreiende isomerer og deretter med d-kamfersyre for å oppnå de tilsvarende hdyredreiende isomerer.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB06660/66A GB1175516A (en) | 1966-04-15 | 1966-04-15 | New Phenyl-Aminopropane Derivatives and Preparations Containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO119801B true NO119801B (no) | 1970-07-06 |
Family
ID=10081320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO167741A NO119801B (no) | 1966-04-15 | 1967-04-14 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US3607909A (no) |
| AT (1) | AT273918B (no) |
| BE (1) | BE696851A (no) |
| CH (1) | CH490330A (no) |
| DK (1) | DK123351B (no) |
| ES (1) | ES339391A1 (no) |
| FI (1) | FI46373C (no) |
| FR (2) | FR1517587A (no) |
| GB (1) | GB1175516A (no) |
| GR (1) | GR32755B (no) |
| NL (1) | NL6705198A (no) |
| NO (1) | NO119801B (no) |
| OA (1) | OA02581A (no) |
| SE (1) | SE327417B (no) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3700680A (en) * | 1967-10-13 | 1972-10-24 | Dainippon Pharmaceutical Co | Aminoalkanol esters and their pharmaceutically acceptable acid-addition salts |
| US4237165A (en) * | 1976-06-04 | 1980-12-02 | Science Union Et Cie | Treatment of carbohydrate metabolism disorders |
| IT1089009B (it) * | 1977-10-28 | 1985-06-10 | Btb Ind Chimica | Processo per la preparazione dell'1-(3-trifluorometilfenil)-2-(2-benzoilossietilammino)-propano |
| FR2502952A1 (fr) * | 1981-04-07 | 1982-10-08 | Science Union & Cie | Nouveau medicament a base de chlorhydrate de benfluorex pour le traitement du diabete |
| FR2684101B1 (fr) * | 1991-11-22 | 1993-12-31 | Adir Cie | Nouveaux derives de benzoate d'ethanolamine, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| DK0863981T3 (da) * | 1996-08-01 | 2010-02-01 | Dale Wallis | Detektering, forebyggelse og behandling af papillomatous digital dermatitis |
| US6083497A (en) * | 1997-11-05 | 2000-07-04 | Geltex Pharmaceuticals, Inc. | Method for treating hypercholesterolemia with unsubstituted polydiallylamine polymers |
| ITMI20012597A1 (it) * | 2001-12-11 | 2003-06-11 | Synteco Spa | Sintesi dell'1-(3-trifluorometilfenil)-2-(-2-benzoilossietilammino)-propano |
| CN100400503C (zh) * | 2006-09-21 | 2008-07-09 | 上海大学 | 5，5，5-三氟-4-(4-甲氧基苯基氨基)戊酸甲酯及其合成方法 |
| US8100429B2 (en) | 2008-03-31 | 2012-01-24 | Artsana Usa, Inc. | Three dimensional folding stroller with infant carrier attachment and one hand actuated seat recline |
| CN101880238B (zh) * | 2010-07-06 | 2014-05-21 | 沈阳药科大学 | 苯甲酸-2-({1-甲基-2-[3-(三氟甲基)-苯基]乙基}氨基)乙酯盐酸盐的制备方法 |
| PE20211065A1 (es) | 2018-07-27 | 2021-06-09 | Xenon Pharmaceuticals Inc | Metodo para tratar la epilepsia |
-
1966
- 1966-04-15 GB GB06660/66A patent/GB1175516A/en not_active Expired
-
1967
- 1967-03-22 SE SE04095/67A patent/SE327417B/xx unknown
- 1967-03-23 GR GR670132755A patent/GR32755B/el unknown
- 1967-03-28 OA OA52836A patent/OA02581A/xx unknown
- 1967-03-31 US US627323A patent/US3607909A/en not_active Expired - Lifetime
- 1967-04-05 FR FR101584A patent/FR1517587A/fr not_active Expired
- 1967-04-10 FI FI671050A patent/FI46373C/fi active
- 1967-04-10 BE BE696851D patent/BE696851A/xx not_active IP Right Cessation
- 1967-04-10 AT AT337367A patent/AT273918B/de active
- 1967-04-13 NL NL6705198A patent/NL6705198A/xx unknown
- 1967-04-14 CH CH530667A patent/CH490330A/fr not_active IP Right Cessation
- 1967-04-14 DK DK205767AA patent/DK123351B/da not_active IP Right Cessation
- 1967-04-14 NO NO167741A patent/NO119801B/no unknown
- 1967-04-15 ES ES339391A patent/ES339391A1/es not_active Expired
-
1968
- 1968-12-23 FR FR112833A patent/FR6564M/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES339391A1 (es) | 1968-10-01 |
| BE696851A (no) | 1967-10-10 |
| GR32755B (el) | 1967-08-29 |
| DK123351B (da) | 1972-06-12 |
| DE1593991B2 (de) | 1973-02-01 |
| FI46373C (fi) | 1973-03-12 |
| CH490330A (fr) | 1970-05-15 |
| DE1593991A1 (de) | 1972-03-16 |
| FI46373B (no) | 1972-11-30 |
| SE327417B (no) | 1970-08-24 |
| FR6564M (no) | 1968-12-23 |
| NL6705198A (no) | 1967-10-16 |
| US3607909A (en) | 1971-09-21 |
| OA02581A (fr) | 1970-05-05 |
| GB1175516A (en) | 1969-12-23 |
| FR1517587A (fr) | 1968-03-15 |
| AT273918B (de) | 1969-08-25 |
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