PT100620B - Derivados de tetra-hidrocarbazol, seu uso e preparacao e composicoes farmaceuticas que os contem - Google Patents
Derivados de tetra-hidrocarbazol, seu uso e preparacao e composicoes farmaceuticas que os contem Download PDFInfo
- Publication number
- PT100620B PT100620B PT100620A PT10062092A PT100620B PT 100620 B PT100620 B PT 100620B PT 100620 A PT100620 A PT 100620A PT 10062092 A PT10062092 A PT 10062092A PT 100620 B PT100620 B PT 100620B
- Authority
- PT
- Portugal
- Prior art keywords
- tetrahydrocarbazole
- amino
- compound
- formula
- carboxamido
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 238000000034 method Methods 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 230000008569 process Effects 0.000 claims abstract description 32
- -1 nitro, hydroxy Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 18
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 12
- 206010027599 migraine Diseases 0.000 claims abstract description 12
- 239000000556 agonist Substances 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 34
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 20
- 238000010511 deprotection reaction Methods 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- PMQBOSGFSARWCB-MRVPVSSYSA-N (6R)-6-amino-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide Chemical compound N1C2=CC=C(C(N)=O)C=C2C2=C1CC[C@@H](N)C2 PMQBOSGFSARWCB-MRVPVSSYSA-N 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- JSUDTVCLELZPML-UHFFFAOYSA-N 2-(6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)acetonitrile Chemical compound N1C2=CC=C(CC#N)C=C2C2=C1CCC(N)C2 JSUDTVCLELZPML-UHFFFAOYSA-N 0.000 claims description 2
- DDLAOJUFZYVVOR-UHFFFAOYSA-N 6-amino-6,7,8,9-tetrahydro-5h-carbazole-3-carbonitrile Chemical compound N1C2=CC=C(C#N)C=C2C2=C1CCC(N)C2 DDLAOJUFZYVVOR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 2
- 238000005576 amination reaction Methods 0.000 claims description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 2
- XXMSXOXISYFBRN-UHFFFAOYSA-N ethyl 6-amino-6,7,8,9-tetrahydro-5h-carbazole-3-carboxylate Chemical compound C1CC(N)CC2=C1NC1=CC=C(C(=O)OCC)C=C12 XXMSXOXISYFBRN-UHFFFAOYSA-N 0.000 claims description 2
- AQOVPROETIEWSI-UHFFFAOYSA-N (6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)-piperidin-1-ylmethanone Chemical compound C1=C2C=3CC(N)CCC=3NC2=CC=C1C(=O)N1CCCCC1 AQOVPROETIEWSI-UHFFFAOYSA-N 0.000 claims 1
- ISPGVNMLUNMFJN-UHFFFAOYSA-N (6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)-pyrrolidin-1-ylmethanone Chemical compound C1=C2C=3CC(N)CCC=3NC2=CC=C1C(=O)N1CCCC1 ISPGVNMLUNMFJN-UHFFFAOYSA-N 0.000 claims 1
- RPRUKHVTDCBCDS-UHFFFAOYSA-N 6-(trifluoromethyl)-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound N1C2=CC=C(C(F)(F)F)C=C2C2=C1CCC(N)C2 RPRUKHVTDCBCDS-UHFFFAOYSA-N 0.000 claims 1
- LJCBTRREHXRQCD-UHFFFAOYSA-N 6-bromo-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound N1C2=CC=C(Br)C=C2C2=C1CCC(N)C2 LJCBTRREHXRQCD-UHFFFAOYSA-N 0.000 claims 1
- KOQIMIGXLYBKHL-UHFFFAOYSA-N 6-butoxy-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound C1CC(N)CC2=C1NC1=CC=C(OCCCC)C=C12 KOQIMIGXLYBKHL-UHFFFAOYSA-N 0.000 claims 1
- BODQGEOXSNZRGK-UHFFFAOYSA-N 6-chloro-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound N1C2=CC=C(Cl)C=C2C2=C1CCC(N)C2 BODQGEOXSNZRGK-UHFFFAOYSA-N 0.000 claims 1
- ZQOUZQXHFNHWPT-UHFFFAOYSA-N 6-methoxy-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound C1CC(N)CC2=C1NC1=CC=C(OC)C=C12 ZQOUZQXHFNHWPT-UHFFFAOYSA-N 0.000 claims 1
- NWTOHMWTBNGTEF-UHFFFAOYSA-N 6-methyl-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound C1CC(N)CC2=C1NC1=CC=C(C)C=C12 NWTOHMWTBNGTEF-UHFFFAOYSA-N 0.000 claims 1
