FI113536B - Menetelmä terapeuttisesti käyttökelpoisten 5-aryyli-indolijohdannaisten valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten 5-aryyli-indolijohdannaisten valmistamiseksi Download PDFInfo
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- FI113536B FI113536B FI943976A FI943976A FI113536B FI 113536 B FI113536 B FI 113536B FI 943976 A FI943976 A FI 943976A FI 943976 A FI943976 A FI 943976A FI 113536 B FI113536 B FI 113536B
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- alkyl
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- compound
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- 238000000034 method Methods 0.000 title claims description 19
- 230000008569 process Effects 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 4
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- 239000003054 catalyst Substances 0.000 claims description 11
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- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
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- 229910052723 transition metal Inorganic materials 0.000 claims description 5
- 150000003624 transition metals Chemical class 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 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- ANOUZLQGSGLSEL-UHFFFAOYSA-N 5-pyrimidin-5-yl-3-pyrrolidin-3-yl-1h-indole Chemical compound C1NCCC1C1=CNC2=CC=C(C=3C=NC=NC=3)C=C12 ANOUZLQGSGLSEL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
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- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 125000006178 methyl benzyl group Chemical group 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 230000002103 transcriptional effect Effects 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 18
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- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 10
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- 125000005842 heteroatom Chemical group 0.000 abstract 2
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- 230000002950 deficient Effects 0.000 abstract 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
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Classifications
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- 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
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- 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
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- 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
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- 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
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
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- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- 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
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- 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
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2208—Compounds having tin linked only to carbon, hydrogen and/or halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11528293A | 1993-08-31 | 1993-08-31 | |
| US11528293 | 1993-08-31 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI943976A0 FI943976A0 (fi) | 1994-08-30 |
| FI943976A FI943976A (fi) | 1995-03-01 |
| FI113536B true FI113536B (fi) | 2004-05-14 |
Family
ID=22360355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI943976A FI113536B (fi) | 1993-08-31 | 1994-08-30 | Menetelmä terapeuttisesti käyttökelpoisten 5-aryyli-indolijohdannaisten valmistamiseksi |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US5849739A (ja) |
| EP (1) | EP0716649B1 (ja) |
| JP (1) | JP2860603B2 (ja) |
| KR (1) | KR100191973B1 (ja) |
| CN (1) | CN1129933A (ja) |
| AT (1) | ATE170836T1 (ja) |
| AU (1) | AU686654B2 (ja) |
| BR (1) | BR9407402A (ja) |
| CA (1) | CA2169179C (ja) |
| CO (1) | CO4230238A1 (ja) |
| CZ (1) | CZ59996A3 (ja) |
| DE (1) | DE69413240T2 (ja) |
| DK (1) | DK0716649T3 (ja) |
| EC (1) | ECSP941122A (ja) |
