NO311515B1 - Tetrahydrobenzindolforbindelser, og farmasöytiske preparater inneholdende slike forbindelser - Google Patents
Tetrahydrobenzindolforbindelser, og farmasöytiske preparater inneholdende slike forbindelser Download PDFInfo
- Publication number
- NO311515B1 NO311515B1 NO19986141A NO986141A NO311515B1 NO 311515 B1 NO311515 B1 NO 311515B1 NO 19986141 A NO19986141 A NO 19986141A NO 986141 A NO986141 A NO 986141A NO 311515 B1 NO311515 B1 NO 311515B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- compound
- mmol
- tetrahydrobenz
- mass spectrum
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 250
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 14
- GHDKZRYOSSRTLA-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-benzo[g]indole Chemical class C1C=C2C=CC=CC2=C2C1CCN2 GHDKZRYOSSRTLA-UHFFFAOYSA-N 0.000 title 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- 125000002252 acyl group Chemical group 0.000 claims abstract description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 9
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 5
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 4
- -1 methanesulfonyloxy, ethanesulfonyloxy Chemical group 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 22
- 150000002148 esters Chemical group 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 10
- 108091005436 5-HT7 receptors Proteins 0.000 abstract description 7
- 229940076279 serotonin Drugs 0.000 abstract description 4
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 210000004748 cultured cell Anatomy 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 description 279
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 113
- 238000001819 mass spectrum Methods 0.000 description 95
- 238000006243 chemical reaction Methods 0.000 description 80
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 77
- 230000002829 reductive effect Effects 0.000 description 66
- 239000002904 solvent Substances 0.000 description 65
- 238000005160 1H NMR spectroscopy Methods 0.000 description 62
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 29
- 238000010898 silica gel chromatography Methods 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 239000007795 chemical reaction product Substances 0.000 description 25
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 24
- 238000001704 evaporation Methods 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 230000008020 evaporation Effects 0.000 description 17
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 14
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 101150041968 CDC13 gene Proteins 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 235000011181 potassium carbonates Nutrition 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 239000012312 sodium hydride Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 201000000980 schizophrenia Diseases 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- OMPXTQYWYRWWPH-UHFFFAOYSA-N 4-phenyl-1,2,3,6-tetrahydropyridine Chemical class C1NCCC(C=2C=CC=CC=2)=C1 OMPXTQYWYRWWPH-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- LHRYYSNFHJCZDT-UHFFFAOYSA-N 4-(4-methylphenyl)-1,2,3,6-tetrahydropyridine Chemical compound C1=CC(C)=CC=C1C1=CCNCC1 LHRYYSNFHJCZDT-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 208000019901 Anxiety disease Diseases 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 230000036506 anxiety Effects 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- CRJMOQUKRGIGLY-UHFFFAOYSA-N 2a,3,4,5-tetrahydro-1h-benzo[cd]indol-2-one Chemical compound C1CCC2C(=O)NC3=CC=CC1=C32 CRJMOQUKRGIGLY-UHFFFAOYSA-N 0.000 description 5
- LZAYOZUFUAMFLD-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-hydroxypiperidine Chemical compound C=1C=C(Cl)C=CC=1C1(O)CCNCC1 LZAYOZUFUAMFLD-UHFFFAOYSA-N 0.000 description 5
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical class C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 5
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- XVCXKZISCOBPDZ-UHFFFAOYSA-N 2a-(4-bromobutyl)-1,3,4,5-tetrahydrobenzo[cd]indol-2-one Chemical compound C1CCC2=CC=CC3=C2C1(CCCCBr)C(=O)N3 XVCXKZISCOBPDZ-UHFFFAOYSA-N 0.000 description 4
