NO134055B - - Google Patents
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- Publication number
- NO134055B NO134055B NO491/72A NO49172A NO134055B NO 134055 B NO134055 B NO 134055B NO 491/72 A NO491/72 A NO 491/72A NO 49172 A NO49172 A NO 49172A NO 134055 B NO134055 B NO 134055B
- Authority
- NO
- Norway
- Prior art keywords
- formula
- methyl
- compounds
- hydrogen atom
- morphinan
- Prior art date
Links
- 238000000034 method Methods 0.000 claims abstract description 75
- DLKZLCYLOHSIOQ-HBMCJLEFSA-N (1R,9R,10R)-17-(furan-2-ylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2,4,6-triene Chemical class O1C(=CC=C1)CN1[C@H]2[C@@H]3CCCC[C@@]3(C=3C=CC=CC=3C2)CC1 DLKZLCYLOHSIOQ-HBMCJLEFSA-N 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 82
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 18
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000002240 furans Chemical class 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- IYNWSQDZXMGGGI-NUEKZKHPSA-N 3-hydroxymorphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(O)C=C4[C@]21CCN3 IYNWSQDZXMGGGI-NUEKZKHPSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- -1 N-furoylmorphinane Chemical compound 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- SLGUAJQWZVMGFJ-CEWLAPEOSA-N (1R,9R,10R)-17-(furan-2-ylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol Chemical compound C(C1=CC=CO1)N1[C@H]2[C@@H]3CCCC[C@@]3(C=3C=C(C=CC3C2)O)CC1 SLGUAJQWZVMGFJ-CEWLAPEOSA-N 0.000 description 7
- IYNWSQDZXMGGGI-KBMXLJTQSA-N nordextrorphan Chemical compound C1CCC[C@@H]2[C@@H]3CC4=CC=C(O)C=C4[C@@]21CCN3 IYNWSQDZXMGGGI-KBMXLJTQSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- HLPIHRDZBHXTFJ-UHFFFAOYSA-N 2-ethylfuran Chemical compound CCC1=CC=CO1 HLPIHRDZBHXTFJ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- SLROTKFSBGWEDD-PDTFXZCISA-N (4r,4ar,7s,7ar,12bs)-3-methyl-1,2,4,4a,7,7a,10,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9,9-triol Chemical compound O[C@H]([C@@H]1O2)C=C[C@H]3[C@]4([H])N(C)CC[C@@]31C1=C2C(O)(O)CC=C1C4 SLROTKFSBGWEDD-PDTFXZCISA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- GANBJDIOIDQSGI-UHFFFAOYSA-N 2-(chloromethyl)furan Chemical compound ClCC1=CC=CO1 GANBJDIOIDQSGI-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UNOVUFCKLCCGEU-KSEOMHKRSA-N (1R,9R,10R)-17-[(5-methylfuran-2-yl)methyl]-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol Chemical compound CC1=CC=C(CN2CC[C@]34CCCC[C@H]3[C@H]2CC2=C4C=C(O)C=C2)O1 UNOVUFCKLCCGEU-KSEOMHKRSA-N 0.000 description 3
- XXTMIGSYISUNAZ-UHFFFAOYSA-N 3-(chloromethyl)-2-ethylfuran Chemical compound CCC=1OC=CC=1CCl XXTMIGSYISUNAZ-UHFFFAOYSA-N 0.000 description 3
- WBQMCHYYCSCXID-UHFFFAOYSA-N 3-(chloromethyl)-2-methylfuran Chemical compound CC=1OC=CC=1CCl WBQMCHYYCSCXID-UHFFFAOYSA-N 0.000 description 3
- WECUIJXZKLGURU-UHFFFAOYSA-N 3-(chloromethyl)furan Chemical compound ClCC=1C=COC=1 WECUIJXZKLGURU-UHFFFAOYSA-N 0.000 description 3
- ILNSWVUXAPSPEH-USXIJHARSA-N 3-methoxy-morphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(OC)C=C4[C@]21CCN3 ILNSWVUXAPSPEH-USXIJHARSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-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