| EG (1) | EG20547A (ja) |
| ES (1) | ES2122289T3 (ja) |
| FI (1) | FI113536B (ja) |
| HU (1) | HUT75646A (ja) |
| IL (1) | IL110773A (ja) |
| MY (1) | MY111127A (ja) |
| NO (1) | NO960818D0 (ja) |
| NZ (1) | NZ267487A (ja) |
| PE (1) | PE11895A1 (ja) |
| PL (1) | PL177604B1 (ja) |
| WO (1) | WO1995006636A1 (ja) |
| ZA (1) | ZA946608B (ja) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5559129A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc | Indole derivatives |
| US5545644A (en) * | 1990-10-15 | 1996-08-13 | Pfizer Inc. | Indole derivatives |
| US5607951A (en) * | 1990-10-15 | 1997-03-04 | Pfizer Inc | Indole derivatives |
| US5578612A (en) * | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
| US5559246A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc. | Indole derivatives |
| CZ59996A3 (en) * | 1993-08-31 | 1996-06-12 | Pfizer | 5-arylindole derivatives per se and for treating diseases, intermediates for their preparation and pharmaceutical compositions based thereon |
| GB9417310D0 (en) | 1994-08-27 | 1994-10-19 | Pfizer Ltd | Therapeutic agents |
| GB9420529D0 (en) | 1994-10-12 | 1994-11-30 | Pfizer Ltd | Indoles |
| JPH11510177A (ja) * | 1995-08-07 | 1999-09-07 | メルク シヤープ エンド ドーム リミテツド | 置換１−インドリルプロピル−４−フェネチルピペラジン誘導体 |
| EP1003738B1 (en) | 1997-08-09 | 2003-11-19 | SmithKline Beecham plc | Bicyclic compounds as ligands for 5-ht1 receptors |
| WO1999053956A1 (fr) * | 1998-04-16 | 1999-10-28 | Yamanouchi Pharmaceutical Co., Ltd. | Remedes contre l'obesite |
| US5994352A (en) * | 1998-11-13 | 1999-11-30 | Pfizer Inc. | 5-arylindole derivatives |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124931D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124936D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| DE10159922A1 (de) * | 2001-12-06 | 2003-06-26 | Gruenenthal Gmbh | Substituierte 2-Pyrrolidin-2-yl-1H-indol-Derivate |
| NZ533865A (en) | 2002-02-12 | 2006-02-24 | Smithkline Beecham Corp | Nicotinamide derivates useful as p38 inhibitors |
| US7332508B2 (en) | 2002-12-18 | 2008-02-19 | Novo Nordisk A/S | Substituted homopiperidine, piperidine or pyrrolidine derivatives |
| GB0308201D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308185D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308186D0 (en) | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0318814D0 (en) | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| WO2005066157A1 (en) * | 2004-01-02 | 2005-07-21 | Suven Life Sciences | 3-(pyrolidin-3-l) indoles as 5-ht6 receptor modulators |
| US7223994B2 (en) * | 2004-06-03 | 2007-05-29 | International Business Machines Corporation | Strained Si on multiple materials for bulk or SOI substrates |
| JP6440625B2 (ja) | 2012-11-14 | 2018-12-19 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 精神分裂病を処置するための方法および組成物 |
| US10336701B2 (en) | 2017-08-10 | 2019-07-02 | Janssen Pharmaceutica Nv | Pyridin-2-one derivatives of formula (II) useful as EP3 receptor antagonists |
| US10399944B2 (en) | 2017-08-10 | 2019-09-03 | Janssen Pharmaceutica Nv | Pyridin-2-one derivatives of formula (III) useful as EP3 receptor antagonists |
| US10590083B2 (en) | 2017-08-10 | 2020-03-17 | Janssen Pharmaceutica Nv | Pyridin-2-one derivatives of formula (I) useful as EP3 receptor antagonists |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2773875A (en) * | 1952-03-28 | 1956-12-11 | Hoffmann La Roche | Indole derivatives and method for producing same |
| GB886684A (en) * | 1957-09-17 | 1962-01-10 | Upjohn Co | Improvements in or relating to heterocyclic compounds and the manufacture thereof |
| GB851780A (en) * | 1958-02-25 | 1960-10-19 | Rhone Poulenc Sa | New indole derivatives |
| US3037031A (en) * | 1959-08-04 | 1962-05-29 | Warner Lambert Pharmaceutical | Derivatives of 3-(2-aminoalkyl)-5-indolol and process therefor |
| GB893707A (en) * | 1960-03-01 | 1962-04-11 | Roche Products Ltd | Novel tryptamine derivatives and a process for the manufacture thereof |
| GB966562A (en) * | 1961-04-06 | 1964-08-12 | Parke Davis & Co | Amine compounds and means of producing the same |
