DE2245141A1 - Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel - Google Patents
Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittelInfo
- Publication number
- DE2245141A1 DE2245141A1 DE2245141A DE2245141A DE2245141A1 DE 2245141 A1 DE2245141 A1 DE 2245141A1 DE 2245141 A DE2245141 A DE 2245141A DE 2245141 A DE2245141 A DE 2245141A DE 2245141 A1 DE2245141 A1 DE 2245141A1
- Authority
- DE
- Germany
- Prior art keywords
- compounds
- formula
- acid
- general formula
- addition salts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 25
- 150000003839 salts Chemical class 0.000 title claims description 17
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 230000008569 process Effects 0.000 title claims description 7
- 229940126601 medicinal product Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 64
- 239000002253 acid Substances 0.000 claims description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- -1 sulfonyloxy group Chemical group 0.000 claims description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 229950004392 norcodeine Drugs 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 239000000829 suppository Substances 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 229950006134 normorphine Drugs 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- 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 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 208000026251 Opioid-Related disease Diseases 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 201000005040 opiate dependence Diseases 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 239000003791 organic solvent mixture Substances 0.000 claims 2
- 239000000839 emulsion Substances 0.000 claims 1
- 239000002360 explosive Substances 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000007795 chemical reaction product Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 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 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 238000009835 boiling Methods 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
- 238000005661 deetherification reaction Methods 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000011877 solvent mixture Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-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
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 2
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- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
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- 230000015556 catabolic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
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- 229960004126 codeine Drugs 0.000 description 2
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- 229940099112 cornstarch Drugs 0.000 description 2
- 238000007257 deesterification reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
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- 239000011707 mineral Substances 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
- HKOIXWVRNLGFOR-KOFBORESSA-N norcodeine Chemical compound O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 HKOIXWVRNLGFOR-KOFBORESSA-N 0.000 description 2
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- 239000012074 organic phase Substances 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
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
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- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
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- 239000007858 starting material Substances 0.000 description 2
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- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
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- 244000215068 Acacia senegal Species 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 238000005985 Hofmann elimination reaction Methods 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical class C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 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
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 150000001639 boron compounds Chemical class 0.000 description 1
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 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
- 125000005521 carbonamide group Chemical group 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
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Natural products C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 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
- 230000001035 methylating effect Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 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
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 150000003565 thiocarboxylic acid derivatives Chemical class 0.000 description 1
