FI116623B - Menetelmä uusien terapeuttisesti käyttökelpoisten fenyyli-indoliyhdisteiden valmistamiseksi - Google Patents
Menetelmä uusien terapeuttisesti käyttökelpoisten fenyyli-indoliyhdisteiden valmistamiseksi Download PDFInfo
- Publication number
- FI116623B FI116623B FI961844A FI961844A FI116623B FI 116623 B FI116623 B FI 116623B FI 961844 A FI961844 A FI 961844A FI 961844 A FI961844 A FI 961844A FI 116623 B FI116623 B FI 116623B
- Authority
- FI
- Finland
- Prior art keywords
- ethyl
- chloro
- fluorophenyl
- indol
- piperidin
- Prior art date
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- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 43
- 238000002360 preparation method Methods 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 74
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 25
- -1 oxo compound Chemical class 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- PZCFPIOIAWXVIO-UHFFFAOYSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-5,5-dimethylimidazolidin-2-one Chemical compound CC1(C)CNC(=O)N1CCN1CCC(C=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 PZCFPIOIAWXVIO-UHFFFAOYSA-N 0.000 claims description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- VKCYHJWLYTUGCC-UHFFFAOYSA-N nonan-2-one Chemical compound CCCCCCCC(C)=O VKCYHJWLYTUGCC-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 4
- LBWVARIQNSNHHF-UHFFFAOYSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-1,3-diazaspiro[4.4]nonan-2-one Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C4(CCCC4)CNC3=O)CC2)=C1 LBWVARIQNSNHHF-UHFFFAOYSA-N 0.000 claims description 3
- GZKLJWGUPQBVJQ-XUWBISKJSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-5,5-dideuterioimidazolidin-2-one Chemical compound [2H]C1([2H])CNC(=O)N1CCN1CCC(C=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 GZKLJWGUPQBVJQ-XUWBISKJSA-N 0.000 claims description 3
- 239000005977 Ethylene Substances 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 150000003672 ureas Chemical class 0.000 claims description 3
- GZKLJWGUPQBVJQ-ZXSHKXLLSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-4,4,5,5-tetradeuterioimidazolidin-2-one Chemical compound [2H]C1([2H])C([2H])([2H])NC(=O)N1CCN1CCC(C=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 GZKLJWGUPQBVJQ-ZXSHKXLLSA-N 0.000 claims description 2
- GZKLJWGUPQBVJQ-KNXIQCGSSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-4,4-dideuterioimidazolidin-2-one Chemical compound O=C1NC([2H])([2H])CN1CCN1CCC(C=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 GZKLJWGUPQBVJQ-KNXIQCGSSA-N 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 241000251730 Chondrichthyes Species 0.000 claims description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 2
- 230000001588 bifunctional effect Effects 0.000 claims description 2
- 229910052805 deuterium Inorganic materials 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 125000003003 spiro group Chemical group 0.000 claims description 2
- 241000282461 Canis lupus Species 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- QHYYMSNCBYDHDH-UHFFFAOYSA-N 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]-5,5-dimethylimidazolidine-2,4-dione Chemical compound O=C1NC(=O)C(C)(C)N1CCN1CCC(C=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 QHYYMSNCBYDHDH-UHFFFAOYSA-N 0.000 claims 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 210000005056 cell body Anatomy 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 238000009432 framing Methods 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 claims 1
- GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 abstract description 14
- 229960000652 sertindole Drugs 0.000 abstract description 13
- 239000003693 atypical antipsychotic agent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- 239000000203 mixture Substances 0.000 description 61
