SG192078A1 - Pyrrole derivatives used as modulators of alpha7 nachr - Google Patents
Pyrrole derivatives used as modulators of alpha7 nachr Download PDFInfo
- Publication number
- SG192078A1 SG192078A1 SG2013055769A SG2013055769A SG192078A1 SG 192078 A1 SG192078 A1 SG 192078A1 SG 2013055769 A SG2013055769 A SG 2013055769A SG 2013055769 A SG2013055769 A SG 2013055769A SG 192078 A1 SG192078 A1 SG 192078A1
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- Singapore
- Prior art keywords
- alkyl
- optionally substituted
- methyl
- pyrrol
- propionyl
- Prior art date
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- 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
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- 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
- A61P25/34—Tobacco-abuse
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Toxicology (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN151KO2011 | 2011-02-03 | ||
| PCT/IB2012/050442 WO2012104782A1 (en) | 2011-02-03 | 2012-01-31 | Pyrrole derivatives used as modulators of alpha7 nachr |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SG192078A1 true SG192078A1 (en) | 2013-08-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG2013055769A SG192078A1 (en) | 2011-02-03 | 2012-01-31 | Pyrrole derivatives used as modulators of alpha7 nachr |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20130310419A1 (enExample) |
| EP (1) | EP2670744B1 (enExample) |
| JP (1) | JP5865397B2 (enExample) |
| KR (1) | KR20140041442A (enExample) |
| CN (1) | CN103443092B (enExample) |
| AU (1) | AU2012213086B2 (enExample) |
| BR (1) | BR112013019893A2 (enExample) |
| CA (1) | CA2825519A1 (enExample) |
| MX (1) | MX344701B (enExample) |
| SG (1) | SG192078A1 (enExample) |
| WO (1) | WO2012104782A1 (enExample) |
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| KR20140026378A (ko) | 2011-02-23 | 2014-03-05 | 루핀 리미티드 | 알파 7 ｎａｃｈｒ 조절자로서 헤테로아릴 유도체 |
| SG193387A1 (en) * | 2011-03-31 | 2013-10-30 | Lupin Ltd | Pyrrole derivatives as nicotinic acetylcholine receptor modulators for use in the treatment of neurodegenerative disorders such as alzheimer's and parkinson's disease |
| WO2013132380A1 (en) | 2012-03-06 | 2013-09-12 | Lupin Limited | Thiazole derivatives as alpha 7 nachr modulators |
| EP2945936A1 (en) | 2012-11-12 | 2015-11-25 | Lupin Limited | Thiazole derivatives as alpha 7 nachr modulators |
| US9617211B2 (en) | 2013-01-16 | 2017-04-11 | Lupin Limited | Pyrrole derivatives as alpha 7 nAChR modulators |
| AU2014229300A1 (en) * | 2013-03-13 | 2015-06-11 | Lupin Limited | Pyrrole derivatives as alpha 7 nAChR modulators |
| TW201446243A (zh) | 2013-06-03 | 2014-12-16 | Lupin Ltd | 4-(5-(4-氯苯基)-2-(2-環丙基乙醯基)-1,4-二甲基-1氫-吡咯-3-基)苯磺醯胺作為α7尼古丁乙醯膽鹼受體調節劑 |
| WO2014203150A1 (en) | 2013-06-17 | 2014-12-24 | Lupin Limited | Pyrrole derivatives as alpha 7 nachr modulators |
| GB2516045A (en) * | 2013-07-09 | 2015-01-14 | Neuro Bio Ltd | Neurodegenerative disorders |
| DK3204357T3 (da) * | 2014-10-10 | 2022-04-04 | High Force Res Limited | Fluorescerende, syntetiske retinoider |
| EP3623371A1 (en) | 2014-12-16 | 2020-03-18 | Axovant Sciences GmbH | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| CA2988968A1 (en) | 2015-06-10 | 2016-12-15 | Forum Pharmaceuticals, Inc. | Aminobenzisoxazole compounds as agonists of a7-nicotinic acetylcholine receptors |
| JP2018523707A (ja) | 2015-08-12 | 2018-08-23 | アクソバント サイエンシズ ゲーエムベーハー | α７−ニコチン性アセチルコリン受容体のアゴニストとしてのジェミナル置換アミノベンゾイソオキサゾール化合物 |
| WO2017170934A1 (ja) * | 2016-04-01 | 2017-10-05 | 国立大学法人 東京大学 | 新規化合物とその合成方法 |
| HU231414B1 (hu) | 2018-07-13 | 2023-08-28 | Richter Gedeon Nyrt. | Tiadiazin származékok |
Family Cites Families (31)
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| US4808597A (en) | 1983-07-05 | 1989-02-28 | Pfizer Inc. | Method for inhibiting the degradation of cartilage |
| AU626881B2 (en) | 1988-07-14 | 1992-08-13 | F. Hoffmann-La Roche Ag | Benzofused heterocyclics used as pharmaceuticals |
| US5756529A (en) * | 1995-09-29 | 1998-05-26 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides for use in veterinary therapies |
| JPH11180871A (ja) * | 1997-09-26 | 1999-07-06 | Sankyo Co Ltd | １，２−ジフェニルピロール誘導体を含有する医薬 |
| US6313107B1 (en) | 2000-08-29 | 2001-11-06 | Allergan Sales, Inc. | Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI |
| OA13315A (en) | 2003-10-14 | 2007-04-13 | Intermune Inc | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of HCV replication. |
| WO2005092843A1 (en) | 2004-03-29 | 2005-10-06 | Neurosearch A/S | Novel urea derivatives and their medical use |
| US20060142349A1 (en) | 2004-12-23 | 2006-06-29 | Pfizer Inc | Methods of modulating the activities of alpha-7 nicotinic acetylcholine receptor |
| US7750011B2 (en) | 2005-02-15 | 2010-07-06 | Neurosearch A/S | Diazabicyclic aryl derivatives and their medical use |
| JP2006316054A (ja) * | 2005-04-15 | 2006-11-24 | Tanabe Seiyaku Co Ltd | 高コンダクタンス型カルシウム感受性ｋチャネル開口薬 |
| NZ566036A (en) | 2005-09-13 | 2010-06-25 | Janssen Pharmaceutica Nv | 2-Aniline-4-aryl substituted thiazole derivatives that modulate the alpha7 nicotinic receptor |
| JP2009526814A (ja) | 2006-02-16 | 2009-07-23 | ノイロサーチ アクティーゼルスカブ | 鏡像異性的に純粋なキヌクリジニルオキシピリダジン、及びニコチン性アセチルコリン受容体リガンドとしてのその使用 |
| CN101384549B (zh) * | 2006-02-20 | 2011-04-13 | 安斯泰来制药株式会社 | 吡咯衍生物或其盐 |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| BRPI0712667A2 (pt) | 2006-06-27 | 2012-09-04 | Abbott Lab | derivados do pirrol e seus métodos de uso |
| WO2008002956A2 (en) | 2006-06-27 | 2008-01-03 | Abbott Laboratories | Thiazoline and oxazoline derivatives and their methods of use |
| JPWO2008156094A1 (ja) | 2007-06-19 | 2010-08-26 | 杏林製薬株式会社 | ピリダジノン誘導体及びそれらを有効成分とするｐｄｅ阻害剤 |
| MX2010001135A (es) | 2007-08-08 | 2010-03-09 | Neurosearch As | Nuevos derivados de 1,2,3-triazol, utiles como modulares de receptores de acetilcolina nicotinicos. |
| KR101186704B1 (ko) | 2007-10-04 | 2012-09-27 | 에프. 호프만-라 로슈 아게 | 테트라졸-치환된 아릴 아마이드 유도체 및 이의 용도 |