- IWBWMPCHOBTEEO-UHFFFAOYSA-N 6-nitro-2,3,4,9-tetrahydro-1h-carbazol-3-amine Chemical compound N1C2=CC=C([N+]([O-])=O)C=C2C2=C1CCC(N)C2 IWBWMPCHOBTEEO-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- VFCUMCQFIQCWBQ-UHFFFAOYSA-N n-(6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)acetamide Chemical compound C1CC(N)CC2=C1NC1=CC=C(NC(=O)C)C=C12 VFCUMCQFIQCWBQ-UHFFFAOYSA-N 0.000 claims 1
- GJMSWPBXIRUNNQ-UHFFFAOYSA-N n-(6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)methanesulfonamide Chemical compound C1CC(N)CC2=C1NC1=CC=C(NS(=O)(=O)C)C=C12 GJMSWPBXIRUNNQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 56
- 239000000047 product Substances 0.000 description 46
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 239000007787 solid Substances 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000012458 free base Substances 0.000 description 17
- PWUJQPNLEZZILN-UHFFFAOYSA-N 2-(4-oxocyclohexyl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)CC1 PWUJQPNLEZZILN-UHFFFAOYSA-N 0.000 description 16
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- 238000003756 stirring Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
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- 238000001816 cooling Methods 0.000 description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 description 7
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
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- 239000004031 partial agonist Substances 0.000 description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
- OWIOWWPDSOTTNG-UHFFFAOYSA-N 6-amino-6,7,8,9-tetrahydro-5h-carbazole-3-carboxamide;hydrochloride Chemical compound Cl.N1C2=CC=C(C(N)=O)C=C2C2=C1CCC(N)C2 OWIOWWPDSOTTNG-UHFFFAOYSA-N 0.000 description 5
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- 239000011734 sodium Substances 0.000 description 5
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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- 239000010410 layer Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 3
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- DDOLWFKTHFCPNA-UHFFFAOYSA-N 2-(6-amino-6,7,8,9-tetrahydro-5h-carbazol-3-yl)acetonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.N1C2=CC=C(CC#N)C=C2C2=C1CCC(N)C2 DDOLWFKTHFCPNA-UHFFFAOYSA-N 0.000 description 2
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- 239000001119 stannous chloride Substances 0.000 description 1
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- 235000011044 succinic acid Nutrition 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
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- 239000013589 supplement Substances 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- BLEBXBOPRPACGB-UHFFFAOYSA-N tert-butyl 2-[(6-cyano-2,3,4,9-tetrahydro-1h-carbazol-3-yl)amino]acetate Chemical compound N1C2=CC=C(C#N)C=C2C2=C1CCC(NCC(=O)OC(C)(C)C)C2 BLEBXBOPRPACGB-UHFFFAOYSA-N 0.000 description 1
- HZTXOKYBDOFKIR-UHFFFAOYSA-N tert-butyl n-(6-cyano-2,3,4,9-tetrahydro-1h-carbazol-3-yl)carbamate Chemical compound N1C2=CC=C(C#N)C=C2C2=C1CCC(NC(=O)OC(C)(C)C)C2 HZTXOKYBDOFKIR-UHFFFAOYSA-N 0.000 description 1
- GUQWIDZADFDWOI-UHFFFAOYSA-N tert-butyl n-[6-(cyanomethyl)-2,3,4,9-tetrahydro-1h-carbazol-3-yl]carbamate Chemical compound N1C2=CC=C(CC#N)C=C2C2=C1CCC(NC(=O)OC(C)(C)C)C2 GUQWIDZADFDWOI-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
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Classifications
-
- 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
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919113802A GB9113802D0 (en) | 1991-06-26 | 1991-06-26 | Medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT100620A PT100620A (pt) | 1993-09-30 |
