CA1078385A - 1,4-ethano-6-oxo-octahydro-quinoline and 6-oxa-1-aza tricyclododecan-5-one compounds - Google Patents
1,4-ethano-6-oxo-octahydro-quinoline and 6-oxa-1-aza tricyclododecan-5-one compoundsInfo
- Publication number
- CA1078385A CA1078385A CA265,344A CA265344A CA1078385A CA 1078385 A CA1078385 A CA 1078385A CA 265344 A CA265344 A CA 265344A CA 1078385 A CA1078385 A CA 1078385A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- compound
- prepared
- diethyl
- ethyl
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 79
- ZQEXPTJDVNRSNX-UHFFFAOYSA-N 1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound O=C1CCC2C(C1)C1CCN2CC1 ZQEXPTJDVNRSNX-UHFFFAOYSA-N 0.000 title 1
- -1 isoalkyl Chemical group 0.000 claims abstract description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 71
- 239000002904 solvent Substances 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 21
- NHPWIWAGVOXDPU-UHFFFAOYSA-N 2-methylidene-1-azabicyclo[2.2.2]octan-3-one Chemical compound C1CC2CCN1C(=C)C2=O NHPWIWAGVOXDPU-UHFFFAOYSA-N 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 12
- 239000012279 sodium borohydride Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- MOWWNFWKBHOSHK-UHFFFAOYSA-N 4-phenyl-1-azatricyclo[6.2.2.02,7]dodec-6-en-5-one Chemical compound O=C1C=C2C(CC3)CCN3C2CC1C1=CC=CC=C1 MOWWNFWKBHOSHK-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- HENRHZYMIGNRQT-UHFFFAOYSA-N 4-ethyl-1-azatricyclo[6.2.2.02,7]dodec-6-en-5-one Chemical compound C1CC2C3=CC(=O)C(CC)CC3N1CC2 HENRHZYMIGNRQT-UHFFFAOYSA-N 0.000 claims description 3
- UYFSYIPAYQZXAY-UHFFFAOYSA-N 4-ethyl-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound C1CN2C3CC(CC)C(=O)CC3C1CC2 UYFSYIPAYQZXAY-UHFFFAOYSA-N 0.000 claims description 3
- 238000006114 decarboxylation reaction Methods 0.000 claims description 3
- MPQYWVGHMVTNAT-UHFFFAOYSA-N diethyl 2-methyl-2-[(3-oxo-1-azabicyclo[2.2.2]octan-2-yl)methyl]propanedioate Chemical compound C1CC2CCN1C(CC(C)(C(=O)OCC)C(=O)OCC)C2=O MPQYWVGHMVTNAT-UHFFFAOYSA-N 0.000 claims description 3
- UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 0.000 claims description 3
- 229940093858 ethyl acetoacetate Drugs 0.000 claims description 3
- ZQGWBPQBZHMUFG-UHFFFAOYSA-N 1,1-dimethylthiourea Chemical compound CN(C)C(N)=S ZQGWBPQBZHMUFG-UHFFFAOYSA-N 0.000 claims description 2
- RPNFNBGRHCUORR-UHFFFAOYSA-N diethyl 2-butylpropanedioate Chemical compound CCCCC(C(=O)OCC)C(=O)OCC RPNFNBGRHCUORR-UHFFFAOYSA-N 0.000 claims description 2
- VQAZCUCWHIIFGE-UHFFFAOYSA-N diethyl 2-ethylpropanedioate Chemical compound CCOC(=O)C(CC)C(=O)OCC VQAZCUCWHIIFGE-UHFFFAOYSA-N 0.000 claims description 2
- BYQFBFWERHXONI-UHFFFAOYSA-N diethyl 2-propan-2-ylpropanedioate Chemical compound CCOC(=O)C(C(C)C)C(=O)OCC BYQFBFWERHXONI-UHFFFAOYSA-N 0.000 claims description 2
- BTRGZBIXPLFVNK-UHFFFAOYSA-N ethyl 2-(4-methylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(C)C=C1 BTRGZBIXPLFVNK-UHFFFAOYSA-N 0.000 claims description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims description 2
- FLBXKBCYSKRFEN-UHFFFAOYSA-N hexahydro-7-phenyl-2h-1,4-ethanoquinolin-6(5h)-one Chemical compound O=C1CC2C(CC3)CCN3C2CC1C1=CC=CC=C1 FLBXKBCYSKRFEN-UHFFFAOYSA-N 0.000 claims description 2