| ZA795239B (en) * | 1978-10-12 | 1980-11-26 | Glaxo Group Ltd | Heterocyclic compounds |
| ZW19381A1 (en) * | 1980-08-12 | 1983-03-09 | Glaxo Group Ltd | Heterocyclic compounds |
| US4803218A (en) * | 1982-09-29 | 1989-02-07 | Mcneilab, Inc. | 3-aminoalkyl-1H-indole-5-urea and amide derivatives |
| GB8600397D0 (en) * | 1986-01-08 | 1986-02-12 | Glaxo Group Ltd | Chemical compounds |
| IL96891A0 (en) * | 1990-01-17 | 1992-03-29 | Merck Sharp & Dohme | Indole-substituted five-membered heteroaromatic compounds,their preparation and pharmaceutical compositions containing them |
| SI21560B (sl) * | 1990-06-07 | 2005-04-30 | Astrazeneca Ab | 3,5-disubstituirani indolni derivati kot "5-HT1-podobni" receptorski agonisti |
| DK158590D0 (da) * | 1990-07-02 | 1990-07-02 | Lundbeck & Co As H | Indolderivater |
| US5578612A (en) * | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
| WO1992006973A1 (en) * | 1990-10-15 | 1992-04-30 | Pfizer Inc. | Indole derivatives |
| US5545644A (en) * | 1990-10-15 | 1996-08-13 | Pfizer Inc. | Indole derivatives |
| US5559129A (en) * | 1990-10-15 | 1996-09-24 | Pfizer Inc | Indole derivatives |
| US5607951A (en) * | 1990-10-15 | 1997-03-04 | Pfizer Inc | Indole derivatives |
| US5208248A (en) * | 1991-01-11 | 1993-05-04 | Merck Sharpe & Dohme, Ltd. | Indazole-substituted five-membered heteroaromatic compounds |
| CZ283018B6 (cs) * | 1991-02-01 | 1997-12-17 | Merck Sharp And Dohme Limited | Deriváty imidazolu, triazolu a tetrazolu a farmaceutické přípravky na jejich bázi |
| EP0619805B1 (en) * | 1991-11-25 | 2000-03-15 | Pfizer Inc. | 5-(hetero- or carbocyclylamino)-indole derivatives, their preparation and their use as 5-ht1 agonists |
| GB9201038D0 (en) * | 1992-01-16 | 1992-03-11 | Glaxo Group Ltd | Chemical compounds |
| US5409941A (en) * | 1992-02-03 | 1995-04-25 | Pfizer Inc. | 5-heteroyl indole derivatives |
| TW288010B (ja) * | 1992-03-05 | 1996-10-11 | Pfizer | |
| US5747501A (en) * | 1992-04-07 | 1998-05-05 | Pfizer, Inc. | Indole derivatives |
| UA34452C2 (uk) * | 1992-04-10 | 2001-03-15 | Пфайзер Інк. | Похідні ациламіноіндолу, що проявляють серотонінову 5-нт1 агоністичну активність та похідні аміноіндолу як проміжні сполуки |
| GB9207930D0 (en) * | 1992-04-10 | 1992-05-27 | Pfizer Ltd | Indoles |
| GB9208161D0 (en) * | 1992-04-14 | 1992-05-27 | Pfizer Ltd | Indoles |
| GB9210400D0 (en) * | 1992-05-15 | 1992-07-01 | Merck Sharp & Dohme | Therapeutic agents |
| TW251284B (ja) * | 1992-11-02 | 1995-07-11 | Pfizer | |
| GB9226532D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
| FR2701026B1 (fr) * | 1993-02-02 | 1995-03-31 | Adir | Nouveaux dérivés de l'indole, de l'indazole et du benzisoxazole, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| CA2157397C (en) * | 1993-04-22 | 1999-07-06 | Martin James Wythes | Indole derivatives as 5-ht1-like agonists for use in migraine |
| AP486A (en) * | 1993-04-27 | 1996-04-16 | Pfizer | Indole derivatives. |
| CZ59996A3 (en) * | 1993-08-31 | 1996-06-12 | Pfizer | 5-arylindole derivatives per se and for treating diseases, intermediates for their preparation and pharmaceutical compositions based thereon |
-
1994
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- 1994-07-04 KR KR1019960701010A patent/KR100191973B1/ko not_active IP Right Cessation
- 1994-07-04 BR BR9407402A patent/BR9407402A/pt not_active Application Discontinuation
- 1994-07-04 DE DE69413240T patent/DE69413240T2/de not_active Expired - Fee Related
- 1994-07-04 DK DK94918494T patent/DK0716649T3/da active
- 1994-07-04 WO PCT/IB1994/000195 patent/WO1995006636A1/en not_active Application Discontinuation
- 1994-07-04 ES ES94918494T patent/ES2122289T3/es not_active Expired - Lifetime
- 1994-07-04 EP EP94918494A patent/EP0716649B1/en not_active Expired - Lifetime
- 1994-07-04 CN CN94193224A patent/CN1129933A/zh active Pending
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- 1994-07-04 AT AT94918494T patent/ATE170836T1/de not_active IP Right Cessation
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- 1994-08-28 EG EG52794A patent/EG20547A/xx active
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