- LKTNPXAQSJXTPD-TYMHPWAKSA-N [(1R,9R,10R)-17-(furan-2-ylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] acetate hydrochloride Chemical compound Cl.C(C1=CC=CO1)N1[C@H]2[C@@H]3CCCC[C@@]3(C=3C=C(C=CC3C2)OC(C)=O)CC1 LKTNPXAQSJXTPD-TYMHPWAKSA-N 0.000 description 3
- 239000002026 chloroform extract Substances 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
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SYBIFAOTBKJVTN-KSEOMHKRSA-N (1R,9R,10R)-17-(furan-2-ylmethyl)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene Chemical compound C(C1=CC=CO1)N1[C@H]2[C@@H]3CCCC[C@@]3(C=3C=C(C=CC3C2)OC)CC1 SYBIFAOTBKJVTN-KSEOMHKRSA-N 0.000 description 2
- IHCBNYUHZNMHPG-CZTZKLFOSA-N (1R,9R,10R)-17-[(3-methylfuran-2-yl)methyl]-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol Chemical compound CC1=C(CN2[C@H]3[C@@H]4CCCC[C@@]4(C=4C=C(C=CC4C3)O)CC2)OC=C1 IHCBNYUHZNMHPG-CZTZKLFOSA-N 0.000 description 2
- SULMLDLKFPWNNP-MDNUFGMLSA-N (1R,9R,10R)-17-[(5-ethylfuran-2-yl)methyl]-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol Chemical compound C(C)C1=CC=C(CN2[C@H]3[C@@H]4CCCC[C@@]4(C=4C=C(C=CC4C3)O)CC2)O1 SULMLDLKFPWNNP-MDNUFGMLSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 2
- DFXNZMRXFMWEGQ-UHFFFAOYSA-N 3-methylfuran-2-carbonyl chloride Chemical compound CC=1C=COC=1C(Cl)=O DFXNZMRXFMWEGQ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
- 241000906446 Theraps Species 0.000 description 2
- ZSXOMZNITRYAGE-MDNUFGMLSA-N [(1R,9R,10R)-17-(furan-2-ylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] acetate Chemical compound C(C1=CC=CO1)N1[C@H]2[C@@H]3CCCC[C@@]3(C=3C=C(C=CC3C2)OC(C)=O)CC1 ZSXOMZNITRYAGE-MDNUFGMLSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- NGPGDYLVALNKEG-OLXYHTOASA-N diammonium L-tartrate Chemical class [NH4+].[NH4+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O NGPGDYLVALNKEG-OLXYHTOASA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000001256 steam distillation Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
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- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
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- QJGNDZGCUZOKFV-UHFFFAOYSA-N 3-methyl-2H-furan-3-carbonyl chloride Chemical compound CC1(COC=C1)C(=O)Cl QJGNDZGCUZOKFV-UHFFFAOYSA-N 0.000 description 1
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- DNXMWVZQLPNQQB-UHFFFAOYSA-N 4-methylfuran-2-carbonyl chloride Chemical compound CC1=COC(C(Cl)=O)=C1 DNXMWVZQLPNQQB-UHFFFAOYSA-N 0.000 description 1
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- 239000005711 Benzoic acid Substances 0.000 description 1
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- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 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
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 238000003436 Schotten-Baumann reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 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 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- PWXMEBZOKUPCST-UHFFFAOYSA-N methyl 5-(chloromethyl)furan-2-carboxylate Chemical compound COC(=O)C1=CC=C(CCl)O1 PWXMEBZOKUPCST-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 229940051807 opiod analgesics morphinan derivative Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 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
