BRPI0617772A2 - composto, composição farmacêutica, e, uso de um composto - Google Patents
composto, composição farmacêutica, e, uso de um composto Download PDFInfo
- Publication number
- BRPI0617772A2 BRPI0617772A2 BRPI0617772-7A BRPI0617772A BRPI0617772A2 BR PI0617772 A2 BRPI0617772 A2 BR PI0617772A2 BR PI0617772 A BRPI0617772 A BR PI0617772A BR PI0617772 A2 BRPI0617772 A2 BR PI0617772A2
- Authority
- BR
- Brazil
- Prior art keywords
- diaza
- bicyclo
- nonane
- methyl
- pyridazin
- Prior art date
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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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
- A61K31/495—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
- A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
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Landscapes
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- Rheumatology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200501724 | 2005-12-06 | ||
| DKPA200501724 | 2005-12-06 | ||
| PCT/EP2006/069316 WO2007065892A1 (en) | 2005-12-06 | 2006-12-05 | Novel diazabicyclic aryl derivatives and their medical use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0617772A2 true BRPI0617772A2 (pt) | 2011-08-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0617772-7A BRPI0617772A2 (pt) | 2005-12-06 | 2006-12-05 | composto, composição farmacêutica, e, uso de um composto |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8173658B2 (enExample) |
| EP (2) | EP1963323B1 (enExample) |
| JP (1) | JP2009518357A (enExample) |
| KR (1) | KR20080079250A (enExample) |
| CN (1) | CN101305004B (enExample) |
| AT (1) | ATE473978T1 (enExample) |
| AU (1) | AU2006323986A1 (enExample) |
| BR (1) | BRPI0617772A2 (enExample) |
| CA (1) | CA2632642A1 (enExample) |
| DE (1) | DE602006015523D1 (enExample) |
| DK (1) | DK1963323T3 (enExample) |
| NZ (1) | NZ567048A (enExample) |
| RU (1) | RU2008110911A (enExample) |
| WO (1) | WO2007065892A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2641678A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3,9-diazabicyclo[3.3.1]nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| AU2007213670A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3,9-diazabicyclo[3.3.1]nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| EP1987031A1 (en) | 2006-02-10 | 2008-11-05 | NeuroSearch A/S | 3-heteroaryl- 3,9-diazabicyclo[3.3.1]nonane derivatives as nicotinic acetylcholine receptor agonists |
| WO2007093601A1 (en) | 2006-02-14 | 2007-08-23 | Neurosearch A/S | 3, 9-diazabicyclo(3.3.1)non-3-yl-aryl methanone derivatives as nicotinic acetylcholine receptor agonists |
| JP2009537599A (ja) | 2006-05-23 | 2009-10-29 | ノイロサーチ アクティーゼルスカブ | 新規8,10−ジアザ−ビシクロ[4.3.1]デカン誘導体及びそれらの医学的使用 |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| US20110142758A1 (en) * | 2008-06-10 | 2011-06-16 | Neurosearch A/S | Indolyl-pyridazinyl-diazabicyclononane derivatives in labelled and unlabelled form and their use in diagnostic methods |
| AR072297A1 (es) | 2008-06-27 | 2010-08-18 | Novartis Ag | Derivados de indol-2-il-piridin-3-ilo, composicion farmaceutica que los comprende y su uso en medicamentos para el tratamiento de enfermedades mediadas por la sintasa aldosterona. |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| US9464078B2 (en) | 2010-09-23 | 2016-10-11 | Abbvie Inc. | Monohydrate of azaadamantane derivatives |
| US8729263B2 (en) | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| JP7376471B2 (ja) | 2017-06-05 | 2023-11-08 | ピーティーシー セラピューティクス, インコーポレイテッド | ハンチントン病を処置するための化合物 |
| JP7399870B2 (ja) | 2018-03-27 | 2023-12-18 | ピーティーシー セラピューティクス, インコーポレイテッド | ハンチントン病を処置するための化合物 |
| CN108658762B (zh) * | 2018-06-12 | 2021-03-02 | 浙江凯普化工有限公司 | 一种脂环邻二酯的合成方法 |
| EA202092899A1 (ru) | 2018-06-27 | 2021-05-14 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Гетероарильные соединения для лечения болезни гентингтона |
| LT3814357T (lt) | 2018-06-27 | 2024-06-25 | Ptc Therapeutics, Inc. | Heterocikliniai ir heteroarilų junginiai, skirti hantingtono ligos gydymui |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3293251A (en) * | 1966-12-20 | Rearrangement process for j,b-diaza- bicyclo-(j,z,i)-octane derivatives | ||
| US5478939A (en) * | 1994-07-20 | 1995-12-26 | American Cyanamid Company | (R,R) and (S,S) 2,5-diazabicyclo [2,2,1]heptane derivatives |
