CA2243243A1 - Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser - Google Patents
Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser Download PDFInfo
- Publication number
- CA2243243A1 CA2243243A1 CA 2243243 CA2243243A CA2243243A1 CA 2243243 A1 CA2243243 A1 CA 2243243A1 CA 2243243 CA2243243 CA 2243243 CA 2243243 A CA2243243 A CA 2243243A CA 2243243 A1 CA2243243 A1 CA 2243243A1
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- CA
- Canada
- Prior art keywords
- methyl
- amino
- hydrogen
- mmol
- formula
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 42
- JRZGPXSSNPTNMA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-1-amine Chemical class C1=CC=C2C(N)CCCC2=C1 JRZGPXSSNPTNMA-UHFFFAOYSA-N 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 title description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 28
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
- 150000002367 halogens Chemical group 0.000 claims abstract description 24
- 208000016285 Movement disease Diseases 0.000 claims abstract description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 12
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical group 0.000 claims abstract 14
- 150000001875 compounds Chemical class 0.000 claims description 109
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- -1 bromo, methoxy, ethoxy Chemical group 0.000 claims description 22
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- PMZSOOOPRABQMS-FVGYRXGTSA-N (2s)-5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C2=C1C[C@@H](NC)CC2 PMZSOOOPRABQMS-FVGYRXGTSA-N 0.000 claims description 6
- WWRJRKPCRXJACI-JTQLQIEISA-N (2s)-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=CC(OC)=C2C[C@@H](NC)CCC2=C1 WWRJRKPCRXJACI-JTQLQIEISA-N 0.000 claims description 6
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
- ZSIAKNKANPQFTH-PPHPATTJSA-N (2s)-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2C[C@@H](NC)CCC2=C1 ZSIAKNKANPQFTH-PPHPATTJSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003981 vehicle Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- PMZSOOOPRABQMS-UHFFFAOYSA-N 5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C2=C1CC(NC)CC2 PMZSOOOPRABQMS-UHFFFAOYSA-N 0.000 claims description 3
- BJFHJWRQUZEHRE-UHFFFAOYSA-N 6-bromo-5,8-dimethoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.COC1=CC(Br)=C(OC)C2=C1CC(NC)CC2 BJFHJWRQUZEHRE-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- CKXFPBHAUKEBBF-UHFFFAOYSA-N n-ethyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NCC)CCC2=C1OC CKXFPBHAUKEBBF-UHFFFAOYSA-N 0.000 claims description 3
- CKXFPBHAUKEBBF-PPHPATTJSA-N (2s)-n-ethyl-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2C[C@@H](NCC)CCC2=C1OC CKXFPBHAUKEBBF-PPHPATTJSA-N 0.000 claims description 2
- AAFPRLDUYSCCGD-UHFFFAOYSA-N 5-bromo-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NC)CCC2=C1Br AAFPRLDUYSCCGD-UHFFFAOYSA-N 0.000 claims description 2
- LYMDZJCFPOOCBO-UHFFFAOYSA-N 5-ethoxy-8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1C(NC)CCC2=C1C(OC)=CC=C2OCC LYMDZJCFPOOCBO-UHFFFAOYSA-N 0.000 claims description 2
- ZSIAKNKANPQFTH-UHFFFAOYSA-N 8-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(NC)CCC2=C1 ZSIAKNKANPQFTH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 121
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- 239000000243 solution Substances 0.000 description 69
- 239000002904 solvent Substances 0.000 description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000000741 silica gel Substances 0.000 description 45
- 229910002027 silica gel Inorganic materials 0.000 description 45
- 229960001866 silicon dioxide Drugs 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 239000007787 solid Substances 0.000 description 40
- 229910001868 water Inorganic materials 0.000 description 39
- 238000001914 filtration Methods 0.000 description 33
- 239000000463 material Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 239000003921 oil Substances 0.000 description 26
- 235000019198 oils Nutrition 0.000 description 26
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 24
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 208000012661 Dyskinesia Diseases 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 238000012360 testing method Methods 0.000 description 19
- 241000282693 Cercopithecidae Species 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 239000003176 neuroleptic agent Substances 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- 241000282668 Cebus Species 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000001035 drying Methods 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 230000000142 dyskinetic effect Effects 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910000085 borane Inorganic materials 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 12
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000009835 boiling Methods 0.000 description 11
- 229960003878 haloperidol Drugs 0.000 description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
- 238000000023 Kugelrohr distillation Methods 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000002024 ethyl acetate extract Substances 0.000 description 10
- 239000011630 iodine Substances 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 208000015592 Involuntary movements Diseases 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- LCGFVWKNXLRFIF-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-2-amine Chemical class C1=CC=C2CC(N)CCC2=C1 LCGFVWKNXLRFIF-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 208000010118 dystonia Diseases 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 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
- 238000002360 preparation method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 206010008748 Chorea Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 5
- 239000003377 acid catalyst Substances 0.000 description 5
- 229960004046 apomorphine Drugs 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000012259 ether extract Substances 0.000 description 5
- 238000003810 ethyl acetate extraction Methods 0.000 description 5
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- 239000010410 layer Substances 0.000 description 5
- KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
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- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
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- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
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- MURVUTUZSUEIGI-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(Br)C(CBr)=C1 MURVUTUZSUEIGI-UHFFFAOYSA-N 0.000 description 2
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- ZJYJZEAJZXVAMF-UHFFFAOYSA-N 2-nitronaphthalene Chemical compound C1=CC=CC2=CC([N+](=O)[O-])=CC=C21 ZJYJZEAJZXVAMF-UHFFFAOYSA-N 0.000 description 2
- BENQALZXOPIFJI-UHFFFAOYSA-N 5-ethoxy-8-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C(N)CCC2=C1C(OC)=CC=C2OCC BENQALZXOPIFJI-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- XRVNUXUNETXLEU-UHFFFAOYSA-N 7-bromo-5,8-dimethoxy-1,2-dihydronaphthalene Chemical compound C1CC=CC2=C1C(OC)=C(Br)C=C2OC XRVNUXUNETXLEU-UHFFFAOYSA-N 0.000 description 2
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- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
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- 238000000227 grinding Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000009815 homocoupling reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 229930189585 ingamine Natural products 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- HAPIWIKECFVQBM-UHFFFAOYSA-N n-(7-bromo-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)formamide Chemical compound C1C(NC=O)CCC2=C1C(OC)=C(Br)C=C2OC HAPIWIKECFVQBM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000005371 pilomotor reflex Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003491 tear gas Substances 0.000 description 1
- 125000004862 thiobutyl group Chemical group 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000007514 turning Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002569 water oil cream Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1264096P | 1996-03-01 | 1996-03-01 | |
| US60/012,640 | 1996-03-01 | ||
| PCT/GB1997/000516 WO1997031887A1 (fr) | 1996-03-01 | 1997-02-25 | Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2243243A1 true CA2243243A1 (fr) | 1997-09-04 |
Family
ID=29422184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2243243 Abandoned CA2243243A1 (fr) | 1996-03-01 | 1997-02-25 | Derives de l'aminotetraline, compositions contenant ces derives et methodes pour les utiliser |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2243243A1 (fr) |
-
1997
- 1997-02-25 CA CA 2243243 patent/CA2243243A1/fr not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Dead |