NO753062L - - Google Patents
Info
- Publication number
- NO753062L NO753062L NO753062A NO753062A NO753062L NO 753062 L NO753062 L NO 753062L NO 753062 A NO753062 A NO 753062A NO 753062 A NO753062 A NO 753062A NO 753062 L NO753062 L NO 753062L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- cis
- well
- acceptable salts
- compound
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 238000010992 reflux Methods 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 7
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 7
- QTJVCDNDJFHYIR-VWNXMTODSA-N (4aR,8aS)-4a-(3-methoxyphenyl)-2-(2-phenylethyl)-1,3,4,5,6,7,8,8a-octahydroisoquinoline Chemical group C1(=CC=CC=C1)CCN1C[C@H]2CCCC[C@]2(CC1)C1=CC(=CC=C1)OC QTJVCDNDJFHYIR-VWNXMTODSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- RZQYAGNFCZDLPG-GGAORHGYSA-N 3-[(4aR,8aS)-2-(2-phenylethyl)-1,3,4,5,6,7,8,8a-octahydroisoquinolin-4a-yl]phenol Chemical group C1(=CC=CC=C1)CCN1C[C@H]2CCCC[C@]2(CC1)C1=CC(=CC=C1)O RZQYAGNFCZDLPG-GGAORHGYSA-N 0.000 claims description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 231100000241 scar Toxicity 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- MRCIZXDLCLSQSU-QUCCMNQESA-N (4aR,8aS)-2-(cyclopropylmethyl)-4a-(3-methoxyphenyl)-1,3,4,5,6,7,8,8a-octahydroisoquinoline Chemical group C1(CC1)CN1C[C@H]2CCCC[C@]2(CC1)C1=CC(=CC=C1)OC MRCIZXDLCLSQSU-QUCCMNQESA-N 0.000 claims 1
- ZMMPBZMELZHMIT-ZBFHGGJFSA-N 3-[(4aR,8aS)-2-methyl-1,3,4,5,6,7,8,8a-octahydroisoquinolin-4a-yl]phenol Chemical group CN1C[C@H]2CCCC[C@]2(CC1)C1=CC(=CC=C1)O ZMMPBZMELZHMIT-ZBFHGGJFSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 241000208202 Linaceae Species 0.000 claims 1
- 235000004431 Linum usitatissimum Nutrition 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000000047 product Substances 0.000 description 40
- 239000000203 mixture Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000003921 oil Substances 0.000 description 23
- 235000019198 oils Nutrition 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- 239000012259 ether extract Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- CCHNWURRBFGQCD-UHFFFAOYSA-N 2-chlorocyclohexan-1-one Chemical compound ClC1CCCCC1=O CCHNWURRBFGQCD-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 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
- 239000002552 dosage form Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- DUOKTVFXVRZKOJ-UHFFFAOYSA-N ethyl 2-(2-cyano-1-phenylcyclohex-2-en-1-yl)acetate Chemical compound C=1C=CC=CC=1C1(CC(=O)OCC)CCCC=C1C#N DUOKTVFXVRZKOJ-UHFFFAOYSA-N 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 3
- AYKOCNRDYSODOJ-BBRMVZONSA-N (4ar,8ar)-2-methyl-4a-phenyl-4,5,6,7,8,8a-hexahydroisoquinoline-1,3-dione Chemical compound C1([C@]23CC(=O)N(C([C@@H]2CCCC3)=O)C)=CC=CC=C1 AYKOCNRDYSODOJ-BBRMVZONSA-N 0.000 description 2
- MEUQJLPINLZBFO-BBRMVZONSA-N (4ar,8ar)-4a-(3-methoxyphenyl)-4,5,6,7,8,8a-hexahydroisoquinoline-1,3-dione Chemical compound COC1=CC=CC([C@]23[C@@H](CCCC2)C(=O)NC(=O)C3)=C1 MEUQJLPINLZBFO-BBRMVZONSA-N 0.000 description 2
- ZVUPIZCQKCQXCR-CVEARBPZSA-N (4ar,8as)-2-methyl-4a-phenyl-1,3,4,5,6,7,8,8a-octahydroisoquinoline Chemical compound C1([C@]23CCN(C[C@H]2CCCC3)C)=CC=CC=C1 ZVUPIZCQKCQXCR-CVEARBPZSA-N 0.000 description 2
- NDEBTTKKQOYLNO-WBVHZDCISA-N (4ar,8as)-4a-(3-methoxyphenyl)-2-methyl-1,3,4,5,6,7,8,8a-octahydroisoquinoline Chemical compound COC1=CC=CC([C@]23[C@H](CCCC2)CN(C)CC3)=C1 NDEBTTKKQOYLNO-WBVHZDCISA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-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
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000001916 cyano esters Chemical class 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- XBMJPPLETQINDG-UHFFFAOYSA-N ethyl 2-(2-oxo-1-phenylcyclohexyl)acetate Chemical compound C=1C=CC=CC=1C1(CC(=O)OCC)CCCCC1=O XBMJPPLETQINDG-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 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
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography 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
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- GHCJLQGFFNKTCD-YOEHRIQHSA-N (4ar,8ar)-4a-(3-methoxyphenyl)-2-methyl-4,5,6,7,8,8a-hexahydroisoquinoline-1,3-dione Chemical compound COC1=CC=CC([C@]23[C@@H](CCCC2)C(=O)N(C)C(=O)C3)=C1 GHCJLQGFFNKTCD-YOEHRIQHSA-N 0.000 description 1
- GHCJLQGFFNKTCD-PBHICJAKSA-N (4ar,8as)-4a-(3-methoxyphenyl)-2-methyl-4,5,6,7,8,8a-hexahydroisoquinoline-1,3-dione Chemical compound COC1=CC=CC([C@]23[C@H](CCCC2)C(=O)N(C)C(=O)C3)=C1 GHCJLQGFFNKTCD-PBHICJAKSA-N 0.000 description 1
- NENLYAQPNATJSU-IUCAKERBSA-N (4as,8ar)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical group C1NCC[C@@H]2CCCC[C@H]21 NENLYAQPNATJSU-IUCAKERBSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- LRGZZEOWQURWFK-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydroisoquinoline Chemical compound C1NCCC2CCCC=C21 LRGZZEOWQURWFK-UHFFFAOYSA-N 0.000 description 1
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- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/687—Unsaturated compounds containing a keto groups being part of a ring containing halogen
- C07C49/697—Unsaturated compounds containing a keto groups being part of a ring containing halogen containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen 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)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO762292A NO762292L (ko) | 1974-09-09 | 1976-07-01 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50430274A | 1974-09-09 | 1974-09-09 | |
| US59946175A | 1975-08-01 | 1975-08-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO753062L true NO753062L (ko) | 1976-03-10 |
Family
ID=27054787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO753062A NO753062L (ko) | 1974-09-09 | 1975-09-08 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4150135A (ko) |
| JP (1) | JPS5154572A (ko) |
| AR (1) | AR208562A1 (ko) |
| AU (1) | AU503631B2 (ko) |
| BE (1) | BE833212A (ko) |
| DD (1) | DD123190A5 (ko) |
| DE (1) | DE2539907A1 (ko) |
| DK (1) | DK401575A (ko) |
| ES (2) | ES440830A1 (ko) |
| FI (1) | FI752516A (ko) |
| FR (2) | FR2283681A1 (ko) |
| GB (1) | GB1484431A (ko) |
| IE (1) | IE41898B1 (ko) |
| IL (1) | IL48061A (ko) |
| LU (1) | LU73348A1 (ko) |
| NL (1) | NL7510617A (ko) |
| NO (1) | NO753062L (ko) |
| SE (1) | SE7509022L (ko) |
| SU (1) | SU682126A3 (ko) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4419517A (en) * | 1973-06-01 | 1983-12-06 | E. I. Du Pont De Nemours & Co. | 4a-Aryl-trans-decahydroisoquinolines |
| US4219652A (en) * | 1975-09-30 | 1980-08-26 | Eli Lilly And Company | N-Methyl and N-phenethyl-cis-decahydroisoquinolines |
| US4301290A (en) * | 1975-12-16 | 1981-11-17 | Sandoz Ltd. | Organic compounds |
| DE2636684C3 (de) * | 1976-08-14 | 1980-06-19 | Merck Patent Gmbh, 6100 Darmstadt | Phenylcyclohexanderivate und ihre Verwendung in flüssigkristallinen Dielektrika |
| DE2702598C2 (de) * | 1977-01-22 | 1984-10-25 | Merck Patent Gmbh, 6100 Darmstadt | Cyclohexylcyclohexane und diese enthaltende Dielektrika |
| US4118386A (en) * | 1977-04-04 | 1978-10-03 | Hoffmann-La Roche Inc. | Synthesis of imidazo[1,5-a]diazepine-3-carboxylates |
| US4289882A (en) | 1978-04-26 | 1981-09-15 | The United States Of America As Represented By The Department Of Health & Human Services | 4A-Aryl-decahydroisoquinolines |