| DK0984965T3 (da) | 1997-05-30 | 2004-09-27 | Neurosearch As | 8-azabicyclo[3.2.1]oct-2-enderivater som cholinerge ligander ved nikotin-ACh-receptorer |
| DE69811070T2 (de) * | 1997-05-30 | 2003-10-02 | Neurosearch A/S, Ballerup | 9-azabicyclo(3.3.1)non-2-ene und nonanderivate als liganden der nicotinergen rezeptoren |
| FR2786770B1 (fr) | 1998-12-04 | 2001-01-19 | Synthelabo | Derives de 1,4-diazabicyclo[3.2.2.]nonane, leur preparation et leur application en therapeutique |
| US7265115B2 (en) * | 1999-01-29 | 2007-09-04 | Abbott Laboratories | Diazabicyclic CNS active agents |
| NZ512884A (en) | 1999-01-29 | 2004-03-26 | Abbott Lab | Diazabicyclic derivatives as nicotinic acetylcholine receptor ligands |
| AU774867B2 (en) | 1999-05-04 | 2004-07-08 | Neurosearch A/S | Heteroaryl diazabicycloalkanes, their preparation and use |
| JP2003534344A (ja) | 2000-05-25 | 2003-11-18 | ターガセプト,インコーポレイテッド | ニコチン性コリン受容体リガンドとしてのヘテロアリールジアザビシクロアルカン |
| FR2809731B1 (fr) | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | Derives de 1,4-diazabicyclo-[3.2.2] nonane-pheylisoxazole, leur preparation et leur application en therapeutique |
| FR2809732B1 (fr) | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | DERIVES DE 4(-2-PHENYLTHIAZOL-5-yl)-1,4-DIAZABICYCLO-[3.2.2] NONANE, LEUR PREPARATION ET LEUR APPLICATION ENTHERAPEUTIQUE |
| WO2002002564A1 (en) * | 2000-07-04 | 2002-01-10 | Neurosearch A/S | Aryl and heteroaryl diazabicycloalkanes, their preparation and use |
| JP2004538268A (ja) | 2001-06-01 | 2004-12-24 | ニューロサーチ、アクティーゼルスカブ | Cns−モジュレーターとしての新規ヘテロアリール−ジアザビシクロアルカン類 |
| FR2832713B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(1,3,4-thiadiazol-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| FR2832712B1 (fr) | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(oxadiazol-3-yl)-1,4-diazabicyclo[3.2.2]nonane, leur preparation et leur application en therapeutique |
| CN1653068A (zh) * | 2002-05-07 | 2005-08-10 | 神经研究公司 | 新的二氮杂双环联芳基衍生物 |
| WO2004043960A1 (en) | 2002-11-11 | 2004-05-27 | Neurosearch A/S | 1,4-diazabicyclo (3,2,2)nonane derivatives, preparation and therapeutical use thereof |
| US7399765B2 (en) * | 2003-09-19 | 2008-07-15 | Abbott Laboratories | Substituted diazabicycloalkane derivatives |
| MXPA06005019A (es) * | 2003-11-03 | 2006-07-06 | Warner Lambert Co | Nuevos inhibidores de la recaptacion de norpinefrina para el tratamiento de transtornos del sistema nervioso central. |
| CN101035792B (zh) | 2004-10-20 | 2010-09-15 | 神经研究公司 | 新颖的二氮杂双环芳基衍生物和它们的医药用途 |
| ATE422499T1 (de) | 2004-11-30 | 2009-02-15 | Neurosearch As | Neuartige diazabicyclische arylderivate als cholinerge liganden |
| EP1863819B1 (en) | 2005-02-16 | 2011-01-12 | NeuroSearch A/S | Diazabicyclic aryl derivatives and their use as chinolinergic ligands at the nicotinic acetylcholine receptors |
| JP5052952B2 (ja) * | 2007-05-07 | 2012-10-17 | 東芝機械株式会社 | マイクロレンズ転写成形用ロールの製造方法および製造装置 |
| AR071997A1 (es) * | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
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- 2006-12-05 KR KR1020087013706A patent/KR20080079250A/ko not_active Withdrawn
- 2006-12-05 JP JP2008543818A patent/JP2009518357A/ja not_active Abandoned
- 2006-12-05 AU AU2006323986A patent/AU2006323986A1/en not_active Abandoned
- 2006-12-05 WO PCT/EP2006/069316 patent/WO2007065892A1/en not_active Ceased
- 2006-12-05 EP EP06830366A patent/EP1963323B1/en not_active Not-in-force
- 2006-12-05 NZ NZ567048A patent/NZ567048A/en not_active IP Right Cessation
- 2006-12-05 BR BRPI0617772-7A patent/BRPI0617772A2/pt not_active IP Right Cessation
- 2006-12-05 CN CN2006800416608A patent/CN101305004B/zh not_active Expired - Fee Related
- 2006-12-05 CA CA002632642A patent/CA2632642A1/en not_active Abandoned
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| NZ567048A (en) | 2010-12-24 |
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| CN101305004B (zh) | 2011-11-16 |
| JP2009518357A (ja) | 2009-05-07 |
| CN101305004A (zh) | 2008-11-12 |
| WO2007065892A1 (en) | 2007-06-14 |
| US8173658B2 (en) | 2012-05-08 |
| ATE473978T1 (de) | 2010-07-15 |
| DE602006015523D1 (de) | 2010-08-26 |
| EP2246352A1 (en) | 2010-11-03 |
| EP1963323B1 (en) | 2010-07-14 |
| DK1963323T3 (da) | 2010-10-25 |
| KR20080079250A (ko) | 2008-08-29 |
| EP1963323A1 (en) | 2008-09-03 |
| RU2008110911A (ru) | 2010-01-20 |
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