- 238000007280 thionation reaction Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Emergency Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Networks Using Active Elements (AREA)
Priority Applications (76)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2245141A DE2245141A1 (de) | 1972-09-14 | 1972-09-14 | Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
| AT761673A AT326281B (de) | 1972-09-14 | 1973-09-03 | Verfahren zur herstellung neuer n- (heteroarylmethyl)-desoxy-normorphine und -norcodeine und deren säureadditionssalze |
| ES418563A ES418563A1 (es) | 1972-09-14 | 1973-09-07 | Procedimiento para la preparacion de n-(heteroarilmetil)- delta7 - desoxi-normorfinas y -norcodeinas. |
| US396171A US3928359A (en) | 1972-09-14 | 1973-09-11 | N-(furyl-or thienyl-methyl)-Desoxy-normorphines and -norcodeines and salt thereof |
| CH207277A CH605958A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH1298673A CH590287A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH198177A CH589089A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH198077A CH589088A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH207077A CH591490A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH207177A CH589090A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| CH207377A CH591491A5 (en, 2012) | 1972-09-14 | 1973-09-11 | |
| DD173479A DD109384A5 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| BG025616A BG21227A3 (bg) | 1972-09-14 | 1973-09-12 | Метод за получаване на n/ хетепоарилметил/ д7- дезокси- норморфини и норкодеини |
| IE1630/73A IE38320B1 (en) | 1972-09-14 | 1973-09-12 | N-(heteroarylmethyl)-desoxy-normorphines and norcodeines |
| BG025613A BG21224A3 (bg) | 1972-09-14 | 1973-09-12 | Метод за получаване на n/ хетероарил метил- / -д7 дезокси норморфини м норкодеини |
| BG025614A BG21225A3 (bg) | 1972-09-14 | 1973-09-12 | Метод за получаване на n / хетероарил метил/-д7- дезокси- норморфини и наркодеини |
| HUBO1463A HU166367B (en, 2012) | 1972-09-14 | 1973-09-12 | |
| SU1962620A SU498911A3 (ru) | 1972-09-14 | 1973-09-12 | Способ получени производных -(гетероарилметил) - -дезоксинорморфинов или -дезоксиноркодеинов |
| BG25617A BG21228A3 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS287*[A CS168679B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| BG025618A BG21229A3 (bg) | 1972-09-14 | 1973-09-12 | Метод за получаване на n/ хетероарилметил/ д7 дезокси- норморфини- норкодеини |
| CS283*[A CS168675B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| BG24524A BG21412A3 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS282*[A CS168674B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS285*[A CS168677B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS286*[A CS168678B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| BG025619A BG21230A3 (bg) | 1972-09-14 | 1973-09-12 | Метод за получаване на n/ хетероарилметил/ д7- дезокси - норморфини и- норкодеини |
| CS6322A CS168673B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS288*[A CS168680B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| CS284*[A CS168676B2 (en, 2012) | 1972-09-14 | 1973-09-12 | |
| PL1973174971A PL91829B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| IL43216A IL43216A (en) | 1972-09-14 | 1973-09-13 | History of N- [furil-)) or thianyl (-methyl] of deoxy-normorphine and nurcodain preparation and pharmaceutical preparations containing them |
| PL1973174970A PL91836B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| PL1973165187A PL87721B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| RO7382817A RO70193A (ro) | 1972-09-14 | 1973-09-13 | Procedeu pentru prepararea n-(heteroaril-metil)-delta 7-dezoxinormorfine si-norcodiene |
| RO7300076068A RO63003A (fr) | 1972-09-14 | 1973-09-13 | Procede pour la preparation des n-(heteroarylmethyl)-deltaen hauf-desoxynomorphines et des norcodeines |
| BE135636A BE804836A (fr) | 1972-09-14 | 1973-09-13 | Nouvelles n-(heteroarylmethyl)-desoxy-normorphines et -norcodeines, leurs sels d'addition avec des acides, leurs procedes de preparation et leur application en tant que medicaments |
| JP48103716A JPS4966700A (en, 2012) | 1972-09-14 | 1973-09-13 | |
| GB4314673A GB1449222A (en) | 1972-09-14 | 1973-09-13 | N-hereroarylmethyl-desoxy-normorphines and-norcodeines |
| AU60301/73A AU479827B2 (en) | 1972-09-14 | 1973-09-13 | N-(heteroarylmethyl)-desoxy-normorphines and norcodeines |
| FI2853/73A FI55512C (fi) | 1972-09-14 | 1973-09-13 | Foerfarande foer framstaellning av pao centralnervsystemet verkande n-(heteroarylmetyl)-7-desoxi-normorfiner och -norkodeiner och motsvarande dihydrofoereningar och deras syraadditionssalter |
| YU02439/73A YU243973A (en) | 1972-09-14 | 1973-09-13 | Process for preparing new n-(hetero-arylmethyl)-deoxy normorphines and norcodeines and corresponding dihydro compounds, respectively |
| PL1973174968A PL90720B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| PL1973174972A PL91807B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| PL1973174969A PL91837B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| PL1973174973A PL91808B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| NL7312621A NL7312621A (en, 2012) | 1972-09-14 | 1973-09-13 | |