- POGWXTJNUCZEPR-UHFFFAOYSA-N 4-phenyl-1,2,3,6-tetrahydropyridin-1-ium;chloride Chemical compound Cl.C1NCCC(C=2C=CC=CC=2)=C1 POGWXTJNUCZEPR-UHFFFAOYSA-N 0.000 description 4
- 208000020925 Bipolar disease Diseases 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
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- 208000028683 bipolar I disease Diseases 0.000 description 4
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- 230000005593 dissociations Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000005658 halogenation reaction Methods 0.000 description 4
- UPZJLQCUYUTZIE-UHFFFAOYSA-N hydron;4-phenylpiperidine;chloride Chemical compound Cl.C1CNCCC1C1=CC=CC=C1 UPZJLQCUYUTZIE-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000003340 mental effect Effects 0.000 description 4
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- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- FRICBZWJFIRJOB-UHFFFAOYSA-N 2-piperazin-1-ylbenzonitrile Chemical compound N#CC1=CC=CC=C1N1CCNCC1 FRICBZWJFIRJOB-UHFFFAOYSA-N 0.000 description 3
- LJUHEEFEADORHV-UHFFFAOYSA-N 3-piperazin-1-ylbenzonitrile Chemical compound N#CC1=CC=CC(N2CCNCC2)=C1 LJUHEEFEADORHV-UHFFFAOYSA-N 0.000 description 3
- BYHRWYVRKPRAPH-UHFFFAOYSA-N 4-(2-methoxyphenyl)-1,2,3,6-tetrahydropyridine Chemical compound COC1=CC=CC=C1C1=CCNCC1 BYHRWYVRKPRAPH-UHFFFAOYSA-N 0.000 description 3
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 3
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
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- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 2
- JDVUSTNITSGJOH-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)piperazine Chemical compound CC1=CC=CC(C)=C1N1CCNCC1 JDVUSTNITSGJOH-UHFFFAOYSA-N 0.000 description 2
- YOOLKLKIUUTLFC-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-methylpiperazine Chemical compound CC1CNCCN1C1=CC=C(Cl)C=C1 YOOLKLKIUUTLFC-UHFFFAOYSA-N 0.000 description 2
- FRFKCMNQNNNZNO-UHFFFAOYSA-N 1-[3-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=CN=C1N1CCNCC1 FRFKCMNQNNNZNO-UHFFFAOYSA-N 0.000 description 2
- IAOMYUZAXMFANI-UHFFFAOYSA-N 1-[6-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=N1 IAOMYUZAXMFANI-UHFFFAOYSA-N 0.000 description 2
- GPYLCFQEKPUWLD-UHFFFAOYSA-N 1h-benzo[cd]indol-2-one Chemical compound C1=CC(C(=O)N2)=C3C2=CC=CC3=C1 GPYLCFQEKPUWLD-UHFFFAOYSA-N 0.000 description 2
- QDMCWIHRLTVLIY-UHFFFAOYSA-N 2-methyl-1-(3-methylphenyl)piperazine Chemical compound CC1CNCCN1C1=CC=CC(C)=C1 QDMCWIHRLTVLIY-UHFFFAOYSA-N 0.000 description 2
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- 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
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- 238000006386 neutralization reaction Methods 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 1
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- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000003863 physical function Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- WADXWZJPSRZZHZ-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-phenylpiperidine-1-carboxylate 4-phenylpiperidin-4-ol Chemical compound OC1(CCNCC1)C1=CC=CC=C1.OC1(CCN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1 WADXWZJPSRZZHZ-UHFFFAOYSA-N 0.000 description 1
- WWESMGYIANHHAE-UHFFFAOYSA-N tert-butyl 4-methoxy-4-phenylpiperidine-1-carboxylate Chemical compound C=1C=CC=CC=1C1(OC)CCN(C(=O)OC(C)(C)C)CC1 WWESMGYIANHHAE-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
- C07D209/92—Naphthostyrils
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16970296 | 1996-06-28 | ||
| JP9627197 | 1997-04-15 | ||
| JP13020197 | 1997-05-21 | ||
| JP14437697 | 1997-06-03 | ||
| PCT/JP1997/002226 WO1998000400A1 (fr) | 1996-06-28 | 1997-06-27 | Composes de tetrahydrobenzindole |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO986141D0 NO986141D0 (no) | 1998-12-28 |
| NO986141L NO986141L (no) | 1999-02-17 |
| NO311515B1 true NO311515B1 (no) | 2001-12-03 |
Family
ID=27468418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19986141A NO311515B1 (no) | 1996-06-28 | 1998-12-28 | Tetrahydrobenzindolforbindelser, og farmasöytiske preparater inneholdende slike forbindelser |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6355642B1 (es) |