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 230000002829 reductive effect Effects 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
- 239000003921 oil Substances 0.000 description 32
- 239000002904 solvent Substances 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
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- 230000015572 biosynthetic process Effects 0.000 description 14
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- 229910002027 silica gel Inorganic materials 0.000 description 13
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
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- 235000019341 magnesium sulphate Nutrition 0.000 description 12
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 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
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- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 238000005462 in vivo assay Methods 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
- 230000000670 limiting effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- MRZNYTMWNPAOMW-UHFFFAOYSA-N n'-(2-phenylmethoxyethyl)oxamide Chemical compound NC(=O)C(=O)NCCOCC1=CC=CC=C1 MRZNYTMWNPAOMW-UHFFFAOYSA-N 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 1
- XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-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
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QEHKBHWEUPXBCW-UHFFFAOYSA-N nitrogen trichloride Chemical compound ClN(Cl)Cl QEHKBHWEUPXBCW-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 150000002912 oxalic acid derivatives Chemical class 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 229940096717 pamine Drugs 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine acetate Natural products C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- JZWFDVDETGFGFC-UHFFFAOYSA-N salacetamide Chemical group CC(=O)NC(=O)C1=CC=CC=C1O JZWFDVDETGFGFC-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- CXYRUNPLKGGUJF-RAFJPFSSSA-M scopolamine methobromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 CXYRUNPLKGGUJF-RAFJPFSSSA-M 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
- 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 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
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Sewing Machines And Sewing (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Polyurethanes Or Polyureas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK123493 | 1993-11-01 | ||
| DK931234A DK123493D0 (da) | 1993-11-01 | 1993-11-01 | Compounds |
| DK9400407 | 1994-10-28 | ||
| PCT/DK1994/000407 WO1995012591A1 (en) | 1993-11-01 | 1994-10-28 | Phenylindole compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI961844L FI961844L (fi) | 1996-04-30 |
| FI961844A0 FI961844A0 (fi) | 1996-04-30 |
| FI116623B true FI116623B (fi) | 2006-01-13 |
Family
ID=8102507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI961844A FI116623B (fi) | 1993-11-01 | 1996-04-30 | Menetelmä uusien terapeuttisesti käyttökelpoisten fenyyli-indoliyhdisteiden valmistamiseksi |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US5703087A (cs) |
| EP (1) | EP0726898B1 (cs) |
| JP (1) | JP3898219B2 (cs) |
| KR (1) | KR100350550B1 (cs) |
| CN (1) | CN1134149A (cs) |
| AT (1) | ATE198199T1 (cs) |
| AU (1) | AU683700B2 (cs) |
| CA (1) | CA2175498C (cs) |
| CZ (1) | CZ291403B6 (cs) |
| DE (1) | DE69426462T2 (cs) |
| DK (2) | DK123493D0 (cs) |
| ES (1) | ES2154303T3 (cs) |
| FI (1) | FI116623B (cs) |
| GR (1) | GR3035462T3 (cs) |
| HU (1) | HUT76063A (cs) |
| IL (2) | IL111395A (cs) |
| LV (1) | LV12805B (cs) |
| NO (1) | NO309038B1 (cs) |
| NZ (1) | NZ275086A (cs) |
| PL (1) | PL176391B1 (cs) |
| PT (1) | PT726898E (cs) |
| RU (1) | RU2156249C2 (cs) |
| SI (1) | SI0726898T1 (cs) |
| SK (1) | SK281761B6 (cs) |
| WO (1) | WO1995012591A1 (cs) |