| NO3588/73A NO139482C (no) | 1972-09-14 | 1973-09-13 | Analogifremgangsmaate for fremstilling av terapeutisk aktive normorfin- og norkodeinderivater |
| ZA00737289A ZA737289B (en) | 1972-09-14 | 1973-09-13 | Improvements relating to n-heteroarylmethyl)-desoxynormorphines and -norcodeines |
| PL1973174974A PL91809B1 (en, 2012) | 1972-09-14 | 1973-09-13 | |
| SE7312583A SE413510B (sv) | 1972-09-14 | 1973-09-14 | Analogiforfarande for framstellning av n-(furyl- och tienylmetyl)-desoxi-normorfiner och norkodeiner |
| FR7333092A FR2199982B1 (en, 2012) | 1972-09-14 | 1973-09-14 | |
| BG025615A BG21226A3 (bg) | 1972-09-14 | 1974-01-28 | Метод за получаване на n/хетероарилметил/ д7 -де- зокси- нормофини и ниркодеини |
| ES430197A ES430197A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil) - delta7-desoxi-normorfinas y -norcodeina. |
| ES430200A ES430200A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| ES430198A ES430198A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| ES430202A ES430202A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| ES430199A ES430199A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| ES430203A ES430203A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| ES430201A ES430201A1 (es) | 1972-09-14 | 1974-09-19 | Procedimiento para la preparacion de n-(heteroarilmetil - delta7-desoxi-normorfinas y -norcodeinas. |
| SU2063985A SU503523A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени -(гетероарилметил)- -дезокси-нормофинов или -норкодеинов |
| SU2063982A SU528878A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени производных (гетероарилметил)-дезоксинорморфина или- дезоксиноркодеина, или их солей |
| SU2063984A SU520049A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени (гетероарилметил)- дезокси-норморфинов или их дигидросоединений или их солей |
| SU2063986A SU505366A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени -/гетероарилметилдезокси-норморфинов или-норкодеинов |
| SU2063983A SU509239A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени -(гетероарил-метил)- 7-дезокси-норморфиновили -норкодеинов |
| SU2063380A SU503524A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени -(гетероарилметил) -дезокси-норморфинов или -норкодеинов |
| SU2063987A SU506299A3 (ru) | 1972-09-14 | 1974-09-30 | Способ получени -(гетероарилметил)дезоксинорморфинов или -норкодеинов |
| AT932774A AT333441B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-desoxy-normorphine und deren saureadditionssalze |
| AT932974A AT333443B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-desoxy-normorphine und -norcodeine und deren saureadditionssalze |
| AT932574A AT333440B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-dihydro-desoxy-normorphine und -norcodeine und deren saureadditionssalze |
| AT933074A AT333444B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-desoxy-normorphine und -norcodeine und deren saureadditionssalze |
| AT932874A AT333442B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-desoxy-normorphine und -norcodeine und deren saureadditionssalze |
| AT933174A AT333445B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n-(heteroarylmethyl)-desoxy-normorphine und -norcodeine und deren saureadditionssalze |
| AT932674A AT334551B (de) | 1972-09-14 | 1974-11-21 | Verfahren zur herstellung neuer n- (heteroarylmethyl) -desoxynorcodeine und deren saureadditionssalze |
| US05/620,847 US3975368A (en) | 1972-09-14 | 1975-10-08 | Pharmaceutical compositions containing an N-(furyl- or thienyl-methyl)-desoxy-normorphine or norcodeine and method of use |
| YU02548/79A YU254879A (en) | 1972-09-14 | 1979-10-19 | Process for preparing new n-(hetero-arylmethyl)-deoxyy-normorpholines and norcodeines and corresponding dihydro compounds, respectively |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2245141A DE2245141A1 (de) | 1972-09-14 | 1972-09-14 | Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2245141A1 true DE2245141A1 (de) | 1974-03-21 |
Family
ID=5856355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2245141A Pending DE2245141A1 (de) | 1972-09-14 | 1972-09-14 | Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US3928359A (en, 2012) |
| JP (1) | JPS4966700A (en, 2012) |
| AT (1) | AT326281B (en, 2012) |
| BE (1) | BE804836A (en, 2012) |
| BG (8) | BG21229A3 (en, 2012) |
| CH (7) | CH589089A5 (en, 2012) |
| CS (8) | CS168673B2 (en, 2012) |
| DD (1) | DD109384A5 (en, 2012) |
| DE (1) | DE2245141A1 (en, 2012) |
| ES (8) | ES418563A1 (en, 2012) |
| FI (1) | FI55512C (en, 2012) |
| FR (1) | FR2199982B1 (en, 2012) |
| GB (1) | GB1449222A (en, 2012) |
| HU (1) | HU166367B (en, 2012) |
| IE (1) | IE38320B1 (en, 2012) |
| IL (1) | IL43216A (en, 2012) |
| NL (1) | NL7312621A (en, 2012) |
| NO (1) | NO139482C (en, 2012) |
| PL (8) | PL91809B1 (en, 2012) |
