TW201514154A - 適用於治療對多巴胺d3受體調節有反應的病症之醯胺基環烷基化合物 - Google Patents
適用於治療對多巴胺d3受體調節有反應的病症之醯胺基環烷基化合物 Download PDFInfo
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- TW201514154A TW201514154A TW103109325A TW103109325A TW201514154A TW 201514154 A TW201514154 A TW 201514154A TW 103109325 A TW103109325 A TW 103109325A TW 103109325 A TW103109325 A TW 103109325A TW 201514154 A TW201514154 A TW 201514154A
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- butyl
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- piperazin
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/495—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
Landscapes
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- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US201361786869P | 2013-03-15 | 2013-03-15 | |
| US201361918524P | 2013-12-19 | 2013-12-19 |
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| US (1) | US9388148B2 (enExample) |
| EP (1) | EP2970146B1 (enExample) |
| JP (1) | JP2016514117A (enExample) |
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| MX (1) | MX2015012184A (enExample) |
| TW (1) | TW201514154A (enExample) |
| UY (1) | UY35420A (enExample) |
| WO (1) | WO2014140246A1 (enExample) |
Cited By (1)
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| TWI873212B (zh) * | 2019-10-29 | 2025-02-21 | 大陸商上海翰森生物醫藥科技有限公司 | 四員環類衍生物調節劑、其製備方法和應用 |
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| US9376396B2 (en) | 2012-10-22 | 2016-06-28 | AbbVie Deutschland GmbH & Co. KG | Acylaminocycloalkyl compounds suitable for treating disorders that respond to modulation of dopamine D3 receptor |
| UY35420A (es) | 2013-03-15 | 2014-10-31 | Abbvie Inc | Compuestos de acilaminocicloalquilo apropiados para tratar trastornos que responden a la modulación del receptor de dopamina d3 |
| AR095264A1 (es) * | 2013-03-15 | 2015-09-30 | Abbvie Deutschland | Compuestos de acilaminocicloalquilo apropiados para tratar trastornos que responden a la modulación del receptor de dopamina d3 |
| WO2018021447A1 (ja) | 2016-07-28 | 2018-02-01 | 塩野義製薬株式会社 | ドーパミンd3受容体拮抗作用を有する含窒素縮環化合物 |
| US11447484B2 (en) | 2018-01-26 | 2022-09-20 | Shionogi & Co., Ltd. | Cyclic compound having dopamine D3 receptor antagonistic effect |
| AU2019211806A1 (en) | 2018-01-26 | 2020-07-30 | Shionogi & Co., Ltd. | Condensed cyclic compound having dopamine D3 receptor antagonism |
| WO2020156312A1 (zh) * | 2019-01-30 | 2020-08-06 | 江苏豪森药业集团有限公司 | 一种多环类衍生物调节剂、其制备方法和应用 |
| CN112239433B (zh) * | 2019-07-17 | 2024-05-14 | 北京盈科瑞创新药物研究有限公司 | 一种环己烷衍生物、制备方法及其应用 |
| US20230076435A1 (en) * | 2019-10-29 | 2023-03-09 | Shanghai Hansoh Biomedical Co., Ltd. | Modifier of four-membered ring derivative, preparation method and application thereof |
| CN113754580B (zh) * | 2020-06-05 | 2023-04-25 | 上海中泽医药科技有限公司 | 一种吡啶吗啉类化合物、其制备方法及其应用 |
| EP4332093A4 (en) * | 2021-04-28 | 2025-04-30 | Shanghai Hansoh Biomedical Co., Ltd. | Salt with polycyclic piperazine derivative, crystalline form thereof, production process therefor and use thereof |
Family Cites Families (18)
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|---|---|---|---|---|
| DE10311065A1 (de) | 2003-03-13 | 2004-09-23 | Abbott Gmbh & Co. Kg | Pyrimidin-2-on-Verbindungen und ihre therapeutische Verwendung |
| JP2004359689A (ja) | 2003-06-05 | 2004-12-24 | Abbott Gmbh & Co Kg | ドーパミンd3受容体のモジュレーションに反応する障害の治療に適するトリアゾール化合物 |
| DE102004027358A1 (de) | 2004-06-04 | 2005-12-29 | Abbott Gmbh & Co. Kg | Pyrimidinverbindungen und ihre Verwendung |