- 229940049953 phenylacetate Drugs 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 20
- 238000006386 neutralization reaction Methods 0.000 claims 11
- 239000002253 acid Substances 0.000 claims 10
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 10
- 239000011707 mineral Substances 0.000 claims 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 150000002431 hydrogen Chemical group 0.000 claims 5
- GYUUWSJJZZQWKL-UHFFFAOYSA-N 4-(3-methoxyphenyl)-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound COC1=CC=CC(C2C(OC3C(N4CCC3CC4)C2)=O)=C1 GYUUWSJJZZQWKL-UHFFFAOYSA-N 0.000 claims 2
- GNFRLUHQTLGKCB-UHFFFAOYSA-N 4-butyl-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound C1CN2C3CC(CCCC)C(=O)OC3C1CC2 GNFRLUHQTLGKCB-UHFFFAOYSA-N 0.000 claims 2
- BMCPVCXIPPADKU-UHFFFAOYSA-N 4-ethyl-6-oxa-1-azatricyclo(4.2.2.0)dodecan-5-one Chemical compound C1CN2C3CC(CC)C(=O)OC3C1CC2 BMCPVCXIPPADKU-UHFFFAOYSA-N 0.000 claims 2
- CBEUWECWENHZBH-UHFFFAOYSA-N 4-methyl-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound C1CN2C3CC(C)C(=O)OC3C1CC2 CBEUWECWENHZBH-UHFFFAOYSA-N 0.000 claims 2
- IVFOTQIGNKKTDN-UHFFFAOYSA-N 4-phenyl-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound O=C1OC2C(CC3)CCN3C2CC1C1=CC=CC=C1 IVFOTQIGNKKTDN-UHFFFAOYSA-N 0.000 claims 2
- SOZUJRHLZQHNGO-UHFFFAOYSA-N 4-propan-2-yl-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound C1CN2C3CC(C(C)C)C(=O)OC3C1CC2 SOZUJRHLZQHNGO-UHFFFAOYSA-N 0.000 claims 2
- HGNBDTHHGQLHQL-UHFFFAOYSA-N 6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound C1CN2C3CCC(=O)OC3C1CC2 HGNBDTHHGQLHQL-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- NULOTIYTYAQOQC-UHFFFAOYSA-N ethyl 3-(3-hydroxy-1-azabicyclo[2.2.2]octan-2-yl)-2-phenylpropanoate Chemical compound OC1C(CC2)CCN2C1CC(C(=O)OCC)C1=CC=CC=C1 NULOTIYTYAQOQC-UHFFFAOYSA-N 0.000 claims 2
- YAFMQNKVUFXGKZ-UHFFFAOYSA-N ethyl 3-(3-oxo-1-azabicyclo[2.2.2]octan-2-yl)-2-phenylpropanoate Chemical compound C1CN2CCC1C(=O)C2CC(C(=O)OCC)C1=CC=CC=C1 YAFMQNKVUFXGKZ-UHFFFAOYSA-N 0.000 claims 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims 1
- MVKSOSWOFHOIEC-UHFFFAOYSA-N 4-benzyl-6-oxa-1-azatricyclo[6.2.2.02,7]dodecan-5-one Chemical compound O=C1OC2C(CC3)CCN3C2CC1CC1=CC=CC=C1 MVKSOSWOFHOIEC-UHFFFAOYSA-N 0.000 claims 1
- RQROWULDAJRGJP-UHFFFAOYSA-N 4-ethyl-1-azatricyclo[6.2.2.02,7]dodecan-5-one hydrochloride Chemical compound Cl.C1CN2C3CC(CC)C(=O)CC3C1CC2 RQROWULDAJRGJP-UHFFFAOYSA-N 0.000 claims 1
- PSSFYQXTZYNOKS-UHFFFAOYSA-N Cl.C1=CC(Cl)=CC=C1C1C(=O)OC(C2CCN3CC2)C3C1 Chemical compound Cl.C1=CC(Cl)=CC=C1C1C(=O)OC(C2CCN3CC2)C3C1 PSSFYQXTZYNOKS-UHFFFAOYSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 claims 1
- FCRMRZRBCAEBDB-UHFFFAOYSA-N ctk2f0589 Chemical compound Cl.O=C1CC2C(CC3)CCN3C2CC1C1=CC=CC=C1 FCRMRZRBCAEBDB-UHFFFAOYSA-N 0.000 claims 1
- XXVVNHCWPHMLEZ-UHFFFAOYSA-N ethyl 2-(3-methoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(OC)=C1 XXVVNHCWPHMLEZ-UHFFFAOYSA-N 0.000 claims 1
- UTWBWFXECVFDPZ-UHFFFAOYSA-N ethyl 2-(4-chlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(Cl)C=C1 UTWBWFXECVFDPZ-UHFFFAOYSA-N 0.000 claims 1
