JP2012533601A - 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 - Google Patents
運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 Download PDFInfo
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- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- RLTPJVKHGBFGQA-UHFFFAOYSA-N thiadiazolidine Chemical compound C1CSNN1 RLTPJVKHGBFGQA-UHFFFAOYSA-N 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22795109P | 2009-07-23 | 2009-07-23 | |
| US61/227,951 | 2009-07-23 | ||
| PCT/EP2010/060571 WO2011009890A2 (en) | 2009-07-23 | 2010-07-21 | Use of azabicycloalkyl derivatives or pyrrolidine-2-one derivatives |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2015117200A Division JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012533601A true JP2012533601A (ja) | 2012-12-27 |
| JP2012533601A5 JP2012533601A5 (OSRAM) | 2015-07-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012521032A Pending JP2012533601A (ja) | 2009-07-23 | 2010-07-21 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
| JP2015117200A Pending JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015117200A Pending JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20120157464A1 (OSRAM) |
| EP (2) | EP2959902A1 (OSRAM) |
| JP (2) | JP2012533601A (OSRAM) |
| CN (1) | CN102573842A (OSRAM) |
| WO (1) | WO2011009890A2 (OSRAM) |
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| JPS6262265A (ja) * | 1985-09-13 | 1987-03-18 | Hitachi Ltd | 復水器自動検査補修システム |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| CA2830458A1 (en) * | 2011-03-18 | 2012-09-27 | Novartis Ag | Combinations of alpha 7 nicotinic acetylcholine receptor activators and mglur5 antagonists for use in dopamine induced dyskinesia in parkinson's disease |
| WO2013010679A1 (en) | 2011-07-15 | 2013-01-24 | Novartis Ag | Salts of aza-bicyclic di-aryl ethers and methods to make them or their precursors |
| JOP20130273B1 (ar) | 2012-09-11 | 2021-08-17 | Genzyme Corp | مثبطات انزيم (سينثاز) غلوكوسيل سيراميد |
| BR112015016994A8 (pt) * | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
| US20150313884A1 (en) | 2013-01-15 | 2015-11-05 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| WO2014111837A1 (en) * | 2013-01-15 | 2014-07-24 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| PL3027600T3 (pl) * | 2013-07-31 | 2022-08-08 | Novartis Ag | 1,4-dwupodstawione pochodne pirydazyny i ich zastosowanie do leczenia stanów związanych z niedoborem smn |
| IL295255A (en) | 2020-02-03 | 2022-10-01 | Genzyme Corp | Methods for treating neurological symptoms associated with lysosomal storage diseases |
| MX2023001014A (es) | 2020-07-24 | 2023-03-01 | Genzyme Corp | Composiciones farmaceuticas que comprenden venglustat. |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001085727A1 (en) * | 2000-05-05 | 2001-11-15 | Novartis Ag | Azabicyclic carbamates and their use as alpha-7 nicotinic acetylcholine receptor agonists |
| WO2004016608A1 (en) * | 2002-08-14 | 2004-02-26 | Neurosearch A/S | Novel quinuclidine derivatives and their use |
| WO2004022556A1 (en) * | 2002-09-04 | 2004-03-18 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nachr agonist |
| US20040229868A1 (en) * | 2002-08-30 | 2004-11-18 | Memory Pharmaceuticals Corp. | Heterocyclic compounds, methods for the preparation thereof, and uses thereof |
| WO2005118535A1 (en) * | 2004-05-28 | 2005-12-15 | Novartis Ag | Substituted pyrrolidine-2-ones |
| WO2005123732A1 (en) * | 2004-06-18 | 2005-12-29 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| WO2006005608A1 (en) * | 2004-07-14 | 2006-01-19 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha.7-nachr ligands for the treatment of cns diseases |
| US20070060588A1 (en) * | 2003-12-22 | 2007-03-15 | Jianguo Ji | Fused bicycloheterocycle substituted quinuclidine derivatives |
| WO2007045478A1 (en) * | 2005-10-21 | 2007-04-26 | Novartis Ag | Novel 1-aza bicycloalkyl derivatives for the treatment of psychotic and neurodegenerative disorders |
| WO2007068476A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | [ (1h- indol- 5 -yl) -heteroaryloxy] - (1-aza-bicyclo [3.3.1] nonanes as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenrative disorders. |
| WO2007068475A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | (1-aza-bicyclo[3.3.1] n0n-4-yl)-[5-(ih-indol-5-yl)-heteroaryl]-amines as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenerative disorders |
| WO2008087529A1 (en) * | 2007-01-16 | 2008-07-24 | Siena Biotech S.P.A. | Nicotinic acetylcholine receptor modulators |