| RO (2) | RO70193A (en, 2012) |
| SE (1) | SE413510B (en, 2012) |
| SU (8) | SU498911A3 (en, 2012) |
| YU (2) | YU243973A (en, 2012) |
| ZA (1) | ZA737289B (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4236008A (en) * | 1978-09-19 | 1980-11-25 | E. I. Du Pont De Nemours And Company | Fluorination of precursors for fluorine analogs of hydrocodone and oxycodone |
| US4241065A (en) * | 1979-07-02 | 1980-12-23 | E. I. Du Pont De Nemours And Company | Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both |
| CA2319627A1 (en) * | 1998-01-29 | 1999-08-05 | Polychip Pharmaceuticals Pty. Ltd. | Therapeutic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2107989A1 (de) * | 1971-02-19 | 1972-09-07 | Boehringer Sohn Ingelheim | N-(Furyl-methy])-morphinane, deren Säureadditionssalze sowie Verfahren zu deren Herstellung |
-
1972
- 1972-09-14 DE DE2245141A patent/DE2245141A1/de active Pending
-
1973
- 1973-09-03 AT AT761673A patent/AT326281B/de not_active IP Right Cessation
- 1973-09-07 ES ES418563A patent/ES418563A1/es not_active Expired
- 1973-09-11 CH CH198177A patent/CH589089A5/xx not_active IP Right Cessation
- 1973-09-11 US US396171A patent/US3928359A/en not_active Expired - Lifetime
- 1973-09-11 CH CH207077A patent/CH591490A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207377A patent/CH591491A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH198077A patent/CH589088A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207277A patent/CH605958A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207177A patent/CH589090A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH1298673A patent/CH590287A5/xx not_active IP Right Cessation
- 1973-09-12 BG BG025618A patent/BG21229A3/xx unknown
- 1973-09-12 BG BG025619A patent/BG21230A3/xx unknown
- 1973-09-12 CS CS6322A patent/CS168673B2/cs unknown
- 1973-09-12 DD DD173479A patent/DD109384A5/xx unknown
- 1973-09-12 CS CS283*[A patent/CS168675B2/cs unknown
- 1973-09-12 SU SU1962620A patent/SU498911A3/ru active
- 1973-09-12 CS CS282*[A patent/CS168674B2/cs unknown
- 1973-09-12 IE IE1630/73A patent/IE38320B1/xx unknown
- 1973-09-12 CS CS285*[A patent/CS168677B2/cs unknown
- 1973-09-12 CS CS284*[A patent/CS168676B2/cs unknown
- 1973-09-12 BG BG025616A patent/BG21227A3/xx unknown
- 1973-09-12 BG BG24524A patent/BG21412A3/xx unknown
- 1973-09-12 BG BG025614A patent/BG21225A3/xx unknown
- 1973-09-12 CS CS287*[A patent/CS168679B2/cs unknown
- 1973-09-12 CS CS288*[A patent/CS168680B2/cs unknown
- 1973-09-12 BG BG25617A patent/BG21228A3/xx unknown
- 1973-09-12 BG BG025613A patent/BG21224A3/xx unknown
- 1973-09-12 CS CS286*[A patent/CS168678B2/cs unknown
- 1973-09-12 HU HUBO1463A patent/HU166367B/hu unknown
- 1973-09-13 RO RO7382817A patent/RO70193A/ro unknown
- 1973-09-13 PL PL1973174974A patent/PL91809B1/pl unknown
- 1973-09-13 PL PL1973174969A patent/PL91837B1/pl unknown
- 1973-09-13 PL PL1973174970A patent/PL91836B1/pl unknown
- 1973-09-13 NO NO3588/73A patent/NO139482C/no unknown
- 1973-09-13 PL PL1973174971A patent/PL91829B1/pl unknown
- 1973-09-13 NL NL7312621A patent/NL7312621A/xx not_active Application Discontinuation
- 1973-09-13 JP JP48103716A patent/JPS4966700A/ja active Pending
- 1973-09-13 FI FI2853/73A patent/FI55512C/fi active
- 1973-09-13 IL IL43216A patent/IL43216A/en unknown
- 1973-09-13 PL PL1973174972A patent/PL91807B1/pl unknown
- 1973-09-13 BE BE135636A patent/BE804836A/xx unknown
- 1973-09-13 PL PL1973165187A patent/PL87721B1/pl unknown
- 1973-09-13 ZA ZA00737289A patent/ZA737289B/xx unknown
- 1973-09-13 PL PL1973174973A patent/PL91808B1/pl unknown
- 1973-09-13 YU YU02439/73A patent/YU243973A/xx unknown
- 1973-09-13 PL PL1973174968A patent/PL90720B1/pl unknown
- 1973-09-13 GB GB4314673A patent/GB1449222A/en not_active Expired
- 1973-09-13 RO RO7300076068A patent/RO63003A/ro unknown
- 1973-09-14 SE SE7312583A patent/SE413510B/xx unknown
- 1973-09-14 FR FR7333092A patent/FR2199982B1/fr not_active Expired
-
1974
- 1974-01-28 BG BG025615A patent/BG21226A3/bg unknown
- 1974-09-19 ES ES430199A patent/ES430199A1/es not_active Expired
- 1974-09-19 ES ES430201A patent/ES430201A1/es not_active Expired
- 1974-09-19 ES ES430200A patent/ES430200A1/es not_active Expired
- 1974-09-19 ES ES430203A patent/ES430203A1/es not_active Expired
- 1974-09-19 ES ES430202A patent/ES430202A1/es not_active Expired
- 1974-09-19 ES ES430198A patent/ES430198A1/es not_active Expired
- 1974-09-19 ES ES430197A patent/ES430197A1/es not_active Expired
- 1974-09-30 SU SU2063986A patent/SU505366A3/ru active
- 1974-09-30 SU SU2063380A patent/SU503524A3/ru active
- 1974-09-30 SU SU2063983A patent/SU509239A3/ru active
- 1974-09-30 SU SU2063987A patent/SU506299A3/ru active
- 1974-09-30 SU SU2063985A patent/SU503523A3/ru active
- 1974-09-30 SU SU2063984A patent/SU520049A3/ru active
- 1974-09-30 SU SU2063982A patent/SU528878A3/ru active
-
1979
- 1979-10-19 YU YU02548/79A patent/YU254879A/xx unknown
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