- OKANYBNORCUPKZ-UHFFFAOYSA-N ethyl 2-ethyl-3-oxobutanoate Chemical compound CCOC(=O)C(CC)C(C)=O OKANYBNORCUPKZ-UHFFFAOYSA-N 0.000 claims 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 3
- 239000000021 stimulant Substances 0.000 abstract description 3
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 3
- 206010020651 Hyperkinesia Diseases 0.000 abstract description 2
- 208000000269 Hyperkinesis Diseases 0.000 abstract description 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 239000002637 mydriatic agent Substances 0.000 abstract description 2
- 230000002911 mydriatic effect Effects 0.000 abstract description 2
- 201000003631 narcolepsy Diseases 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000000391 smoking effect Effects 0.000 abstract description 2
- 201000003152 motion sickness Diseases 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- DOXYUCZSYSEALW-UHFFFAOYSA-N dodecan-5-one Chemical compound CCCCCCCC(=O)CCCC DOXYUCZSYSEALW-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 229960001701 chloroform Drugs 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 229930003347 Atropine Natural products 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 4
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 4
- 229960000396 atropine Drugs 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 230000002093 peripheral effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
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- VZYFATPWYBVSAL-UHFFFAOYSA-N 2-methylidene-1-azabicyclo[2.2.2]octane Chemical compound C1CN2C(=C)CC1CC2 VZYFATPWYBVSAL-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- GRRSDGHTSMJICM-UHFFFAOYSA-N diethyl 2-propylpropanedioate Chemical compound CCOC(=O)C(CCC)C(=O)OCC GRRSDGHTSMJICM-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- CLAGTHFERAFBDI-UHFFFAOYSA-N dodecan-5-one;hydrochloride Chemical compound Cl.CCCCCCCC(=O)CCCC CLAGTHFERAFBDI-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 201000003102 mental depression Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 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
- 239000012452 mother liquor Substances 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000037047 psychomotor activity Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical class [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 210000002222 superior cervical ganglion Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Addiction (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL48453A IL48453A (en) | 1975-11-11 | 1975-11-11 | Substituted 6-oxa-1-azatricyclo-(6.2.2.0 )dodecan-5-ones and 1,4-ethano-5-oxo octa (or decahydro)quinoline,their preparation and pharmaceutical compositions containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1078385A true CA1078385A (en) | 1980-05-27 |
Family
ID=11048546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA265,344A Expired CA1078385A (en) | 1975-11-11 | 1976-11-10 | 1,4-ethano-6-oxo-octahydro-quinoline and 6-oxa-1-aza tricyclododecan-5-one compounds |
Country Status (22)