| WO2009043780A1 (en) * | 2007-10-04 | 2009-04-09 | F. Hoffmann-La Roche Ag | Tetrazole-substituted aryl amide derivatives and uses thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0128996D0 (en) | 2001-12-04 | 2002-01-23 | Novartis Ag | Organic compounds |
| SE0201943D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New use |
| BR0203527A (pt) | 2002-09-03 | 2004-05-25 | Kluber Lubrication Lubrificant | Fluìdo transmissor de calor e seu respectivo processo de obtenção |
| CA2549965A1 (en) | 2003-10-31 | 2005-05-19 | Astrazeneca Ab | Alkynes iii |
| WO2005044267A1 (en) | 2003-10-31 | 2005-05-19 | Astrazeneca Ab | Alkynes ii |
| CA2549967A1 (en) | 2003-10-31 | 2005-05-19 | Astrazeneca Ab | Alkynes i |
| US7071143B2 (en) | 2004-01-28 | 2006-07-04 | Eastman Kodak Company | Direct thermographic materials with improved protective layers |
| ATE441792T1 (de) | 2005-04-25 | 2009-09-15 | Hoerbiger & Co | Betätigungssteuereinrichtung für die lamellen einer hydraulischen doppelkupplung |
| AU2006329007A1 (en) | 2005-12-20 | 2007-06-28 | Novartis Ag | Nicotinic acid derivatives as modulators of metabotropic glutamate receptors |
| WO2007085036A1 (en) | 2006-01-26 | 2007-08-02 | Medizinische Universität Wien | Treatment of friedreich' s ataxia |
| AU2007219009B2 (en) | 2006-02-22 | 2012-12-20 | Apotex Technologies Inc. | The use of deferiprone and methods to treat and/or prevent Friedreich Ataxia resulting from intracellular mishandling of iron |
| JP2011516489A (ja) * | 2008-03-31 | 2011-05-26 | ユニバーシティ・オブ・サウス・フロリダ | 疾患誘発性運動失調症および非運動失調性平衡異常の治療法 |
-
2010
- 2010-07-21 WO PCT/EP2010/060571 patent/WO2011009890A2/en not_active Ceased
- 2010-07-21 JP JP2012521032A patent/JP2012533601A/ja active Pending
- 2010-07-21 EP EP15176482.6A patent/EP2959902A1/en not_active Withdrawn
- 2010-07-21 EP EP10734744A patent/EP2456438A2/en not_active Ceased
- 2010-07-21 CN CN2010800335791A patent/CN102573842A/zh active Pending
- 2010-07-21 US US13/383,690 patent/US20120157464A1/en not_active Abandoned
-
2015
- 2015-06-10 JP JP2015117200A patent/JP2015212277A/ja active Pending
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001085727A1 (en) * | 2000-05-05 | 2001-11-15 | Novartis Ag | Azabicyclic carbamates and their use as alpha-7 nicotinic acetylcholine receptor agonists |
| WO2004016608A1 (en) * | 2002-08-14 | 2004-02-26 | Neurosearch A/S | Novel quinuclidine derivatives and their use |
| US20040229868A1 (en) * | 2002-08-30 | 2004-11-18 | Memory Pharmaceuticals Corp. | Heterocyclic compounds, methods for the preparation thereof, and uses thereof |
| WO2004022556A1 (en) * | 2002-09-04 | 2004-03-18 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nachr agonist |
| US20070060588A1 (en) * | 2003-12-22 | 2007-03-15 | Jianguo Ji | Fused bicycloheterocycle substituted quinuclidine derivatives |
| WO2005118535A1 (en) * | 2004-05-28 | 2005-12-15 | Novartis Ag | Substituted pyrrolidine-2-ones |
| WO2005123732A1 (en) * | 2004-06-18 | 2005-12-29 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| WO2006005608A1 (en) * | 2004-07-14 | 2006-01-19 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha.7-nachr ligands for the treatment of cns diseases |
| WO2007045478A1 (en) * | 2005-10-21 | 2007-04-26 | Novartis Ag | Novel 1-aza bicycloalkyl derivatives for the treatment of psychotic and neurodegenerative disorders |
| WO2007068476A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | [ (1h- indol- 5 -yl) -heteroaryloxy] - (1-aza-bicyclo [3.3.1] nonanes as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenrative disorders. |
| WO2007068475A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | (1-aza-bicyclo[3.3.1] n0n-4-yl)-[5-(ih-indol-5-yl)-heteroaryl]-amines as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenerative disorders |
| WO2008087529A1 (en) * | 2007-01-16 | 2008-07-24 | Siena Biotech S.P.A. | Nicotinic acetylcholine receptor modulators |
| WO2009043780A1 (en) * | 2007-10-04 | 2009-04-09 | F. Hoffmann-La Roche Ag | Tetrazole-substituted aryl amide derivatives and uses thereof |
Non-Patent Citations (2)
| Title |
|---|
| JPN5012015516; ＺＥＳＩＥＷＩＣＺ ＴＨＥＲＥＳＡ Ａ: 'ＳＵＢＪＥＣＴＩＶＥ ＩＭＰＲＯＶＥＭＥＮＴ ＩＮ ＰＲＯＰＲＩＯＣＥＰＴＩＯＮ ＩＮ ２ ＰＡＴＩＥＮＴＳ 以下備考' ＪＯＵＲＮＡＬ ＯＦ ＣＬＩＮＩＣＡＬ ＮＥＵＲＯＭＵＳＣＵＬＡＲ ＤＩＳＥＡＳＥ Ｖ１０ Ｎ４, 200906, Ｐ１９１-１９３ * |
| JPN6014034250; Ｄｏｍｉｎｉｋ Ｆｅｕｅｒｂａｃｈ ｅｔ ａｌ: Ｎｅｕｒｏｐｈａｒｍａｃｏｌｏｇｙ ５６, 2009, ２５４-２６３ * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015212277A (ja) | 2015-11-26 |
| CN102573842A (zh) | 2012-07-11 |
| US20120157464A1 (en) | 2012-06-21 |
| WO2011009890A3 (en) | 2011-09-29 |
| EP2959902A1 (en) | 2015-12-30 |
| WO2011009890A2 (en) | 2011-01-27 |
| EP2456438A2 (en) | 2012-05-30 |
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