| PT100620B true PT100620B (pt) | 1999-01-29 |
Family
ID=10697363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT100620A PT100620B (pt) | 1991-06-26 | 1992-06-24 | Derivados de tetra-hidrocarbazol, seu uso e preparacao e composicoes farmaceuticas que os contem |
Country Status (34)
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9211277D0 (en) | 1992-05-28 | 1992-07-15 | Glaxo Group Inc | Pharmaceutical compositions |
| GB9226566D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
| US5616603A (en) * | 1995-05-26 | 1997-04-01 | Smithkline Beecham Plc | Enantiomers of carbazole derivatives as 5-HT1 -like agonists |
| GB9226530D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
| US5618948A (en) * | 1995-05-26 | 1997-04-08 | Smithkline Beecham P.L.C. | Process for preparing an enantiomer of a carbazole derivative |
| EP0749962B1 (en) * | 1995-06-23 | 2000-11-02 | Eli Lilly And Company | 6-substituted-1,2,3,4-tetrahydro-9H-carbazoles and 7-substituted-10H-cyclohepta(7,6-B)indoles |
| US5917054A (en) * | 1995-07-18 | 1999-06-29 | Smithkline Beecham P.L.C. | Process for preparing enantiomers of carbazole derivatives as 5-HT1 -like agonists |
| US5708187A (en) * | 1996-06-27 | 1998-01-13 | Eli Lilly And Company | 6-substituted-1,2,3,4-tetrahydro-9H-carbazoles and 7-substituted-10H-cyclohepta 7,6-B!indoles: New 5-HT1F agonists |
| US5891885A (en) * | 1996-10-09 | 1999-04-06 | Algos Pharmaceutical Corporation | Method for treating migraine |
| GB9723061D0 (en) * | 1997-10-31 | 1998-01-07 | Vanguard Medica Ltd | Medicaments |
| US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
| US6066092A (en) * | 1997-11-06 | 2000-05-23 | Cady; Roger K. | Preemptive prophylaxis of migraine device and method |
| GB9808069D0 (en) * | 1998-04-16 | 1998-06-17 | Vanguard Medica Ltd | Novel processes |
| GB9817911D0 (en) * | 1998-08-17 | 1998-10-14 | Vanguard Medica Ltd | New use |
| US20030198669A1 (en) * | 2001-07-05 | 2003-10-23 | R.T. Alamo Ventures I, Llc | Compositions and methods for rapid dissolving formulations of dihydroergotamine and caffeine for the treatment of migraine |
| US20030017175A1 (en) * | 2001-07-05 | 2003-01-23 | R.T. Alamo Ventures I, Inc. | Sublingual administration of dihydroergotamine for the treatment of migraine |
| US6685951B2 (en) | 2001-07-05 | 2004-02-03 | R. T. Alamo Ventures I, Inc. | Administration of dihydroergotamine as a sublingual spray or aerosol for the treatment of migraine |
| AU2002338726B2 (en) * | 2001-09-28 | 2007-03-15 | F. Hoffmann-La Roche Ag | Pseudopolymorphic forms of carvedilol |
| RU2340619C2 (ru) | 2002-06-21 | 2008-12-10 | Сувен Лайф Сайенсиз Лимитед | Новые тетрациклические арилсульфонилиндолы с аффинностью к серотониновым рецепторам, пригодные в качестве лекарственных средств, способ их получения и содержащие их фармацевтические композиции |
| ES2336664T3 (es) | 2002-06-21 | 2010-04-15 | Suven Life Sciences Limited | Arilaquil indoles que tienen afinidad por receptores de serotonina utiles como agentes terapeuticos, procesos para su preparacion y composiciones farmaceuticas que los contienen. |
| AU2003237599B2 (en) | 2002-11-28 | 2009-06-18 | Suven Life Sciences Limited | N-arylsulfonyl-3-substituted indoles having serotonin receptor affinity, process for their preparation and pharmaceutical composition containing them |
| PT1567492E (pt) | 2002-11-28 | 2013-07-22 | Suven Life Sciences Ltd | N-arilsulfonil-3-aminoalcoxi-indóis |
| KR100739987B1 (ko) | 2002-12-18 | 2007-07-16 | 수벤 라이프 사이언시스 리미티드 | 세로토닌 수용체 친화력을 가지는 테트라사이클릭 3-치환인돌 |