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4183938A (en) * | 1975-11-11 | 1980-01-15 | The Purdue Frederick Company | 1,8-Ethano-5-oxo-octa- and -decahydroquinolines and mydriatic compositions thereof |
| US4855290A (en) | 1985-05-10 | 1989-08-08 | State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research | Derivatives of quinuclidine |
| US4876260A (en) * | 1987-10-28 | 1989-10-24 | State Of Israel, Israel Institute Of Biological Research | Oxathiolanes |
| JPH0523864Y2 (US20020051482A1-20020502-M00012.png) * | 1989-09-05 | 1993-06-17 | ||
| US5407938A (en) * | 1990-04-10 | 1995-04-18 | Israel Institute For Biological Research | Certain 1-methyl-piperidine-4-spiro-4'-(1'-3'-oxazolines) and corresponding -(1',3' thiazolines) |
| US5852029A (en) * | 1990-04-10 | 1998-12-22 | Israel Institute For Biological Research | Aza spiro compounds acting on the cholinergic system with muscarinic agonist activity |
| JPH0518551U (ja) * | 1991-08-28 | 1993-03-09 | 亀吉 立花 | ぶら下がり健康器 |
| US5521193A (en) * | 1992-06-24 | 1996-05-28 | G. D. Searle & Co. | Benzimidazole compounds |
| US5280028A (en) * | 1992-06-24 | 1994-01-18 | G. D. Searle & Co. | Benzimidazole compounds |
| US5534521A (en) * | 1993-06-23 | 1996-07-09 | G. D. Searle & Co. | Benzimidazole compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3857837A (en) * | 1968-07-02 | 1974-12-31 | Hoffmann La Roche | Processes and intermediated for quinine, quinidine, isomers and derivatives thereof |
-
1975
- 1975-11-11 IL IL48453A patent/IL48453A/xx unknown
-
1976
- 1976-02-06 US US05/655,650 patent/US4083985A/en not_active Expired - Lifetime
- 1976-10-28 AR AR265267A patent/AR213184A1/es active
- 1976-11-03 FI FI763152A patent/FI60013C/fi not_active IP Right Cessation
- 1976-11-06 DE DE19762650876 patent/DE2650876A1/de not_active Ceased
- 1976-11-08 NZ NZ182556A patent/NZ182556A/xx unknown
- 1976-11-08 ZA ZA766663A patent/ZA766663B/xx unknown
- 1976-11-09 NL NL7612427A patent/NL7612427A/xx not_active Application Discontinuation
- 1976-11-10 GB GB46748/76A patent/GB1571511A/en not_active Expired
- 1976-11-10 IN IN2028/CAL/1976A patent/IN145202B/en unknown
- 1976-11-10 NO NO763820A patent/NO144927C/no unknown
- 1976-11-10 CA CA265,344A patent/CA1078385A/en not_active Expired
- 1976-11-10 BE BE172272A patent/BE848227A/xx not_active IP Right Cessation
- 1976-11-10 DK DK507376A patent/DK507376A/da not_active Application Discontinuation
- 1976-11-10 CH CH1417776A patent/CH635102A5/de not_active IP Right Cessation
- 1976-11-10 FR FR7634034A patent/FR2331339A1/fr active Granted
- 1976-11-10 ES ES453162A patent/ES453162A1/es not_active Expired
- 1976-11-11 JP JP51136167A patent/JPS6045198B2/ja not_active Expired
- 1976-11-11 MX MX765119U patent/MX4767E/es unknown
- 1976-11-11 AT AT839476A patent/AT355035B/de not_active IP Right Cessation
- 1976-11-11 AU AU19552/76A patent/AU511347B2/en not_active Expired
-
1980
- 1980-05-05 SE SE8003351A patent/SE435929B/sv not_active IP Right Cessation
-
1982
- 1982-04-30 CH CH267282A patent/CH640234A5/de not_active IP Right Cessation
-
1984
- 1984-08-10 JP JP59166668A patent/JPS6043348B2/ja not_active Expired
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |