PT2285784E - 2-metil-1-(fenilsulfonil)-4-(piperazin-1-il)-1hbenzimidazol como ligando de 5-hidroxitriptamina-6 - Google Patents
2-metil-1-(fenilsulfonil)-4-(piperazin-1-il)-1hbenzimidazol como ligando de 5-hidroxitriptamina-6 Download PDFInfo
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- PT2285784E PT2285784E PT09752080T PT09752080T PT2285784E PT 2285784 E PT2285784 E PT 2285784E PT 09752080 T PT09752080 T PT 09752080T PT 09752080 T PT09752080 T PT 09752080T PT 2285784 E PT2285784 E PT 2285784E
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Classifications
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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Landscapes
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- Bioinformatics & Cheminformatics (AREA)
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- Addiction (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11329608P | 2008-11-11 | 2008-11-11 |
Publications (1)
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| PT2285784E true PT2285784E (pt) | 2012-09-19 |
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| PT09752080T PT2285784E (pt) | 2008-11-11 | 2009-11-10 | 2-metil-1-(fenilsulfonil)-4-(piperazin-1-il)-1hbenzimidazol como ligando de 5-hidroxitriptamina-6 |
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7951805B2 (en) * | 2004-09-20 | 2011-05-31 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
| EP1804799B1 (en) * | 2004-09-20 | 2013-08-21 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| CN101083986A (zh) * | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 双环杂环衍生物及其作为硬脂酰CoA去饱和酶(SCD)抑制剂的用途 |
| CA2580856A1 (en) * | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| 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 |
| AU2015286049B2 (en) | 2014-07-08 | 2018-03-01 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic derivatives and pharmaceutical applications thereof |
| WO2017052394A1 (en) | 2015-09-23 | 2017-03-30 | Uniwersytet Jagielloński | Imidazopyridine compounds and their use as 5-ht6 receptor ligands |
| EP3530651A1 (en) * | 2018-02-21 | 2019-08-28 | Adamed sp. z o.o. | Indole and benzimidazole derivatives as dual 5-ht2a and 5-ht6 receptor antagonists |
| WO2021021951A1 (en) | 2019-07-29 | 2021-02-04 | Vanderbilt University | Wdr5-myc inhibitors |
| EP4121413A4 (en) * | 2020-04-22 | 2024-04-17 | Recurium IP Holdings, LLC | PREPARATION OF A SELECTIVE ESTROGEN RECEPTOR DEGRADING AGENT |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2194984C (en) | 1994-07-26 | 2002-07-02 | John Eugene Macor | 4-indole derivatives as serotonin agonists and antagonists |
| US5849759A (en) * | 1995-12-08 | 1998-12-15 | Berlex Laboratories, Inc. | Naphthyl-substituted benzimidazole derivatives as anti-coagulants |
| DZ2376A1 (fr) * | 1996-12-19 | 2002-12-28 | Smithkline Beecham Plc | Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant. |
| IL133870A0 (en) | 1997-07-11 | 2001-04-30 | Smithkline Beecham Plc | Sulphonamide derivatives being 5-ht6 receptor antagonists and process for their preparation |
| GB9716656D0 (en) * | 1997-08-07 | 1997-10-15 | Zeneca Ltd | Chemical compounds |
| DK0930302T3 (da) | 1998-01-16 | 2003-07-21 | Hoffmann La Roche | Benzosulfonderivater |
| US6251893B1 (en) | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
| ES2192394T3 (es) * | 1998-08-10 | 2003-10-01 | Winston Pharmateuticals Llc | Profarmacos de inhibidores de la bomba de protones. |
| GB9818916D0 (en) * | 1998-08-28 | 1998-10-21 | Smithkline Beecham Plc | Use |
| SE0002754D0 (sv) | 2000-07-21 | 2000-07-21 | Pharmacia & Upjohn Ab | New pharmaceutical combination formulation and method of treatment with the combination |
| SE0003810D0 (sv) * | 2000-10-20 | 2000-10-20 | Pharmacia Ab | Novel compounds their use and preparations |
| KR100823908B1 (ko) * | 2000-10-20 | 2008-04-21 | 바이오비트럼 에이비(피유비엘) | 2-, 3-, 4-, 또는 5-치환-ｎ1-(벤젠술포닐)인돌 및 이의치료 용도 |
| US7034029B2 (en) * | 2000-11-02 | 2006-04-25 | Wyeth | 1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands |
| EP1343756A2 (en) * | 2000-11-02 | 2003-09-17 | Wyeth | 1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands |
| MXPA03011638A (es) * | 2001-06-15 | 2004-04-02 | Hoffmann La Roche | Nuevos derivados de 4-piperazinil indol con afinidad por el receptor 5-ht6. |
| 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 |
| WO2003026665A1 (en) | 2001-09-26 | 2003-04-03 | Bayer Pharmaceuticals Corporation | 2-phenylamino-4-(5-pyrazolylamino)-pyrimidine derivatives as kinase inhibitors, in particular, src kinase inhibitors |
| AU2003284142A1 (en) | 2002-10-15 | 2004-05-04 | Synta Pharmaceuticals Corp | Aromatic bicyclic heterocyles to modulate 1L-12 production |
| TWI380816B (zh) | 2004-04-13 | 2013-01-01 | Synta Pharmaceuticals Corp | 抑制介白素-１２（ｉｌ-１２）生成之二鹽抑制劑 |
| RU2007107177A (ru) | 2004-07-28 | 2008-09-10 | Айрм Ллк (Bm) | Соединения и композиции, как модуляторы ядерных рецепторов стероидных гормонов |
| US7713954B2 (en) * | 2004-09-30 | 2010-05-11 | Roche Palo Alto Llc | Compositions and methods for treating cognitive disorders |
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