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000005486 sulfidation Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712107989 DE2107989A1 (de) | 1971-02-19 | 1971-02-19 | N-(Furyl-methy])-morphinane, deren Säureadditionssalze sowie Verfahren zu deren Herstellung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO134055B true NO134055B (sl) | 1976-05-03 |
| NO134055C NO134055C (sl) | 1976-08-11 |
Family
ID=5799263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO491/72A NO134055C (sl) | 1971-02-19 | 1972-02-18 |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US3793329A (sl) |
| AT (3) | AT318600B (sl) |
| AU (1) | AU468490B2 (sl) |
| BE (1) | BE779582A (sl) |
| BG (4) | BG20356A3 (sl) |
| CA (1) | CA969180A (sl) |
| CH (2) | CH567503A5 (sl) |
| CS (4) | CS166807B2 (sl) |
| DD (1) | DD96484A5 (sl) |
| DE (1) | DE2107989A1 (sl) |
| DK (1) | DK136721C (sl) |
| ES (4) | ES399875A1 (sl) |
| FR (1) | FR2125599B1 (sl) |
| GB (1) | GB1379781A (sl) |
| HU (1) | HU162947B (sl) |
| IE (1) | IE36116B1 (sl) |
| IL (1) | IL38788A (sl) |
| NL (1) | NL7202153A (sl) |
| NO (1) | NO134055C (sl) |
| PH (1) | PH10385A (sl) |
| PL (1) | PL77393B1 (sl) |
| RO (4) | RO63019A (sl) |
| SE (1) | SE363826B (sl) |
| SU (3) | SU466658A3 (sl) |
| ZA (1) | ZA721072B (sl) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2229770A1 (de) * | 1972-06-19 | 1974-01-10 | Boehringer Sohn Ingelheim | N-(heteroarylmethyl)-7alpha-acyl6,14-endoaethenotetrahydro-nororipavine und -thebaine, deren hydrierungsprodukte und saeureadditionssalze sowie verfahren zu deren herstellung |
| DE2230154A1 (de) * | 1972-06-21 | 1974-01-17 | Boehringer Sohn Ingelheim | N-(heteroaryl-methyl)-6,14-endoaetheno7alpha-hydroxyalkyl-tetrahydro-nororipavine und -thebaine, deren hydrierungsprodukte und saeureadditionssalze sowie verfahren zu deren herstellung |
| US3923987A (en) * | 1972-08-07 | 1975-12-02 | Boehringer Sohn Ingelheim | Pharmaceutical compositions containing an n-furyl-or thienyl-methyl)- -oxy-7,8 -dihydro-normorphinone or norcodeinone and method of use |
| DE2238839A1 (de) * | 1972-08-07 | 1974-02-14 | Boehringer Sohn Ingelheim | Neue morphinon-derivate, deren saeureadditionssalze, verfahren zu ihrer herstellung sowie ihre verwendung zur herstellung von arzneimitteln |
| US3975368A (en) * | 1972-09-14 | 1976-08-17 | Boehringer Ingelheim Gmbh | Pharmaceutical compositions containing an N-(furyl- or thienyl-methyl)-desoxy-normorphine or norcodeine and method of use |
| DE2245141A1 (de) * | 1972-09-14 | 1974-03-21 | Boehringer Sohn Ingelheim | Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
| US4232026A (en) * | 1978-07-20 | 1980-11-04 | Merck & Co., Inc. | Diazaditwistanes, and pharmaceutical compositions for treating pain in warm blooded animals containing them |
| US7923454B2 (en) * | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| GB0421687D0 (en) † | 2004-09-30 | 2004-11-03 | Johnson Matthey Plc | Preparation of opiate analgesics |
