FI106198B - Menetelmä terapeuttisesti käyttökelpoisten 3-substituoitujen 2-karboksi-indolijohdannaisten valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten 3-substituoitujen 2-karboksi-indolijohdannaisten valmistamiseksi Download PDFInfo
- Publication number
- FI106198B FI106198B FI944800A FI944800A FI106198B FI 106198 B FI106198 B FI 106198B FI 944800 A FI944800 A FI 944800A FI 944800 A FI944800 A FI 944800A FI 106198 B FI106198 B FI 106198B
- Authority
- FI
- Finland
- Prior art keywords
- formula
- ethenyl
- compound
- dichloroindole
- carboxylic acid
- Prior art date
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- -1 3-substituted 2-carboxyindole Chemical class 0.000 title claims description 59
- 238000000034 method Methods 0.000 title claims description 33
- 238000002360 preparation method Methods 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 145
- 150000003839 salts Chemical class 0.000 claims description 37
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
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- 238000011282 treatment Methods 0.000 claims description 9
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 8
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- 210000001259 mesencephalon Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- OHKAPCLENKAVMN-UHFFFAOYSA-N methyl 3-(3-anilino-3-oxoprop-1-ynyl)-4,6-dichloro-1h-indole-2-carboxylate Chemical compound COC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C#CC(=O)NC1=CC=CC=C1 OHKAPCLENKAVMN-UHFFFAOYSA-N 0.000 description 1
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- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
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- 201000006417 multiple sclerosis Diseases 0.000 description 1
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-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
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 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
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- YNWSXIWHOSSPCO-UHFFFAOYSA-N rhodium(2+) Chemical compound [Rh+2] YNWSXIWHOSSPCO-UHFFFAOYSA-N 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
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- 229940116362 tragacanth Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- MRAZYSAHIPFJGX-UHFFFAOYSA-N trimethyl(1h-pyrazol-5-yl)silane Chemical compound C[Si](C)(C)C1=CC=NN1 MRAZYSAHIPFJGX-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 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
- C07D209/02—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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929208492A GB9208492D0 (en) | 1992-04-16 | 1992-04-16 | Heterocyclic compounds |
| GB9208492 | 1992-04-16 | ||
| PCT/EP1993/000938 WO1993021153A1 (en) | 1992-04-16 | 1993-04-15 | Indole-2-carboxylic acid derivatives |
| EP9300938 | 1993-04-15 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI944800A0 FI944800A0 (fi) | 1994-10-12 |
| FI944800A FI944800A (fi) | 1994-10-12 |
| FI106198B true FI106198B (fi) | 2000-12-15 |
Family
ID=10714220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI944800A FI106198B (fi) | 1992-04-16 | 1994-10-12 | Menetelmä terapeuttisesti käyttökelpoisten 3-substituoitujen 2-karboksi-indolijohdannaisten valmistamiseksi |
Country Status (41)
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| EP (1) | EP0568136A1 (es) |
| JP (2) | JPH0649027A (es) |
| KR (1) | KR100264114B1 (es) |
| CN (1) | CN1042331C (es) |
| AP (1) | AP480A (es) |
| AT (1) | AT403917B (es) |
| AU (1) | AU666927B2 (es) |
| BE (1) | BE1006343A5 (es) |
| BG (1) | BG62136B1 (es) |
| BR (1) | BR1100323A (es) |
| CA (3) | CA2094075A1 (es) |
| CH (1) | CH685630A5 (es) |
| CY (1) | CY2038B1 (es) |
| CZ (1) | CZ285799B6 (es) |
| DK (1) | DK169890B1 (es) |
| ES (1) | ES2105924B1 (es) |
| FI (1) | FI106198B (es) |
| FR (1) | FR2690919B1 (es) |
| GB (2) | GB9208492D0 (es) |
| GE (1) | GEP19991704B (es) |
| GR (1) | GR1001619B (es) |
| HK (1) | HK95797A (es) |
| HU (2) | HU217964B (es) |
| IL (1) | IL105412A (es) |
| IS (1) | IS3994A (es) |
| IT (1) | IT1265325B1 (es) |
| LU (1) | LU88248A1 (es) |
| MX (1) | MX9302195A (es) |
| MY (1) | MY112232A (es) |
| NO (1) | NO301879B1 (es) |
| NZ (1) | NZ247413A (es) |
| OA (1) | OA10103A (es) |
| PL (1) | PL176451B1 (es) |
| RO (1) | RO113242B1 (es) |
| RU (1) | RU2129544C1 (es) |
| SE (1) | SE504336C2 (es) |
| SK (1) | SK281941B6 (es) |
| TW (1) | TW224457B (es) |
| WO (1) | WO1993021153A1 (es) |
| ZA (1) | ZA932642B (es) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9304500D0 (en) * | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| DK0701551T3 (da) * | 1993-05-27 | 1997-10-20 | Merrell Pharma Inc | 3-(Indol-3-yl)propensyrederivater som NMDA-antagonister |
| US5519048A (en) * | 1993-05-27 | 1996-05-21 | Merrell Pharmaceuticals Inc. | 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof |
| GB9319243D0 (en) * | 1993-09-17 | 1993-11-03 | Glaxo Spa | Heterocyclic compounds |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| TW280819B (es) * | 1993-11-17 | 1996-07-11 | Sumitomo Pharma | |
| US5563157B1 (en) | 1994-10-31 | 1999-02-02 | Hoecst Marion Roussel Inc | Heterocycle substituted propenoic acid derivatives and pharmaceutical compositions thereof |
| GB9502695D0 (en) * | 1995-02-11 | 1995-03-29 | Glaxo Spa | Pharmaceutical composition |
| GB9504361D0 (en) * | 1995-03-04 | 1995-04-26 | Glaxo Spa | Heterocyclic compounds |
| US6030968A (en) * | 1996-09-17 | 2000-02-29 | The Regents Of The University Of California | Positive AMPA receptor modulation to enhance brain neurotrophic factor expression |
| CN1139572C (zh) * | 1996-09-30 | 2004-02-25 | 阿温蒂斯药物公司 | Nmda(n-甲基-d-天冬氨酸)拮抗剂 |
| US5922752A (en) * | 1997-06-11 | 1999-07-13 | Hoechst Marion Roussell, Inc. | NMDA (n-methyl-d-aspartate) antagonists |
| DK2198858T3 (da) * | 1998-03-26 | 2011-10-03 | Astellas Pharma Inc | Præparat med opretholdt frigivelse af en makrolidforbindelse såsom tacrolimus |
| US20030162825A1 (en) * | 2001-11-09 | 2003-08-28 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| CA2468544A1 (en) * | 2001-12-10 | 2003-06-19 | Amgen Inc. | Vanilloid receptor ligands |
| PA8579701A1 (es) * | 2002-08-23 | 2005-05-24 | Pfizer Prod Inc | Profarmaco inhibidor de beta-lactamasa |
| DE10306202A1 (de) | 2003-02-13 | 2004-08-26 | Grünenthal GmbH | Arzneimittel enthaltend substituierte 2-Aryl-Aminoessigsäure-Verbindungen und/oder substituierte 2-Heteroaryl-Aminoessigsäure-Verbindungen |
| CA2528065A1 (en) * | 2003-06-05 | 2004-12-16 | Pfizer Products Inc. | Beta-lactamase inhibitor prodrug |
| ES2347152T3 (es) * | 2003-11-26 | 2010-10-26 | Pfizer Products Inc. | Derivados de aminopirazol como inhibidores de gsk-3. |
| JP2007517056A (ja) * | 2003-12-29 | 2007-06-28 | セプラコア インコーポレーテッド | ピロール及びピラゾールｄａａｏ阻害剤 |
| US20060002999A1 (en) * | 2004-06-17 | 2006-01-05 | Forest Laboratories, Inc. | Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane |
| JP2009500425A (ja) | 2005-07-06 | 2009-01-08 | セプラコア インコーポレーテッド | エスゾピクロン及びトランス４−（３，４−ジクロロフェニル）−１，２，３，４−テトラヒドロ−ｎ−メチル−１−ナフタレンアミン又はトランス４−（３，４−ジクロロフェニル）−１，２，３，４−テトラヒドロ−１−ナフタレンアミンの組み合わせ、並びに閉経期並びに気分、不安、及び認知障害の治療方法 |
| RU2430913C2 (ru) * | 2006-01-06 | 2011-10-10 | Сепракор Инк. | Циклоалкиламины в качестве ингибиторов повторного поглощения моноамина |
| JP5438975B2 (ja) | 2006-01-06 | 2014-03-12 | サノビオン ファーマシューティカルズ インク | テトラロン系モノアミン再取り込み阻害剤 |
| DK2013835T3 (en) | 2006-03-31 | 2015-12-14 | Sunovion Pharmaceuticals Inc | Preparation of chiral amides and AMINES |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
| EP1942104A1 (en) | 2006-12-20 | 2008-07-09 | sanofi-aventis | Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| EP2074092A2 (en) * | 2007-01-18 | 2009-07-01 | Sepracor Inc. | Inhibitors of d-amino acid oxidase |
| MX2009012685A (es) | 2007-05-31 | 2009-12-14 | Sepracor Inc | Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina. |
| US20090247644A1 (en) * | 2008-03-28 | 2009-10-01 | Forest Laboratories Holdings Limited | Memantine formulations |
| WO2010017418A1 (en) * | 2008-08-07 | 2010-02-11 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| JP2010235597A (ja) | 2009-03-10 | 2010-10-21 | Santen Pharmaceut Co Ltd | ４，６−ジクロロ−１ｈ−インドール−２−カルボン酸誘導体又はその塩を有効成分として含有する視神経障害の予防又は治療剤 |
| WO2011017634A2 (en) * | 2009-08-07 | 2011-02-10 | Sepracore Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| US9868975B2 (en) | 2014-04-30 | 2018-01-16 | Yufeng Jane Tseng | Use of known compounds as D-amino acid oxidase inhibitors |
| CA3036250C (en) | 2016-09-14 | 2023-09-26 | Yufeng Jane Tseng | Novel substituted benzimidazole derivatives as d-amino acid oxidase (daao) inhibitors |
| AU2018284335A1 (en) | 2017-06-12 | 2020-01-30 | Glytech Llc. | Treatment of depression with NMDA antagonists and D2/5HT2A or selective 5HT2A antagonists |
| CN112707874A (zh) * | 2020-12-29 | 2021-04-27 | 广东中科药物研究有限公司 | 一种抗病毒化合物及其制备方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3010971A (en) * | 1960-08-04 | 1961-11-28 | Smith Kline French Lab | Cyclopropylamine derivatives and processes for their preparation |
| DK500285A (da) * | 1984-11-02 | 1986-05-03 | Glaxo Group Ltd | Cephalosporinantibiotika |
| US4960786A (en) * | 1989-04-24 | 1990-10-02 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| JPH0347123A (ja) * | 1989-05-05 | 1991-02-28 | G D Searle & Co | インドール―２―カルボキシレート化合物類を含有するｃｎｓ疾患治療用組成物 |
| WO1992001670A1 (en) * | 1990-07-16 | 1992-02-06 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| US5284862A (en) * | 1991-03-18 | 1994-02-08 | Warner-Lambert Company | Derivatives of 2-carboxyindoles having pharmaceutical activity |
| US5145845A (en) * | 1991-05-14 | 1992-09-08 | Warner-Lambert Co. | Substituted 2-carboxylindoles having pharmaceutical activity |
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1992
- 1992-04-16 GB GB929208492A patent/GB9208492D0/en active Pending
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1993
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- 1993-04-15 US US08/047,430 patent/US5374649A/en not_active Expired - Fee Related
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- 1993-04-15 GB GB9307808A patent/GB2266091B/en not_active Expired - Fee Related
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- 1993-04-15 CN CN93105797A patent/CN1042331C/zh not_active Expired - Fee Related
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- 1993-04-15 DK DK043193A patent/DK169890B1/da active
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- 1993-04-15 WO PCT/EP1993/000938 patent/WO1993021153A1/en active IP Right Grant
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1994
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1995
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1997
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1998
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