| DE102004027359A1 (de) | 2004-06-04 | 2005-12-29 | Abbott Gmbh & Co. Kg | Pyridin-2-onverbindungen und deren Verwendung |
| ES2340941T3 (es) | 2004-08-09 | 2010-06-11 | ABBOTT GMBH & CO. KG | Compuestos de 4-piperazinil-pirimidina adecuados para tretar trastornos que responden a modulacion del receptor d 3 de dopamina. |
| DE102004061593A1 (de) * | 2004-12-21 | 2006-06-22 | Abbott Gmbh & Co. Kg | Substituierte N-heterocyclische Verbindungen und ihre therapeutische Verwendung |
| HUP0500170A3 (en) | 2005-02-03 | 2007-11-28 | Richter Gedeon Nyrt | Piperazine derivatives, process for producing them and pharmaceutical compositions containing them |
| EP1870405A1 (en) * | 2006-06-22 | 2007-12-26 | Bioprojet | Carbonylated (Aza)cyclohexanes as dopamine D3 receptor ligands |
| WO2008065500A2 (en) | 2006-11-30 | 2008-06-05 | Pfizer Products Inc. | Heteroaryl amides as type i glycine transport inhibitors |
| WO2009003868A2 (en) | 2007-07-02 | 2009-01-08 | F. Hoffmann-La Roche Ag | 2 -imidazolines having a good affinity to the trace amine associated receptors (taars) |
| PA8802101A1 (es) | 2007-11-02 | 2009-08-26 | Abbott Gmbh & Co Kg | Compuestos de 1,2,4-3,5-diona adecuados para el tratamiento de trastornos que responden a la modulación del receptor de dopamina d3 |
| US7875610B2 (en) | 2007-12-03 | 2011-01-25 | Richter Gedeon Nyrt. | Pyrimidinyl-piperazines useful as D3/D2 receptor ligands |
| BRPI0918949A2 (pt) * | 2008-09-22 | 2019-09-24 | Hoffmann La Roche | moduladores de receptores de 5-ht2a e piperazina d3 |
| WO2010034648A1 (en) | 2008-09-23 | 2010-04-01 | F. Hoffmann-La Roche Ag | Pyridinylpiperazin derivatives useful as modulators of dopamine d3 receptors |
| US8586579B2 (en) | 2010-06-21 | 2013-11-19 | Hoffmann-La Roche Inc. | Anellated pyridine compounds |
| US8470828B2 (en) * | 2010-07-06 | 2013-06-25 | Hoffmann-La Roche Inc. | Anellated pyridine compounds |
| US9376396B2 (en) | 2012-10-22 | 2016-06-28 | AbbVie Deutschland GmbH & Co. KG | Acylaminocycloalkyl compounds suitable for treating disorders that respond to modulation of dopamine D3 receptor |
| UY35420A (es) | 2013-03-15 | 2014-10-31 | Abbvie Inc | Compuestos de acilaminocicloalquilo apropiados para tratar trastornos que responden a la modulación del receptor de dopamina d3 |
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- 2014-03-13 UY UY0001035420A patent/UY35420A/es not_active Application Discontinuation
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- 2014-03-14 CA CA2902656A patent/CA2902656A1/en not_active Abandoned
- 2014-03-14 TW TW103109325A patent/TW201514154A/zh unknown
- 2014-03-14 AU AU2014230215A patent/AU2014230215A1/en not_active Abandoned
- 2014-03-14 CN CN201480026453.XA patent/CN105339357A/zh active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI873212B (zh) * | 2019-10-29 | 2025-02-21 | 大陸商上海翰森生物醫藥科技有限公司 | 四員環類衍生物調節劑、其製備方法和應用 |
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| EP2970146A1 (en) | 2016-01-20 |
| CN105339357A (zh) | 2016-02-17 |
| US9388148B2 (en) | 2016-07-12 |
| CA2902656A1 (en) | 2014-09-18 |
| JP2016514117A (ja) | 2016-05-19 |
| AU2014230215A1 (en) | 2015-09-03 |
| UY35420A (es) | 2014-10-31 |
| US20140303176A1 (en) | 2014-10-09 |
| MX2015012184A (es) | 2016-05-16 |
| WO2014140246A1 (en) | 2014-09-18 |
| EP2970146B1 (en) | 2017-11-01 |
| BR112015021471A2 (pt) | 2017-07-18 |
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