| WO2007137785A2 (en) * | 2006-05-25 | 2007-12-06 | Alpharma (Bermuda) Investments Ltd | Process useful in the preparation of morphinan antagonists |
| GB2471800B (en) * | 2006-05-25 | 2011-03-09 | Alpharma | Preparation of N-alkylated morphinans by reduction of an iminium group |
| KR100780932B1 (ko) * | 2006-05-30 | 2007-11-30 | 엠텍비젼 주식회사 | 컬러 보간 방법 및 장치 |
| US10766864B2 (en) | 2015-05-08 | 2020-09-08 | Nektar Therapeutics | Morphinan derivatives for the treatment of neuropathic pain |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL99456C (sl) * | 1957-12-04 |
-
1971
- 1971-02-19 DE DE19712107989 patent/DE2107989A1/de active Pending
-
1972
- 1972-02-09 US US00224973A patent/US3793329A/en not_active Expired - Lifetime
- 1972-02-10 RO RO7200076826A patent/RO63019A/ro unknown
- 1972-02-14 PH PH13267A patent/PH10385A/en unknown
- 1972-02-16 CH CH755175A patent/CH567503A5/xx not_active IP Right Cessation
- 1972-02-16 RO RO7200076824A patent/RO63012A/ro unknown
- 1972-02-16 CH CH219772A patent/CH567501A5/xx not_active IP Right Cessation
- 1972-02-16 RO RO7200069780A patent/RO62412A/ro unknown
- 1972-02-16 RO RO7200076825A patent/RO63262A/ro unknown
- 1972-02-17 CS CS3426*A patent/CS166807B2/cs unknown
- 1972-02-17 HU HUBO1351A patent/HU162947B/hu unknown
- 1972-02-17 SU SU1939076A patent/SU466658A3/ru active
- 1972-02-17 BG BG021203A patent/BG20356A3/xx unknown
- 1972-02-17 BG BG021205A patent/BG22833A3/xx unknown
- 1972-02-17 BG BG019747A patent/BG20584A3/xx unknown
- 1972-02-17 ES ES72399875A patent/ES399875A1/es not_active Expired
- 1972-02-17 CS CS1036A patent/CS166805B2/cs unknown
- 1972-02-17 CS CS3425*A patent/CS166806B2/cs unknown
- 1972-02-17 SU SU1939073A patent/SU481155A3/ru active
- 1972-02-17 BG BG021204A patent/BG20357A3/xx unknown
- 1972-02-17 CS CS3427*A patent/CS166808B2/cs unknown
- 1972-02-18 AT AT108373A patent/AT318600B/de not_active IP Right Cessation
- 1972-02-18 IL IL38788A patent/IL38788A/xx unknown
- 1972-02-18 DK DK76972A patent/DK136721C/da active
- 1972-02-18 DD DD160981A patent/DD96484A5/xx unknown
- 1972-02-18 NL NL7202153A patent/NL7202153A/xx unknown
- 1972-02-18 CA CA135,013A patent/CA969180A/en not_active Expired
- 1972-02-18 NO NO491/72A patent/NO134055C/no unknown
- 1972-02-18 AT AT108273A patent/AT318599B/de not_active IP Right Cessation
- 1972-02-18 ZA ZA721072A patent/ZA721072B/xx unknown
- 1972-02-18 GB GB765072A patent/GB1379781A/en not_active Expired
- 1972-02-18 IE IE206/72A patent/IE36116B1/xx unknown
- 1972-02-18 SE SE02039/72A patent/SE363826B/xx unknown
- 1972-02-18 FR FR7205575A patent/FR2125599B1/fr not_active Expired
- 1972-02-18 AT AT01364/72A patent/AT312588B/de active
- 1972-02-18 BE BE779582A patent/BE779582A/xx unknown
- 1972-02-18 AU AU39140/72A patent/AU468490B2/en not_active Expired
- 1972-02-18 PL PL1972153546A patent/PL77393B1/pl unknown
-
1973
- 1973-06-25 SU SU1940421A patent/SU488411A3/ru active
- 1973-11-17 ES ES420629A patent/ES420629A1/es not_active Expired
- 1973-11-17 ES ES420630A patent/ES420630A1/es not_active Expired
- 1973-11-17 ES ES420628A patent/ES420628A1/es not_active Expired
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