| JPS57122041A (en) * | 1981-01-21 | 1982-07-29 | Suntory Ltd | Phenylclohexane derivative |
| US4349677A (en) * | 1981-11-09 | 1982-09-14 | Morton-Norwich Products, Inc. | 3,4-Dihydro-3,4-isoquinolinedione 4-oxime |
| US4537963A (en) * | 1981-12-28 | 1985-08-27 | E. I. Du Pont De Nemours And Company | Intermediates for octahydrobenzofuro[3,2-E]isoquinolines |
| US4579952A (en) * | 1981-12-28 | 1986-04-01 | E. I. Du Pont De Nemours And Company | Intermediates for octahydrobenzofuro[3,2-e]isoquinolines |
| US4421916A (en) * | 1981-12-28 | 1983-12-20 | E. I. Du Pont De Nemours & Co. | Intermediates for octahydrobenzofuro[3,2-e]isoquinolines |
| IT1307327B1 (it) * | 1995-09-12 | 2001-10-30 | Smithkline Beecham Spa | Derivati idroisochinolinici sostituiti |
| CN105473554B (zh) | 2013-07-10 | 2019-08-13 | 沃泰克斯药物股份有限公司 | 作为离子通道调节剂的稠合的哌啶酰胺类 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2740788A (en) * | 1956-04-03 | J-hydroxy-n-propargyl-morphinanes | ||
| DE1670694B2 (de) | 1966-05-05 | 1976-07-22 | Hoechst Ag, 6000 Frankfurt | Verfahren zur herstellung von tetrahydroisochinolinen |
| US3546227A (en) * | 1966-12-01 | 1970-12-08 | Sandoz Ag | 2,3-dihydro-1h-benz(d,e)isoquinoline carboxamidines |
| US3666763A (en) * | 1970-01-06 | 1972-05-30 | Hoffmann La Roche | 4-phenyl isoquinolines and process for preparing same |
| ZA734895B (en) * | 1972-07-20 | 1974-06-26 | Du Pont | Analgesigs and/or narcotic antagonists |
-
1975
- 1975-08-12 SE SE7509022A patent/SE7509022L/xx unknown
- 1975-09-05 IL IL48061A patent/IL48061A/xx unknown
- 1975-09-08 DE DE19752539907 patent/DE2539907A1/de not_active Withdrawn
- 1975-09-08 LU LU73348A patent/LU73348A1/xx unknown
- 1975-09-08 GB GB36885/75A patent/GB1484431A/en not_active Expired
- 1975-09-08 SU SU752169463A patent/SU682126A3/ru active
- 1975-09-08 DD DD188238A patent/DD123190A5/xx unknown
- 1975-09-08 NO NO753062A patent/NO753062L/no unknown
- 1975-09-08 AU AU84608/75A patent/AU503631B2/en not_active Expired
- 1975-09-08 FI FI752516A patent/FI752516A/fi not_active Application Discontinuation
- 1975-09-08 DK DK401575A patent/DK401575A/da not_active Application Discontinuation
- 1975-09-09 FR FR7527562A patent/FR2283681A1/fr not_active Withdrawn
- 1975-09-09 NL NL7510617A patent/NL7510617A/xx not_active Application Discontinuation
- 1975-09-09 AR AR260314A patent/AR208562A1/es active
- 1975-09-09 BE BE159859A patent/BE833212A/xx unknown
- 1975-09-09 ES ES440830A patent/ES440830A1/es not_active Expired
- 1975-09-09 IE IE1959/75A patent/IE41898B1/en unknown
- 1975-09-09 JP JP50109420A patent/JPS5154572A/ja active Pending
-
1976
- 1976-06-03 FR FR7616802A patent/FR2309536A1/fr active Granted
-
1977
- 1977-02-22 ES ES456168A patent/ES456168A1/es not_active Expired
- 1977-03-04 US US05/774,436 patent/US4150135A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| FR2283681A1 (fr) | 1976-04-02 |
| JPS5154572A (en) | 1976-05-13 |
| FI752516A (ko) | 1976-03-10 |
| DD123190A5 (ko) | 1976-12-05 |
| IE41898B1 (en) | 1980-04-23 |
| LU73348A1 (ko) | 1976-08-13 |
| IE41898L (en) | 1976-03-09 |
| NL7510617A (nl) | 1976-03-11 |
| DE2539907A1 (de) | 1976-03-25 |
| DK401575A (da) | 1976-03-10 |
| AR208562A1 (es) | 1977-02-15 |
| ES440830A1 (es) | 1977-07-01 |
| US4150135A (en) | 1979-04-17 |
| AU503631B2 (en) | 1979-09-13 |
| BE833212A (fr) | 1976-03-09 |
| SU682126A3 (ru) | 1979-08-25 |
| IL48061A (en) | 1979-09-30 |
| ES456168A1 (es) | 1978-08-01 |
| AU8460875A (en) | 1977-03-17 |
| IL48061A0 (en) | 1975-11-25 |
| FR2309536B1 (ko) | 1979-07-27 |
| GB1484431A (en) | 1977-09-01 |
| FR2309536A1 (fr) | 1976-11-26 |
| SE7509022L (sv) | 1976-03-10 |
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