| WO2009043784A1 (en) | 2007-10-04 | 2009-04-09 | F. Hoffmann-La Roche Ag | Cyclopropyl aryl amide derivatives and uses thereof |
| JO2784B1 (en) | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| MY152486A (en) | 2008-03-19 | 2014-10-15 | Janssen Pharmaceutica Nv | Trisubstituted 1,2,4 - triazoles as nicotinic acetylcholine receptor modulators |
| US7786171B2 (en) | 2008-04-04 | 2010-08-31 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
| UY31769A1 (es) | 2008-04-17 | 2009-09-30 | Derivados del indol con actividad modulatoria del receptor nicotínico de acetilcolina | |
| US8779158B2 (en) | 2008-05-09 | 2014-07-15 | Janssen Pharmaceutica Nv | Trisubstituted pyrazoles as acetylcholine receptor modulators |
| WO2010013794A1 (en) | 2008-07-28 | 2010-02-04 | Eisai R&D Management Co., Ltd. | Spiroaminodihydrothiazine derivatives |
| CN102164899B (zh) | 2008-09-25 | 2014-11-26 | 霍夫曼-拉罗奇有限公司 | 用作抗异常脂肪血症及相关疾病的fxr调节剂的取代的吲唑或四氢吲唑类 |
| US8563579B2 (en) | 2009-01-15 | 2013-10-22 | Anvyl Llc | α-7 nicotinic acetylcholine receptor allosteric modulators, their derivatives and uses thereof |
| US20120071469A1 (en) | 2009-05-14 | 2012-03-22 | Neurosearch A/S | Novel 1,4-diaza-bicyclo[3.2.1]octane derivatives useful as nicotinic acetylcholine receptor modulators |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| JO3078B1 (ar) | 2009-11-27 | 2017-03-15 | Janssen Pharmaceutica Nv | مورفولينوثيازولات بصفتها منظمات الوستيرية نوع الفا 7 موجبة |
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2012
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- 2012-01-31 AU AU2012213086A patent/AU2012213086B2/en not_active Ceased
- 2012-01-31 WO PCT/IB2012/050442 patent/WO2012104782A1/en not_active Ceased
- 2012-01-31 CA CA2825519A patent/CA2825519A1/en not_active Abandoned
- 2012-01-31 KR KR1020137022397A patent/KR20140041442A/ko not_active Ceased
- 2012-01-31 EP EP12706923.5A patent/EP2670744B1/en not_active Not-in-force
- 2012-01-31 CN CN201280013694.1A patent/CN103443092B/zh not_active Expired - Fee Related
- 2012-01-31 JP JP2013552304A patent/JP5865397B2/ja not_active Expired - Fee Related
- 2012-01-31 SG SG2013055769A patent/SG192078A1/en unknown
- 2012-01-31 BR BR112013019893A patent/BR112013019893A2/pt not_active IP Right Cessation
- 2012-01-31 US US13/983,362 patent/US20130310419A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NZ613467A (en) | 2015-03-27 |
| EP2670744B1 (en) | 2015-05-27 |
| KR20140041442A (ko) | 2014-04-04 |
| EP2670744A1 (en) | 2013-12-11 |
| JP2014504632A (ja) | 2014-02-24 |
| US20130310419A1 (en) | 2013-11-21 |
| CN103443092B (zh) | 2015-11-25 |
| JP5865397B2 (ja) | 2016-02-17 |
| MX344701B (es) | 2017-01-03 |
| AU2012213086A1 (en) | 2013-08-22 |
| BR112013019893A2 (pt) | 2016-10-11 |
| CN103443092A (zh) | 2013-12-11 |
| WO2012104782A1 (en) | 2012-08-09 |
| AU2012213086B2 (en) | 2016-05-05 |
| MX2013008947A (es) | 2014-01-08 |
| CA2825519A1 (en) | 2012-09-08 |
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