| EP (1) | EP0937715B1 (es) |
| JP (1) | JP4076234B2 (es) |
| AT (1) | ATE296801T1 (es) |
| DE (1) | DE69733427T2 (es) |
| ES (1) | ES2243999T3 (es) |
| NO (1) | NO311515B1 (es) |
| WO (1) | WO1998000400A1 (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1129578C (zh) | 1997-12-25 | 2003-12-03 | 明治制果株式会社 | 四氢苯并吲哚衍生物 |
| CA2329319A1 (en) * | 1998-04-22 | 1999-10-28 | Meiji Seika Kaisha, Ltd. | Optically active tetrahydrobenzindole derivatives |
| US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
| GB9828004D0 (en) * | 1998-12-18 | 1999-02-10 | Smithkline Beecham Plc | Use |
| AU1025601A (en) * | 1999-10-18 | 2001-04-30 | Smithkline Beecham Plc | Tetrahydrobenzindolone derivatives, their preparation and their use as 5-ht7 receptor antagonists |
| JP2004231514A (ja) * | 2000-08-31 | 2004-08-19 | Meiji Seika Kaisha Ltd | ５−ｈｔ７受容体結合能を有し、かつ代謝的に安定なテトラヒドロベンズインドール誘導体 |
| ITRM20010356A1 (it) * | 2001-06-21 | 2002-12-23 | Sigma Tau Ind Farmaceuti | "5-alogeno derivati della triptamina utili come ligandi del recettore5-ht6 e/o 5-ht7 della serotonina. |
| US7786094B2 (en) * | 2001-10-09 | 2010-08-31 | Biopolymer Engineering, Inc. | Use of beta-glucans against biological warfare weapons and pathogens including anthrax |
| EP1676840A1 (en) | 2004-12-28 | 2006-07-05 | Laboratorios Del Dr. Esteve, S.A. | 5-HT7 Receptor antagonists |
| US7553965B2 (en) | 2002-11-07 | 2009-06-30 | Laboratories Del Dr. Esteve, S.A. | 5-HT7 receptor antagonists |
| MXPA05013365A (es) * | 2003-06-20 | 2006-04-05 | Arena Pharm Inc | Derivados de n-fenil-piperazina y metodos para profilaxis o tratamiento de enfermedades asociadas con el receptor 5ht2c. |
| KR101151653B1 (ko) | 2003-09-17 | 2012-06-28 | 얀센 파마슈티카 엔.브이. | 융합된 헤테로사이클릭 화합물 |
| NZ551543A (en) * | 2004-05-11 | 2009-12-24 | Egis Gyogyszergyar Nyrt | Pyridine derivatives of alkyl oxindoles as 5-HT7 receptor active agents |
| CA2594987A1 (en) * | 2004-12-14 | 2006-06-22 | Shionogi & Co., Ltd. | Therapeutic agent for constipation |
| WO2007007072A1 (en) * | 2005-07-07 | 2007-01-18 | Bio-Medisinsk Innovasjon As | 5-htx modulators |
| CA2616937A1 (en) | 2005-07-29 | 2007-02-08 | F. Hoffman-La Roche Ag | Indol-3-yl-carbonyl-piperidin and piperazin derivatives |
| US7598255B2 (en) | 2005-08-04 | 2009-10-06 | Janssen Pharmaceutica Nv | Pyrimidine compounds as serotonin receptor modulators |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0429341A3 (en) * | 1989-11-20 | 1991-11-13 | Rhone-Poulenc Sante | Heterocyclic derivatives, their preparation and pharmaceuticals containing them |
| FR2662696A2 (fr) | 1989-12-13 | 1991-12-06 | Rhone Poulenc Sante | Antagonistes de la serotonine, leur preparation et medicaments les contenant. |
| US5077293A (en) | 1990-06-29 | 1991-12-31 | Bristol-Myers Squibb Co. | 1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines |
| JP3190858B2 (ja) | 1997-07-23 | 2001-07-23 | 山形日本電気株式会社 | 半導体装置およびその製造方法 |
-
1997
- 1997-06-27 DE DE69733427T patent/DE69733427T2/de not_active Expired - Lifetime
- 1997-06-27 EP EP97928490A patent/EP0937715B1/en not_active Expired - Lifetime
- 1997-06-27 US US09/214,114 patent/US6355642B1/en not_active Expired - Lifetime
- 1997-06-27 JP JP50398498A patent/JP4076234B2/ja not_active Expired - Fee Related
- 1997-06-27 AT AT97928490T patent/ATE296801T1/de not_active IP Right Cessation
- 1997-06-27 ES ES97928490T patent/ES2243999T3/es not_active Expired - Lifetime
- 1997-06-27 WO PCT/JP1997/002226 patent/WO1998000400A1/ja active IP Right Grant
-
1998
- 1998-12-28 NO NO19986141A patent/NO311515B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO986141L (no) | 1999-02-17 |
| WO1998000400A1 (fr) | 1998-01-08 |
| NO986141D0 (no) | 1998-12-28 |
| EP0937715A4 (en) | 2001-01-17 |
| DE69733427D1 (de) | 2005-07-07 |
| DE69733427T2 (de) | 2006-04-27 |
| EP0937715A1 (en) | 1999-08-25 |
| US6355642B1 (en) | 2002-03-12 |
| ATE296801T1 (de) | 2005-06-15 |
| JP4076234B2 (ja) | 2008-04-16 |
| ES2243999T3 (es) | 2005-12-01 |
| EP0937715B1 (en) | 2005-06-01 |
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|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |