RU2324693C2 - 4-пиперазинилбензолсульфонилиндолы, характеризующиеся сродством к рецептору 5-нт6 - Google Patents
4-пиперазинилбензолсульфонилиндолы, характеризующиеся сродством к рецептору 5-нт6 Download PDFInfo
- Publication number
- RU2324693C2 RU2324693C2 RU2005115115/04A RU2005115115A RU2324693C2 RU 2324693 C2 RU2324693 C2 RU 2324693C2 RU 2005115115/04 A RU2005115115/04 A RU 2005115115/04A RU 2005115115 A RU2005115115 A RU 2005115115A RU 2324693 C2 RU2324693 C2 RU 2324693C2
- Authority
- RU
- Russia
- Prior art keywords
- indole
- ylbenzenesulfonyl
- piperazin
- chloro
- compound
- Prior art date
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- 108091005435 5-HT6 receptors Proteins 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 155
- 239000001257 hydrogen Substances 0.000 claims abstract description 86
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 86
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 37
- 150000002367 halogens Chemical class 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 36
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 239000012453 solvate Substances 0.000 claims abstract description 12
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims abstract description 5
- -1 n is 1 Chemical compound 0.000 claims description 56
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- YYTPFJPXIXRCIO-UHFFFAOYSA-N 2-(4-piperazin-1-ylphenyl)sulfonyl-1h-indole Chemical compound C=1C2=CC=CC=C2NC=1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 YYTPFJPXIXRCIO-UHFFFAOYSA-N 0.000 claims description 6
- ISGSSIOGLLTWCV-UHFFFAOYSA-N 5-bromo-3-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]sulfonyl-1h-indole Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)C=2C3=CC(Br)=CC=C3NC=2)C(Cl)=C1 ISGSSIOGLLTWCV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- IJDFGMWOCZUGIA-UHFFFAOYSA-N 5-fluoro-1-(4-piperazin-1-ylphenyl)sulfonylindole Chemical compound C1=CC2=CC(F)=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 IJDFGMWOCZUGIA-UHFFFAOYSA-N 0.000 claims description 5
- AFBFLUVKIUCKDX-UHFFFAOYSA-N 7-bromo-3-(4-piperazin-1-ylphenyl)sulfonyl-1h-indole Chemical compound C=1NC=2C(Br)=CC=CC=2C=1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 AFBFLUVKIUCKDX-UHFFFAOYSA-N 0.000 claims description 5
- OOMFLFHKRGRSPZ-UHFFFAOYSA-N 1-(4-piperazin-1-ylphenyl)sulfonylindole Chemical compound C1=CC2=CC=CC=C2N1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 OOMFLFHKRGRSPZ-UHFFFAOYSA-N 0.000 claims description 4
- RYDIZDOFZGMJKT-UHFFFAOYSA-N 3-(4-piperazin-1-ylphenyl)sulfonyl-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 RYDIZDOFZGMJKT-UHFFFAOYSA-N 0.000 claims description 4
- CTRHPFJATTYDGB-UHFFFAOYSA-N 5-bromo-1-methyl-3-(4-piperazin-1-ylphenyl)sulfonylindole Chemical compound C12=CC(Br)=CC=C2N(C)C=C1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 CTRHPFJATTYDGB-UHFFFAOYSA-N 0.000 claims description 4
- JLXBHKYSTCWZTK-UHFFFAOYSA-N 5-bromo-3-(4-piperazin-1-ylphenyl)sulfonyl-1h-indole Chemical compound C12=CC(Br)=CC=C2NC=C1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 JLXBHKYSTCWZTK-UHFFFAOYSA-N 0.000 claims description 4
- GNSVEUXJFZGGOY-UHFFFAOYSA-N 5-fluoro-1-[4-(4-methylpiperazin-1-yl)phenyl]sulfonylindole Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)N2C3=CC=C(F)C=C3C=C2)C=C1 GNSVEUXJFZGGOY-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
- WLMHUVOJWSRCKQ-UHFFFAOYSA-N 1-methyl-3-(4-piperazin-1-ylphenyl)sulfonylindole Chemical compound C12=CC=CC=C2N(C)C=C1S(=O)(=O)C(C=C1)=CC=C1N1CCNCC1 WLMHUVOJWSRCKQ-UHFFFAOYSA-N 0.000 claims description 3
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- LGTAZVZDQDIXDZ-UHFFFAOYSA-N 3-[2-chloro-4-(4-methylpiperazin-1-yl)phenyl]sulfonyl-1h-indole Chemical compound C1CN(C)CCN1C1=CC=C(S(=O)(=O)C=2C3=CC=CC=C3NC=2)C(Cl)=C1 LGTAZVZDQDIXDZ-UHFFFAOYSA-N 0.000 claims description 3
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- IPBVNPXQWQGGJP-UHFFFAOYSA-N phenyl acetate Chemical group CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
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- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
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- 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
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
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- OWPIFQXNMLDXKW-UHFFFAOYSA-N tert-butyl indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 OWPIFQXNMLDXKW-UHFFFAOYSA-N 0.000 description 1
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- 238000012360 testing method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- General Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Psychology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41936902P | 2002-10-18 | 2002-10-18 | |
| US60/419,369 | 2002-10-18 |
Publications (2)
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| RU2005115115A RU2005115115A (ru) | 2006-01-20 |
| RU2324693C2 true RU2324693C2 (ru) | 2008-05-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2005115115/04A RU2324693C2 (ru) | 2002-10-18 | 2003-10-13 | 4-пиперазинилбензолсульфонилиндолы, характеризующиеся сродством к рецептору 5-нт6 |
Country Status (21)
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| EP (1) | EP1556037B1 (enExample) |
| JP (1) | JP2006505559A (enExample) |
| KR (1) | KR20050073560A (enExample) |
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| AT (1) | ATE344030T1 (enExample) |
| AU (1) | AU2003283265B2 (enExample) |
| BR (1) | BR0315317A (enExample) |
| CA (1) | CA2501172A1 (enExample) |
| DE (1) | DE60309498T2 (enExample) |
| ES (1) | ES2274285T3 (enExample) |
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| MX (1) | MXPA05004128A (enExample) |
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| PE (1) | PE20040691A1 (enExample) |
| PL (1) | PL376479A1 (enExample) |
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| YU96103A (sh) * | 2001-06-07 | 2006-08-17 | F.Hoffmann-La Roche Ag. | Novi derivati indola sa afinitetom za 5-ht6 receptor |
| BRPI0308696B8 (pt) | 2002-03-27 | 2021-05-25 | Axovant Sciences Gmbh | composto derivado de quinolina, seu processo de preparação, sua composição farmacêutica e seus usos |
| BRPI0412263B1 (pt) | 2003-07-22 | 2019-10-15 | Arena Pharmaceuticals, Inc. | Derivados de diaril e aril heteroaril uréia, uso e composição farmacêutica contendo os mesmos, bem como processo para preparação da dita composição |
| SG184755A1 (en) | 2004-03-15 | 2012-10-30 | Ptc Therapeutics Inc | Carboline derivatives useful in the inhibition of angiogenesis |
| US7767689B2 (en) | 2004-03-15 | 2010-08-03 | Ptc Therapeutics, Inc. | Carboline derivatives useful in the treatment of cancer |
| US8076353B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Inhibition of VEGF translation |
| US8076352B2 (en) | 2004-03-15 | 2011-12-13 | Ptc Therapeutics, Inc. | Administration of carboline derivatives useful in the treatment of cancer and other diseases |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| CA2573185A1 (en) | 2004-07-14 | 2006-02-23 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| AR052308A1 (es) * | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto |
| US7645881B2 (en) | 2004-07-22 | 2010-01-12 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7713954B2 (en) * | 2004-09-30 | 2010-05-11 | Roche Palo Alto Llc | Compositions and methods for treating cognitive disorders |
| WO2006037482A2 (en) | 2004-09-30 | 2006-04-13 | F. Hoffmann-La Roche Ag | Compositions and methods for treating cognitive disorders |
| EP1919896B1 (en) | 2005-08-12 | 2009-12-23 | Suven Life Sciences Limited | Aminoaryl sulphonamide derivatives as functional 5-ht6 ligands. |
| JP5146766B2 (ja) * | 2005-08-15 | 2013-02-20 | ワイス・エルエルシー | ５−ヒドロキシトリプタミン−６リガンドとしての置換−３−スルホニルインダゾール誘導体 |
| WO2007020654A1 (en) | 2005-08-16 | 2007-02-22 | Suven Life Sciences | An improved process for the preparation of losartan |
| JP2009523734A (ja) * | 2006-01-13 | 2009-06-25 | ワイス | ５−ヒドロキシトリプタミン受容体のためのリガンドとしてのスルホニル置換された１ｈ−インドール |
| BRPI0718584A2 (pt) * | 2006-11-09 | 2014-03-11 | Hoffmann La Roche | Arilsulfonila pirrolidinas como inbidores de 5-ht6 |
| KR101132577B1 (ko) | 2007-01-10 | 2012-04-05 | 에프. 호프만-라 로슈 아게 | 키마아제 억제제로서의 술폰아미드 유도체 |
| EA017154B1 (ru) * | 2007-10-26 | 2012-10-30 | Сувен Лайф Сайенсиз Лимитед | Аминоарилсульфонамидные соединения и их применение в качестве 5-нтлигандов |
| WO2009074607A1 (en) | 2007-12-12 | 2009-06-18 | Glaxo Group Limited | Combinations comprising 3-phenylsulfonyl-8-piperazinyl-1yl-quinoline |
| WO2009123714A2 (en) | 2008-04-02 | 2009-10-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| US8318725B2 (en) | 2008-09-17 | 2012-11-27 | Suven Life Sciences Limited | Aryl indolyl sulfonamide compounds and their use as 5-HT6 ligands |
| US9126946B2 (en) | 2008-10-28 | 2015-09-08 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto |
| US8575186B2 (en) | 2009-10-05 | 2013-11-05 | Albany Molecular Research, Inc. | Epiminocycloalkyl[b] indole derivatives as serotonin sub-type 6 (5-HT6) modulators and uses thereof |
| AU2012207335A1 (en) | 2011-01-19 | 2013-07-25 | Albany Molecular Research, Inc. | Benzofuro[3,2-c] pyridines and related analogs as serotonin sub-type 6 (5-HT6) modulators for the treatment of obesity, metabolic syndrome, cognition and schizophrenia |
| US9801863B2 (en) | 2012-04-16 | 2017-10-31 | Case Western Reserve University | Inhibitors of short-chain dehydrogenase activity for modulating hematopoietic stem cells and hematopoiesis |
| PT2838533T (pt) | 2012-04-16 | 2017-11-22 | Univ Texas | Composições e métodos de modulação da atividade de 15-pgdh |
| CN104276993B (zh) * | 2013-07-12 | 2019-03-15 | 广东东阳光药业有限公司 | 吲哚衍生物及其在药物上的应用 |
| AU2014342811B2 (en) | 2013-10-15 | 2019-01-03 | Board Of Regents Of The University Of Texas System | Compositions and methods of modulating short-chain dehydrogenase activity |
| CN104557726B (zh) * | 2013-10-19 | 2019-05-24 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| EP3083588B1 (en) | 2013-12-20 | 2020-12-09 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic compounds and their application in pharmaceuticals |
| JP6515175B2 (ja) * | 2014-07-08 | 2019-05-15 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドＳｕｎｓｈｉｎｅ Ｌａｋｅ Ｐｈａｒｍａ Ｃｏ．，Ｌｔｄ． | 芳香族ヘテロ環誘導体及びその医薬的適用 |
| EP4119141A1 (en) | 2015-06-12 | 2023-01-18 | Axovant Sciences GmbH | Nelotanserin for the prophylaxis and treatment of rem sleep behavior disorder |
| EP3322415A4 (en) | 2015-07-15 | 2019-03-13 | Axovant Sciences GmbH | DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR FOR PROPHYLAXIS AND TREATMENT OF HALLUCINATIONS RELATED TO A NEUROGENERATIVE DISEASE |
| EP3548035A4 (en) | 2016-11-30 | 2020-07-22 | Case Western Reserve University | COMBINATIONS OF 15-PGDH INHIBITORS WITH CORCOSTEROIDS AND / OR TNF INHIBITORS AND THEIR USES |
| CN110573154A (zh) | 2017-02-06 | 2019-12-13 | 卡斯西部储备大学 | 调节短链脱氢酶活性的组合物和方法 |
| CN109232362B (zh) * | 2017-07-10 | 2022-12-27 | 广东东阳光药业有限公司 | 芳杂环类衍生物及其在药物上的应用 |
| EA202191422A1 (ru) | 2018-11-21 | 2021-10-21 | Кейс Вестерн Ризерв Юниверсити | Композиции и способы модулирования активности короткоцепочечной дегидрогеназы |
| AU2022380979A1 (en) | 2021-11-02 | 2024-06-06 | Flare Therapeutics Inc. | Pparg inverse agonists and uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9116732D0 (en) | 1991-08-02 | 1991-09-18 | Fujisawa Pharmaceutical Co | Indole derivatives |
| FR2729144A1 (fr) | 1995-01-06 | 1996-07-12 | Smithkline Beecham Lab | Nouvelles diamines, leur procede de preparation et leur utilisation en tant que medicaments et notamment en tant qu' agents anti-arythmiques |
| DZ2376A1 (fr) | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
| WO1999002502A2 (en) * | 1997-07-11 | 1999-01-21 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| GB9801392D0 (en) * | 1998-01-22 | 1998-03-18 | Smithkline Beecham Plc | Novel compounds |
| WO2000058304A1 (en) | 1999-03-26 | 2000-10-05 | Shionogi & Co., Ltd. | Heterocyclic sulfonamide derivatives |
| DK1259485T3 (da) | 2000-02-29 | 2006-04-10 | Millennium Pharm Inc | Benzamider og beslægtede inhibitorer for faktor Xa |
| NZ524675A (en) * | 2000-10-20 | 2004-09-24 | Biovitrum Ab | 2-, 3-, 4-, or 5-substituted-N1-(benzensulfonyl) indoles and their use in therapy |
| WO2002041889A2 (en) * | 2000-11-24 | 2002-05-30 | Smithkline Beecham P.L.C. | Indolsulfonyl compounds useful in the treatment of cns disorders |
| CN1321110C (zh) * | 2001-06-15 | 2007-06-13 | 弗·哈夫曼-拉罗切有限公司 | 具有5－ht6受体亲和力的4－哌嗪基吲哚衍生物 |
| JP4390698B2 (ja) * | 2002-06-05 | 2009-12-24 | エフ．ホフマン−ラ ロシュ アーゲー | Ｃｎｓ障害の処置のための５−ｈｔ６レセプターモジュレーターとしての１−スルホニル−４−アミノアルコキシインドール誘導体 |
| US7943639B2 (en) | 2002-06-20 | 2011-05-17 | Proximagen Limited | Compounds |
| JP4267573B2 (ja) * | 2002-09-17 | 2009-05-27 | エフ．ホフマン−ラ ロシュ アーゲー | ２，４−置換インドールおよびそれらの５−ｈｔ６モジュレーターとしての使用 |
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- 2003-10-13 EP EP03775181A patent/EP1556037B1/en not_active Expired - Lifetime
- 2003-10-13 CA CA002501172A patent/CA2501172A1/en not_active Abandoned
- 2003-10-13 KR KR1020057006683A patent/KR20050073560A/ko not_active Ceased
- 2003-10-13 CN CNB2003801014548A patent/CN1309384C/zh not_active Expired - Fee Related
- 2003-10-13 ES ES03775181T patent/ES2274285T3/es not_active Expired - Lifetime
- 2003-10-13 PL PL03376479A patent/PL376479A1/xx not_active Application Discontinuation
- 2003-10-13 JP JP2004544204A patent/JP2006505559A/ja active Pending
- 2003-10-13 WO PCT/EP2003/011323 patent/WO2004035047A1/en not_active Ceased
- 2003-10-13 BR BR0315317-7A patent/BR0315317A/pt not_active IP Right Cessation
- 2003-10-13 RU RU2005115115/04A patent/RU2324693C2/ru not_active IP Right Cessation
- 2003-10-13 AT AT03775181T patent/ATE344030T1/de not_active IP Right Cessation
- 2003-10-13 MX MXPA05004128A patent/MXPA05004128A/es active IP Right Grant
- 2003-10-13 DE DE60309498T patent/DE60309498T2/de not_active Expired - Lifetime
- 2003-10-13 AU AU2003283265A patent/AU2003283265B2/en not_active Ceased
- 2003-10-14 TW TW092128412A patent/TW200418456A/zh unknown
- 2003-10-15 PE PE2003001052A patent/PE20040691A1/es not_active Application Discontinuation
- 2003-10-15 PA PA20038586401A patent/PA8586401A1/es unknown
- 2003-10-16 AR ARP030103764A patent/AR041635A1/es not_active Application Discontinuation
- 2003-10-16 UY UY28026A patent/UY28026A1/es not_active Application Discontinuation
- 2003-10-16 US US10/687,091 patent/US7022708B2/en not_active Expired - Fee Related
- 2003-10-17 GT GT200300226A patent/GT200300226A/es unknown
Also Published As
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| MXPA05004128A (es) | 2005-06-22 |
| KR20050073560A (ko) | 2005-07-14 |
| ATE344030T1 (de) | 2006-11-15 |
| ES2274285T3 (es) | 2007-05-16 |
| AU2003283265A1 (en) | 2004-05-04 |
| DE60309498D1 (de) | 2006-12-14 |
| UY28026A1 (es) | 2004-04-30 |
| TW200418456A (en) | 2004-10-01 |
| CN1705480A (zh) | 2005-12-07 |
| EP1556037A1 (en) | 2005-07-27 |
| US7022708B2 (en) | 2006-04-04 |
| AU2003283265B2 (en) | 2009-03-05 |
| JP2006505559A (ja) | 2006-02-16 |
| EP1556037B1 (en) | 2006-11-02 |
| GT200300226A (es) | 2004-10-18 |
| PL376479A1 (en) | 2005-12-27 |
| PA8586401A1 (es) | 2005-08-04 |
| RU2005115115A (ru) | 2006-01-20 |
| CA2501172A1 (en) | 2004-08-29 |
| WO2004035047A1 (en) | 2004-04-29 |
| BR0315317A (pt) | 2005-09-06 |
| AR041635A1 (es) | 2005-05-26 |
| DE60309498T2 (de) | 2007-08-30 |
| US20040087593A1 (en) | 2004-05-06 |
| PE20040691A1 (es) | 2004-10-16 |
| CN1309384C (zh) | 2007-04-11 |
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| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20101014 |