| ZA (1) | ZA948589B (cs) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6489341B1 (en) * | 1999-06-02 | 2002-12-03 | Sepracor Inc. | Methods for the treatment of neuroleptic and related disorders using sertindole derivatives |
| WO2001021614A1 (en) * | 1999-09-09 | 2001-03-29 | H. Lundbeck A/S | 5-aminoalkyl and 5-aminocarbonyl substituted indoles |
| US20070212412A1 (en) * | 2005-09-08 | 2007-09-13 | H. Lundbeck A/S | Stable solid formulation of sertindole |
| TW200821296A (en) * | 2006-06-01 | 2008-05-16 | Lundbeck & Co As H | Use of sertindole for the preventive treatment of suicidal behaviour |
| JP5788404B2 (ja) * | 2009-12-11 | 2015-09-30 | アウトイフオンイ トヘラペウトイクス リミテッド | イミダゾリジンジオン誘導体 |
| WO2011159760A1 (en) * | 2010-06-16 | 2011-12-22 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| PL2649066T3 (pl) | 2010-12-06 | 2017-04-28 | Autifony Therapeutics Limited | Pochodne hydantoiny przydatne jako inhibitory KV3 |
| US9193704B2 (en) | 2011-06-07 | 2015-11-24 | Autifony Therapeutics Limited | Hydantoin derivatives as KV3 inhibitors |
| CN103974944B (zh) * | 2011-12-06 | 2016-11-02 | 奥蒂福尼疗法有限公司 | 用作kv3抑制剂的乙内酰脲衍生物 |
| US9422252B2 (en) | 2012-05-22 | 2016-08-23 | Autifony Therapeutics Limited | Triazoles as Kv3 inhibitors |
| JP2015517563A (ja) | 2012-05-22 | 2015-06-22 | アウトイフオンイ トヘラペウトイクス リミテッド | Ｋｖ３阻害剤としてのヒダントイン誘導体 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE58370B1 (en) * | 1985-04-10 | 1993-09-08 | Lundbeck & Co As H | Indole derivatives |
| GB8908085D0 (en) * | 1989-04-11 | 1989-05-24 | Lundbeck & Co As H | New therapeutic use |
| DK152090D0 (da) * | 1990-06-22 | 1990-06-22 | Lundbaek A S H | Piperidylsubstituerede indolderivater |
-
1993
- 1993-11-01 DK DK931234A patent/DK123493D0/da not_active Application Discontinuation
-
1994
- 1994-10-25 IL IL11139594A patent/IL111395A/xx not_active IP Right Cessation
- 1994-10-25 IL IL11139494A patent/IL111394A/en not_active IP Right Cessation
- 1994-10-28 PL PL94314181A patent/PL176391B1/pl not_active IP Right Cessation
- 1994-10-28 CA CA002175498A patent/CA2175498C/en not_active Expired - Fee Related
- 1994-10-28 EP EP94931520A patent/EP0726898B1/en not_active Expired - Lifetime
- 1994-10-28 HU HU9601144A patent/HUT76063A/hu not_active Application Discontinuation
- 1994-10-28 AU AU80577/94A patent/AU683700B2/en not_active Ceased
- 1994-10-28 RU RU96110902/04A patent/RU2156249C2/ru not_active IP Right Cessation
- 1994-10-28 NZ NZ275086A patent/NZ275086A/en not_active IP Right Cessation
- 1994-10-28 PT PT94931520T patent/PT726898E/pt unknown
- 1994-10-28 DE DE69426462T patent/DE69426462T2/de not_active Expired - Fee Related
- 1994-10-28 DK DK94931520T patent/DK0726898T3/da active
- 1994-10-28 JP JP51296895A patent/JP3898219B2/ja not_active Expired - Fee Related
- 1994-10-28 ES ES94931520T patent/ES2154303T3/es not_active Expired - Lifetime
- 1994-10-28 US US08/635,905 patent/US5703087A/en not_active Expired - Fee Related
- 1994-10-28 CN CN94193987A patent/CN1134149A/zh active Pending
- 1994-10-28 AT AT94931520T patent/ATE198199T1/de not_active IP Right Cessation
- 1994-10-28 KR KR1019960702237A patent/KR100350550B1/ko not_active Expired - Fee Related
- 1994-10-28 CZ CZ19961248A patent/CZ291403B6/cs not_active IP Right Cessation
- 1994-10-28 SI SI9430356T patent/SI0726898T1/xx unknown
- 1994-10-28 SK SK534-96A patent/SK281761B6/sk not_active IP Right Cessation
- 1994-10-28 WO PCT/DK1994/000407 patent/WO1995012591A1/en active IP Right Grant
- 1994-11-01 ZA ZA948589A patent/ZA948589B/xx unknown
-
1996
- 1996-04-30 NO NO961746A patent/NO309038B1/no not_active IP Right Cessation
- 1996-04-30 FI FI961844A patent/FI116623B/fi active IP Right Grant
-
2001
- 2001-02-22 GR GR20010400296T patent/GR3035462T3/el not_active IP Right Cessation
- 2001-12-20 LV LV010178A patent/LV12805B/xx unknown
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