NO823707L - Fremgangsmaate for fremstilling av terapeutisk aktive morfinanderivater. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive morfinanderivater.Info
- Publication number
- NO823707L NO823707L NO823707A NO823707A NO823707L NO 823707 L NO823707 L NO 823707L NO 823707 A NO823707 A NO 823707A NO 823707 A NO823707 A NO 823707A NO 823707 L NO823707 L NO 823707L
- Authority
- NO
- Norway
- Prior art keywords
- lower alkyl
- alkyl
- aryl
- compound
- heteroaryl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title description 6
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- -1 trifluoromethylcarbonyl Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- QAPLLQSUWNDGSK-QXAKKESOSA-N (-)-3-acetyl-n-methylmorphinan Chemical compound C1CCC[C@H]2[C@]3([H])N(C)CC[C@@]21C1=CC(C(C)=O)=CC=C1C3 QAPLLQSUWNDGSK-QXAKKESOSA-N 0.000 claims description 7
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims description 4
- VSGPHNHYKRDWBH-KSEOMHKRSA-N 3-acpmm Chemical compound C([C@]12CCCC[C@H]1[C@H]1CC3=CC=C(C=C32)C(=O)C)CN1CC1CC1 VSGPHNHYKRDWBH-KSEOMHKRSA-N 0.000 claims description 3
- 229940051807 opiod analgesics morphinan derivative Drugs 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
- QNRDGWCQFQJLSA-ILZDJORESA-N 1-[(1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl]propan-1-one Chemical compound C1CCC[C@H]2[C@]3([H])N(C)CC[C@@]21C1=CC(C(=O)CC)=CC=C1C3 QNRDGWCQFQJLSA-ILZDJORESA-N 0.000 claims description 2
- GXGJIOMUZAGVEH-UHFFFAOYSA-N Chamazulene Chemical group CCC1=CC=C(C)C2=CC=C(C)C2=C1 GXGJIOMUZAGVEH-UHFFFAOYSA-N 0.000 claims description 2
- ILPOFDRRJCJAHC-SKBVVQJISA-N chembl277576 Chemical compound C([C@@]12C3=CC(=CC=C3C[C@@]3([C@@H]1CCCC2)[H])C(C)=O)CN3CCC1=CC=CC=C1 ILPOFDRRJCJAHC-SKBVVQJISA-N 0.000 claims description 2
- NEZTVUIFXBALAE-SXZRXXEVSA-N chembl280512 Chemical compound C([C@H]12)CCC[C@@]11CCN(C)[C@@H]2CC2=CC=C(C(O)C)C=C21 NEZTVUIFXBALAE-SXZRXXEVSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 235000013405 beer Nutrition 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 239000000203 mixture Substances 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000009835 boiling Methods 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229920000881 Modified starch Polymers 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- VCAYJGGOEVQAQS-CGTJXYLNSA-N (-)-1-(morphinan-3-yl)ethanone Chemical compound C1CCC[C@H]2[C@]3([H])NCC[C@@]21C1=CC(C(C)=O)=CC=C1C3 VCAYJGGOEVQAQS-CGTJXYLNSA-N 0.000 description 6
- 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 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 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 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000004368 Modified starch Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229960001270 d- tartaric acid Drugs 0.000 description 4
- 239000012259 ether extract Substances 0.000 description 4
- 235000019426 modified starch Nutrition 0.000 description 4
- 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 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- QRAZKEXVYWLPTK-OTWHNJEPSA-N (-)-2-acetyl-n-methylmorphinan Chemical compound C1CCC[C@H]2[C@]3([H])N(C)CC[C@@]21C1=CC=C(C(C)=O)C=C1C3 QRAZKEXVYWLPTK-OTWHNJEPSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 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