| RU2430088C2 (ru) * | 2004-07-14 | 2011-09-27 | Центарис Гмбх | Производные тетрагидрокарбазола и фармацевтическая композиция на их основе |
| US7601856B2 (en) | 2006-07-27 | 2009-10-13 | Wyeth | Benzofurans as potassium ion channel modulators |
| JP5220013B2 (ja) * | 2006-08-07 | 2013-06-26 | アクテリオン ファーマシューティカルズ リミテッド | （３−アミノ−１，２，３，４−テトラヒドロ−９ｈ−カルバゾール−９−イル）−酢酸誘導体 |
| JP2010522135A (ja) | 2006-10-09 | 2010-07-01 | チャールストン ラボラトリーズ，インコーポレイテッド | 医薬組成物 |
| ES2691033T3 (es) | 2007-02-11 | 2018-11-23 | Map Pharmaceuticals Inc. | Método de administración terapéutica de DHE para activar el alivio rápido de la migraña a la vez que se reduce al mínimo el perfil de los efectos secundarios |
| US20090069399A1 (en) * | 2007-09-12 | 2009-03-12 | Protia, Llc | Deuterium-enriched frovatriptan |
| CA2905541C (en) | 2008-01-09 | 2020-02-11 | Charleston Laboratories, Inc. | Pharmaceutical compositions comprising an antiemetic and an opioid analgesic |
| WO2010073253A1 (en) * | 2008-12-22 | 2010-07-01 | Natco Pharma Limited | Method for preparing an optically active frovatriptan |
| CA2767576C (en) | 2009-07-08 | 2020-03-10 | Charleston Laboratories Inc. | Pharmaceutical compositions comprising an antiemetic and an opioid analgesic |
| WO2011050140A1 (en) | 2009-10-22 | 2011-04-28 | Blue Fury Consulting, L.L.C. | Posterior cervical fusion system and techniques |
| US10098674B2 (en) | 2009-10-22 | 2018-10-16 | Nuvasive, Inc. | System and method for posterior cervical fusion |
| EP2734634B1 (en) | 2011-07-22 | 2019-08-21 | The University of Chicago | Igf-1 for use in the treatment of migraine |
| CA2895816C (en) | 2012-12-21 | 2021-02-23 | Map Pharmaceuticals, Inc. | 8'-hydroxy-dihydroergotamine compounds and compositions |
| EP2816030A1 (en) | 2013-06-20 | 2014-12-24 | Duke Chem, S. A. | Process for the preparation of frovatriptan and its enantiomer |
| GB201312768D0 (en) * | 2013-07-17 | 2013-08-28 | Ge Healthcare Ltd | Work-up procedure |
| US10179109B2 (en) | 2016-03-04 | 2019-01-15 | Charleston Laboratories, Inc. | Pharmaceutical compositions comprising 5HT receptor agonist and antiemetic particulates |
| EP3766483A1 (en) | 2019-07-19 | 2021-01-20 | BioPharma Synergies, S. L. | Orodispersible powder composition comprising a triptan |
| WO2025038666A2 (en) * | 2023-08-13 | 2025-02-20 | GATC Health Corp | Compounds and methods for treating addiction |
| CN119499195A (zh) * | 2024-11-26 | 2025-02-25 | 青岛国信制药有限公司 | 一种快速吸收琥珀酸呋罗曲坦片及其制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3642816A (en) * | 1967-08-10 | 1972-02-15 | Sterling Drug Inc | 3-acetamido-1 2 3 4-tetrahydrocarbazole |
| US3959309A (en) * | 1968-01-24 | 1976-05-25 | Sterling Drug Inc. | 3-Amido-1,2,3,4-tetrahydrocarbazoles |
| US4062864A (en) * | 1968-01-24 | 1977-12-13 | Sterling Drug Inc. | 3-Hydroxy carbazole derivatives |
| US3592824A (en) * | 1970-03-12 | 1971-07-13 | Miles Lab | 3-substituted amino-1,2,3,4-tetrahydrocarbazoles |
| BE787537A (fr) * | 1971-08-16 | 1973-02-14 | Sterling Drug Inc | Tetrahydrocarbazoles |
| US4172834A (en) | 1971-08-16 | 1979-10-30 | Sterling Drug Inc. | 3-Amino-tetrahydrocarbazoles |
| DE2815926A1 (de) * | 1978-04-13 | 1979-10-18 | Boehringer Mannheim Gmbh | Neue carbazolyl-(4)-oxy-propanolamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US4257952A (en) * | 1977-06-06 | 1981-03-24 | Sterling Drug Inc. | 3-Amino-tetrahydrocarbazoles |
| US4254134A (en) * | 1978-03-17 | 1981-03-03 | Endo Laboratories, Inc. | Antidepressant 2-amino- and -2-(substituted amino)-cis-hexahydro-carbazoles |
| EP0115607A1 (de) * | 1983-01-04 | 1984-08-15 | MERCK PATENT GmbH | Tetrahydrocarbazolderivate |
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