NL8105170A - Nieuwe fenylalkylaminen, werkwijze ter bereiding daarvan en de toepassing daarvan als geneesmiddelen. - Google Patents
Nieuwe fenylalkylaminen, werkwijze ter bereiding daarvan en de toepassing daarvan als geneesmiddelen. Download PDFInfo
- Publication number
- NL8105170A NL8105170A NL8105170A NL8105170A NL8105170A NL 8105170 A NL8105170 A NL 8105170A NL 8105170 A NL8105170 A NL 8105170A NL 8105170 A NL8105170 A NL 8105170A NL 8105170 A NL8105170 A NL 8105170A
- Authority
- NL
- Netherlands
- Prior art keywords
- group
- amino
- carbon atoms
- ethanol
- propyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 17
- 238000000034 method Methods 0.000 title claims description 9
- 239000003814 drug Substances 0.000 title claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 title description 2
- -1 hydroxymethylene group Chemical group 0.000 claims description 719
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 718
- 125000004432 carbon atom Chemical group C* 0.000 claims description 102
- 150000001875 compounds Chemical class 0.000 claims description 66
- 239000000460 chlorine Substances 0.000 claims description 57
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 45
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000003277 amino group Chemical group 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 235000005985 organic acids Nutrition 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 5
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 238000003776 cleavage reaction Methods 0.000 claims description 5
- 230000001681 protective effect Effects 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 241001331845 Equus asinus x caballus Species 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 519
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 254
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 138
- 238000002329 infrared spectrum Methods 0.000 description 136
- 239000012279 sodium borohydride Substances 0.000 description 113
- 229910000033 sodium borohydride Inorganic materials 0.000 description 113
- 238000002211 ultraviolet spectrum Methods 0.000 description 109
- 239000003921 oil Substances 0.000 description 103
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 95
- 238000002844 melting Methods 0.000 description 82
- 230000008018 melting Effects 0.000 description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 68
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 61
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 46
- 239000012280 lithium aluminium hydride Substances 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 37
- 239000002904 solvent Substances 0.000 description 35
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 30
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 26
- 229960004592 isopropanol Drugs 0.000 description 23
- 238000001704 evaporation Methods 0.000 description 22
- 238000001228 spectrum Methods 0.000 description 22
- 239000003480 eluent Substances 0.000 description 21
- 230000008020 evaporation Effects 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- 235000011121 sodium hydroxide Nutrition 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 229940086542 triethylamine Drugs 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 125000001931 aliphatic group Chemical group 0.000 description 12
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 11
- 229930040373 Paraformaldehyde Natural products 0.000 description 11
- 229910021529 ammonia Inorganic materials 0.000 description 11
- 238000009835 boiling Methods 0.000 description 11
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229920002866 paraformaldehyde Polymers 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- NUZDQSUVPDNSSJ-UHFFFAOYSA-N 3-(4-methoxyphenyl)propan-1-amine Chemical group COC1=CC=C(CCCN)C=C1 NUZDQSUVPDNSSJ-UHFFFAOYSA-N 0.000 description 7
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 7
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000000052 vinegar Substances 0.000 description 7
- 235000021419 vinegar Nutrition 0.000 description 7
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- 239000000284 extract Substances 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- IKYFHRVPKIFGMH-UHFFFAOYSA-N 1-phenoxypropan-2-amine Chemical compound CC(N)COC1=CC=CC=C1 IKYFHRVPKIFGMH-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 229910052987 metal hydride Inorganic materials 0.000 description 5
- 150000004681 metal hydrides Chemical class 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000005245 sintering Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 4
- IRYPMKXHLFMIBU-UHFFFAOYSA-N 4-(4-methoxyphenyl)-n-methylbutan-1-amine Chemical compound CNCCCCC1=CC=C(OC)C=C1 IRYPMKXHLFMIBU-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
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- 150000007513 acids Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical class [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- ZJRCIQAMTAINCB-UHFFFAOYSA-N benzoylacetonitrile Chemical compound N#CCC(=O)C1=CC=CC=C1 ZJRCIQAMTAINCB-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000004651 carbonic acid esters Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 108700041286 delta Proteins 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
- 238000002955 isolation Methods 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000006629 isopropoxycarbonylamino group Chemical group 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- XKHCUFJKGWJLNO-UHFFFAOYSA-N methyl(3-phenylpropyl)azanium;chloride Chemical compound [Cl-].C[NH2+]CCCC1=CC=CC=C1 XKHCUFJKGWJLNO-UHFFFAOYSA-N 0.000 description 1
- FYAKVMJQKATGHX-UHFFFAOYSA-N methyl-[3-(4-phenylmethoxyphenyl)propyl]azanium;chloride Chemical compound [Cl-].C1=CC(CCC[NH2+]C)=CC=C1OCC1=CC=CC=C1 FYAKVMJQKATGHX-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- BBHFXHDPZONCIV-UHFFFAOYSA-N n-cyclopropyl-2-phenylacetamide Chemical compound C1CC1NC(=O)CC1=CC=CC=C1 BBHFXHDPZONCIV-UHFFFAOYSA-N 0.000 description 1
- XSGSTHQZHRLSHO-UHFFFAOYSA-N n-ethyl-2-(4-methoxyphenyl)ethanamine Chemical compound CCNCCC1=CC=C(OC)C=C1 XSGSTHQZHRLSHO-UHFFFAOYSA-N 0.000 description 1
- NKESEILLNJNNMO-UHFFFAOYSA-N n-methyl-3-(4-phenylmethoxyphenyl)propan-1-amine Chemical compound C1=CC(CCCNC)=CC=C1OCC1=CC=CC=C1 NKESEILLNJNNMO-UHFFFAOYSA-N 0.000 description 1
- JBIKEQDMJSSOEM-UHFFFAOYSA-N n-propan-2-ylpropan-1-amine;hydrochloride Chemical compound Cl.CCCNC(C)C JBIKEQDMJSSOEM-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 229940113115 polyethylene glycol 200 Drugs 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000000075 primary alcohol group Chemical group 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
- G11B23/00—Record carriers not specific to the method of recording or reproducing; Accessories, e.g. containers, specially adapted for co-operation with the recording or reproducing apparatus ; Intermediate mediums; Apparatus or processes specially adapted for their manufacture
- G11B23/02—Containers; Storing means both adapted to cooperate with the recording or reproducing means
- G11B23/04—Magazines; Cassettes for webs or filaments
- G11B23/08—Magazines; Cassettes for webs or filaments for housing webs or filaments having two distinct ends
- G11B23/087—Magazines; Cassettes for webs or filaments for housing webs or filaments having two distinct ends using two different reels or cores
-
- G—PHYSICS
- G11—INFORMATION STORAGE
- G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
- G11B25/00—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus
- G11B25/06—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus using web-form record carriers, e.g. tape
- G11B25/066—Apparatus characterised by the shape of record carrier employed but not specific to the method of recording or reproducing, e.g. dictating apparatus; Combinations of such apparatus using web-form record carriers, e.g. tape adapted for use with containers of different sizes or configurations; adaptor devices therefor
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3046465 | 1980-12-10 | ||
| DE3046465 | 1980-12-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8105170A true NL8105170A (nl) | 1982-07-01 |
Family
ID=6118763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8105170A NL8105170A (nl) | 1980-12-10 | 1981-11-16 | Nieuwe fenylalkylaminen, werkwijze ter bereiding daarvan en de toepassing daarvan als geneesmiddelen. |
Country Status (32)
| Country | Link |
|---|---|
| JP (1) | JPS57122048A (es) |
| KR (1) | KR870000183B1 (es) |
| AR (1) | AR227802A1 (es) |
| AT (1) | AT379378B (es) |
| AU (1) | AU547655B2 (es) |
| BE (1) | BE891416A (es) |
| CA (1) | CA1202636A (es) |
| CH (1) | CH651541A5 (es) |
| CS (1) | CS229924B2 (es) |
| DD (1) | DD202867A5 (es) |
| DE (1) | DE3146623A1 (es) |
| DK (1) | DK541981A (es) |
| ES (4) | ES8301890A1 (es) |
| FI (1) | FI813934L (es) |
| FR (1) | FR2498596B1 (es) |
| GB (1) | GB2088873B (es) |
| GR (1) | GR77323B (es) |
| HU (1) | HU185676B (es) |
| IE (1) | IE52007B1 (es) |
| IL (1) | IL64498A (es) |
| IT (1) | IT1172129B (es) |
| LU (1) | LU83830A1 (es) |
| NL (1) | NL8105170A (es) |
| NO (1) | NO152649C (es) |
| NZ (1) | NZ199215A (es) |
| PH (1) | PH21599A (es) |
| PL (1) | PL129385B1 (es) |
| PT (1) | PT74112B (es) |
| SE (1) | SE8107387L (es) |
| SU (1) | SU1172449A3 (es) |
| YU (1) | YU290381A (es) |
| ZA (1) | ZA818529B (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4720586A (en) * | 1983-12-06 | 1988-01-19 | Fisons, Plc | Substituted 3,4-dihydroxy-phenylethylamino compounds |
| GB8419963D0 (en) * | 1984-08-06 | 1984-09-12 | Lundbeck & Co As H | Intermediate compound and method |
| US4943591A (en) * | 1984-10-17 | 1990-07-24 | Glaxo Group Limited | Dichloroaniline derivatives |
| GB8426191D0 (en) * | 1984-10-17 | 1984-11-21 | Glaxo Holdings Ltd | Chemical compounds |
| GB8603475D0 (en) * | 1986-02-12 | 1986-03-19 | Glaxo Group Ltd | Chemical compounds |
| GB8703007D0 (en) * | 1987-02-10 | 1987-03-18 | Glaxo Group Ltd | Chemical compounds |
| JPS63290852A (ja) * | 1987-02-10 | 1988-11-28 | グラクソ、グループ、リミテッド | 化合物 |
| US4906645A (en) * | 1988-09-12 | 1990-03-06 | Merck & Co., Inc. | Pyridyl aminoethanol compounds with growth promotion and an increase in feed efficiency |
| DE4028398A1 (de) * | 1990-09-07 | 1992-03-12 | Thomae Gmbh Dr K | Phenylethanolamine, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| AU666133B2 (en) * | 1991-10-04 | 1996-02-01 | Taisho Pharmaceutical Co., Ltd. | Alkoxyphenylalkylamine derivative |
| US8349898B2 (en) * | 2008-11-18 | 2013-01-08 | Wisconsin Alumni Research Foundation | Sigma-1 receptor ligands and methods of use |
| GB201208775D0 (en) * | 2012-05-18 | 2012-07-04 | Uni I Oslo | Chemical compounds |
| US10668030B2 (en) * | 2016-04-21 | 2020-06-02 | University Of Kentucky Research Foundation | Vesicular monoamine transporter-2 ligands and their use in the treatment of psychostimulant abuse |
| WO2023235153A1 (en) * | 2022-05-31 | 2023-12-07 | Corteva Agriscience Llc | Crystalline forms of picolinamide fungicide compound |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1618007A1 (de) * | 1967-05-09 | 1970-10-29 | Thomae Gmbh Dr K | Verfahren zur Herstellung von neuen Amino-monohalogenphenylaethanolaminen |
| DE2351281C3 (de) * | 1973-10-12 | 1981-07-30 | Dr. Karl Thomae Gmbh, 7950 Biberach | Aminophenyl-äthanolamin-Derivate, deren Herstellung und Verwendung |
| NL176168C (nl) * | 1972-12-18 | 1985-03-01 | Thomae Gmbh Dr K | Werkwijze ter bereiding respectievelijk vervaardiging van een farmaceutisch preparaat en werkwijze ter bereiding van daarbij bruikbare nieuwe gesubstitueerde 1-(4-aminofenyl)-2-amino-ethanol-derivaten die, behalve een analgetische, uterusspasmolytische en anti-spastische werking op de dwarsgestreepte spieren, in het bijzonder een beta2-mimetische en/of beta1-blokkerende werking bezitten. |
| JPS51125232A (en) * | 1975-02-05 | 1976-11-01 | Yamanouchi Pharmaceut Co Ltd | Process for preparing 4-substituted amido-3,5-dihalogeno-alpha-substituted aminomethylbenzyl alcohols |
| GB1523974A (en) * | 1975-02-05 | 1978-09-06 | Yamanouchi Pharma Co Ltd | 4-substituted amino- -aminomethylbenzyl alcohol derivatives |
| EP0006961A1 (en) * | 1978-02-21 | 1980-01-23 | Sandoz Ag | New phenylethylamines, process for their preparation, and pharmaceutical compositions containing them |
| DK268579A (da) * | 1978-07-03 | 1980-01-04 | Lilly Co Eli | Fremgangsmaade til fremstilling af phenetamolaminer |
-
1981
- 1981-11-16 NL NL8105170A patent/NL8105170A/nl not_active Application Discontinuation
- 1981-11-25 DE DE19813146623 patent/DE3146623A1/de not_active Withdrawn
- 1981-11-27 SU SU813358171A patent/SU1172449A3/ru active
- 1981-11-30 AT AT0512981A patent/AT379378B/de not_active IP Right Cessation
- 1981-12-02 ES ES507635A patent/ES8301890A1/es not_active Expired
- 1981-12-07 IT IT49853/81A patent/IT1172129B/it active
- 1981-12-07 GR GR66712A patent/GR77323B/el unknown
- 1981-12-07 DD DD81235491A patent/DD202867A5/de unknown
- 1981-12-07 CH CH7800/81A patent/CH651541A5/de not_active IP Right Cessation
- 1981-12-08 DK DK541981A patent/DK541981A/da not_active Application Discontinuation
- 1981-12-08 FI FI813934A patent/FI813934L/fi not_active Application Discontinuation
- 1981-12-09 NO NO814194A patent/NO152649C/no unknown
- 1981-12-09 BE BE0/206788A patent/BE891416A/fr not_active IP Right Cessation
- 1981-12-09 IL IL64498A patent/IL64498A/xx unknown
- 1981-12-09 CA CA000391831A patent/CA1202636A/en not_active Expired
- 1981-12-09 SE SE8107387A patent/SE8107387L/xx not_active Application Discontinuation
- 1981-12-09 JP JP56198337A patent/JPS57122048A/ja active Pending
- 1981-12-09 NZ NZ199215A patent/NZ199215A/en unknown
- 1981-12-09 GB GB8137051A patent/GB2088873B/en not_active Expired
- 1981-12-09 PL PL1981234155A patent/PL129385B1/pl unknown
- 1981-12-09 IE IE2888/81A patent/IE52007B1/en unknown
- 1981-12-09 AU AU78414/81A patent/AU547655B2/en not_active Ceased
- 1981-12-09 HU HU813708A patent/HU185676B/hu unknown
- 1981-12-09 ZA ZA818529A patent/ZA818529B/xx unknown
- 1981-12-10 FR FR8123106A patent/FR2498596B1/fr not_active Expired
- 1981-12-10 AR AR287754A patent/AR227802A1/es active
- 1981-12-10 KR KR1019810004912A patent/KR870000183B1/ko active IP Right Grant
- 1981-12-10 LU LU83830A patent/LU83830A1/de unknown
- 1981-12-10 YU YU02903/81A patent/YU290381A/xx unknown
- 1981-12-10 CS CS819178A patent/CS229924B2/cs unknown
- 1981-12-10 PH PH26726A patent/PH21599A/en unknown
- 1981-12-10 PT PT74112A patent/PT74112B/pt unknown
-
1982
- 1982-06-08 ES ES512915A patent/ES512915A0/es active Granted
- 1982-06-08 ES ES512914A patent/ES8304537A1/es not_active Expired
- 1982-06-08 ES ES512913A patent/ES512913A0/es active Granted
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A85 | Still pending on 85-01-01 | ||
| BV | The patent application has lapsed |