- 239000008120 corn starch Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- JILHELPRIZUEPJ-ILZDJORESA-N (-)-3-acetylmorphinan-17-carboxylic acid (trichloroethyl)ester Chemical compound C1CCC[C@H]2[C@]3([H])N(C(=O)OCC(Cl)(Cl)Cl)CC[C@@]21C1=CC(C(C)=O)=CC=C1C3 JILHELPRIZUEPJ-ILZDJORESA-N 0.000 description 2
- AHOFVRTVWPRWRJ-VNMUXGFYSA-N (1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2,4,6-triene hydrochloride Chemical compound Cl.C1CCC[C@H]2[C@]3([H])N(C)CC[C@@]21C1=CC=CC=C1C3 AHOFVRTVWPRWRJ-VNMUXGFYSA-N 0.000 description 2
- GMUHWBPOUAVNHE-QPTUXGOLSA-N 1-[(1R,9R,10R)-17-[2-(furan-2-yl)ethyl]-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl]ethanone Chemical compound C([C@@]12C3=CC(=CC=C3C[C@@]3([C@@H]1CCCC2)[H])C(C)=O)CN3CCC1=CC=CO1 GMUHWBPOUAVNHE-QPTUXGOLSA-N 0.000 description 2
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 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
- 229910015900 BF3 Inorganic materials 0.000 description 2
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
- 239000007818 Grignard reagent Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- SDFSTVBYPPYEOS-BGWNEDDSSA-N [(1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl]-phenylmethanone Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C)[H])C2=CC=C3C(=O)C1=CC=CC=C1 SDFSTVBYPPYEOS-BGWNEDDSSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound 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 2
- 229960004126 codeine Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 150000002900 organolithium compounds Chemical class 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- YSCVYRUCAPMZFG-UHFFFAOYSA-K trichlorotin Chemical compound Cl[Sn](Cl)Cl YSCVYRUCAPMZFG-UHFFFAOYSA-K 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- BPPBEIPHIFOMLG-MDNUFGMLSA-N (-)-1-[17-(3-methyl-2-butenyl)morphinan-3-yl]ethanone Chemical compound C1CCC[C@H]2[C@]3([H])N(CC=C(C)C)CC[C@@]21C1=CC(C(C)=O)=CC=C1C3 BPPBEIPHIFOMLG-MDNUFGMLSA-N 0.000 description 1
- JYZRMQDRPOMKEY-CEWLAPEOSA-N (-)-3-acetyl-17-morphinanpropanenitrile Chemical compound C1CCC[C@H]2[C@]3([H])N(CCC#N)CC[C@@]21C1=CC(C(C)=O)=CC=C1C3 JYZRMQDRPOMKEY-CEWLAPEOSA-N 0.000 description 1
- AQNXSFRFUICTRP-BGWNEDDSSA-N (-)-3-acetyl-n-[(2-furylmethyl)carbonyl]morphinan Chemical compound C([C@@]12C3=CC(=CC=C3C[C@@]3([C@@H]1CCCC2)[H])C(C)=O)CN3C(=O)CC1=CC=CO1 AQNXSFRFUICTRP-BGWNEDDSSA-N 0.000 description 1
- WWCDIERWUIOBDL-MDNUFGMLSA-N (-)-3-acetyl-n-cyclobutylmethylmorphinan Chemical compound C([C@@]12C3=CC(=CC=C3C[C@@]3([C@@H]1CCCC2)[H])C(C)=O)CN3CC1CCC1 WWCDIERWUIOBDL-MDNUFGMLSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
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- 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
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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Classifications
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- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/28—Morphinans
-
- 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)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/319,482 US4374139A (en) | 1981-11-09 | 1981-11-09 | Levorotatory N-substituted acylmorphinans useful as analgesic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO823707L true NO823707L (no) | 1983-05-10 |
Family
ID=23242421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO823707A NO823707L (no) | 1981-11-09 | 1982-11-08 | Fremgangsmaate for fremstilling av terapeutisk aktive morfinanderivater. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4374139A (xx) |
| EP (1) | EP0079556A3 (xx) |
| JP (1) | JPS5888364A (xx) |
| KR (1) | KR840002357A (xx) |
| AU (1) | AU9027682A (xx) |
| CA (1) | CA1195324A (xx) |
| DK (1) | DK491582A (xx) |
| ES (2) | ES517222A0 (xx) |
| FI (1) | FI823824L (xx) |
| GR (1) | GR78317B (xx) |
| HU (1) | HU187425B (xx) |
| IL (1) | IL67180A0 (xx) |
| MC (1) | MC1490A1 (xx) |
| NO (1) | NO823707L (xx) |
| NZ (1) | NZ202404A (xx) |
| PH (1) | PH18458A (xx) |
| PT (1) | PT75815B (xx) |
| ZA (1) | ZA827905B (xx) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4423221A (en) * | 1982-06-10 | 1983-12-27 | Sisa Pharmaceutical Laboratories, Inc. | 7-Carboethoxy-morphinan-6-one compounds |
| US4454141A (en) * | 1982-09-23 | 1984-06-12 | Sisa Pharmaceutical Laboratories, Inc. | Trans-B/C-7-(1-hydroxypentyl)-3-methoxy-17 methyl-6,7-didehydromorphinans, and methods of relieving pain with them |
| EP0184041A1 (en) * | 1984-11-13 | 1986-06-11 | Miles Inc. | 6-Methylene morphinan purification technique |
| US4929622A (en) * | 1987-09-24 | 1990-05-29 | Hoechst-Roussel Pharmaceuticals, Inc. | 2,6-Methanopyrrolo-3-benzazocines |
| DE4304450A1 (de) * | 1993-02-13 | 1994-08-18 | Boehringer Mannheim Gmbh | System zur Zubereitung von Flüssigkeiten |
| EP1353909B1 (en) | 2000-10-31 | 2005-04-06 | Rensselaer Polytechnic Institute | 8-substituted-2,6-methano-3-benzazocines and 3-substituted morphinanes as opioidreceptor binding agents |
| ATE445838T1 (de) | 2001-07-25 | 2009-10-15 | Raptor Pharmaceutical Inc | Zusammensetzungen und verfahren zur modulation des transports durch die blut-hirn-schranke |
| US20040204862A1 (en) * | 2003-04-11 | 2004-10-14 | Wainer Irving W. | Computer-based model for identification and characterization for non-competitive inhibitors of nicotinic acetylcholine receptors and related ligand-gated ion channel receptors |
| DK1889198T3 (da) | 2005-04-28 | 2015-02-09 | Proteus Digital Health Inc | Farma-informatiksystem |
| WO2008036682A2 (en) | 2006-09-18 | 2008-03-27 | Raptor Pharmaceutical Inc. | Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates |
| ES2728225T3 (es) | 2009-02-20 | 2019-10-23 | 2 Bbb Medicines B V | Sistema de administración de fármacos a base de glutatión |
| US8445002B2 (en) | 2009-05-06 | 2013-05-21 | Laboratory Skin Care, Inc. | Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same |
| NZ600379A (en) | 2009-12-04 | 2014-05-30 | Alkermes Pharma Ireland Ltd | Morphinan derivatives for the treatment of drug overdose |
| JP5964809B2 (ja) | 2010-03-22 | 2016-08-03 | レンセラール ポリテクニック インスティチュート | オピオイド受容体リガンドとしてのカルボキサミド基を含有するモルヒネ誘導体 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
| LT2725908T (lt) | 2011-06-29 | 2017-09-11 | Alkermes, Inc. | Periferinio poveikio opioidų junginiai |
| US9211293B2 (en) | 2011-12-15 | 2015-12-15 | Alkermes Pharma Ireland Limited | Opioid agonist antagonist combinations |
| CA2911231C (en) | 2013-05-24 | 2021-12-07 | Alkermes Pharma Ireland Limited | Morphan and morphinan analogues, and methods of use |
| US9656961B2 (en) | 2013-05-24 | 2017-05-23 | Alkermes Pharma Ireland Limited | Methods for treating depressive symptoms |
| WO2018125716A1 (en) * | 2017-01-02 | 2018-07-05 | Purdue Pharma L.P. | Morphinan derivatives and use thereof |
| EP4243768A1 (en) | 2020-11-12 | 2023-09-20 | Alkermes Pharma Ireland Limited | Immediate release multilayer tablet |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3723437A (en) * | 1970-09-15 | 1973-03-27 | American Home Prod | 4,10-(methaniminomethano phenanthrene derivatives |
| ZA73988B (en) * | 1972-03-10 | 1973-10-31 | Hoffmann La Roche | Morphinan derivatives |
| US3914233A (en) * | 1972-10-20 | 1975-10-21 | Hoffmann La Roche | 4-Hydroxy-N-substituted morphinan derivatives |
-
1981
- 1981-11-09 US US06/319,482 patent/US4374139A/en not_active Expired - Fee Related
- 1981-12-29 GR GR69729A patent/GR78317B/el unknown
-
1982
- 1982-10-28 ZA ZA827905A patent/ZA827905B/xx unknown
- 1982-11-05 DK DK491582A patent/DK491582A/da not_active Application Discontinuation
- 1982-11-05 IL IL67180A patent/IL67180A0/xx unknown
- 1982-11-05 NZ NZ202404A patent/NZ202404A/en unknown
- 1982-11-08 EP EP82110285A patent/EP0079556A3/de not_active Ceased
- 1982-11-08 MC MC821609A patent/MC1490A1/xx unknown
- 1982-11-08 HU HU823578A patent/HU187425B/hu unknown
- 1982-11-08 CA CA000415102A patent/CA1195324A/en not_active Expired
- 1982-11-08 FI FI823824A patent/FI823824L/fi not_active Application Discontinuation
- 1982-11-08 ES ES517222A patent/ES517222A0/es active Granted
- 1982-11-08 PH PH28105A patent/PH18458A/en unknown
- 1982-11-08 NO NO823707A patent/NO823707L/no unknown
- 1982-11-08 PT PT75815A patent/PT75815B/pt unknown
- 1982-11-08 JP JP57194799A patent/JPS5888364A/ja active Pending
- 1982-11-09 KR KR1019820005066A patent/KR840002357A/ko unknown
- 1982-11-09 AU AU90276/82A patent/AU9027682A/en not_active Abandoned
-
1984
- 1984-02-01 ES ES529349A patent/ES529349A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| PT75815A (en) | 1982-12-01 |
| GR78317B (xx) | 1984-09-26 |
| DK491582A (da) | 1983-05-10 |
| ES8500948A1 (es) | 1984-12-01 |
| NZ202404A (en) | 1985-11-08 |
| KR840002357A (ko) | 1984-06-25 |
| JPS5888364A (ja) | 1983-05-26 |
| EP0079556A2 (de) | 1983-05-25 |
| AU9027682A (en) | 1983-05-19 |
| PH18458A (en) | 1985-07-18 |
| ES8506635A1 (es) | 1985-08-01 |
| EP0079556A3 (de) | 1983-08-24 |
| FI823824A0 (fi) | 1982-11-08 |
| ES517222A0 (es) | 1984-12-01 |
| ZA827905B (en) | 1983-08-31 |
| US4374139A (en) | 1983-02-15 |
| HU187425B (en) | 1986-01-28 |
| FI823824L (fi) | 1983-05-10 |
| IL67180A0 (en) | 1983-03-31 |
| MC1490A1 (fr) | 1983-09-12 |
| ES529349A0 (es) | 1985-08-01 |
| PT75815B (en) | 1986-01-21 |
| CA1195324A (en) | 1985-10-15 |
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