KR20080030666A - 헌팅턴병의 증상의 치료를 위한3,11b-시스-디하이드로테트라베나진의 용도 - Google Patents
헌팅턴병의 증상의 치료를 위한3,11b-시스-디하이드로테트라베나진의 용도 Download PDFInfo
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- KR20080030666A KR20080030666A KR1020087003481A KR20087003481A KR20080030666A KR 20080030666 A KR20080030666 A KR 20080030666A KR 1020087003481 A KR1020087003481 A KR 1020087003481A KR 20087003481 A KR20087003481 A KR 20087003481A KR 20080030666 A KR20080030666 A KR 20080030666A
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- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011824 transgenic rat model Methods 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
-
- 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
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0514501.6A GB0514501D0 (en) | 2005-07-14 | 2005-07-14 | Pharmaceutical compounds |
| GB0514501.6 | 2005-07-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080030666A true KR20080030666A (ko) | 2008-04-04 |
Family
ID=34897233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087003481A Withdrawn KR20080030666A (ko) | 2005-07-14 | 2006-07-13 | 헌팅턴병의 증상의 치료를 위한3,11b-시스-디하이드로테트라베나진의 용도 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20080319000A1 (https=) |
| EP (2) | EP1885363B1 (https=) |
| JP (1) | JP2009501202A (https=) |
| KR (1) | KR20080030666A (https=) |
| CN (1) | CN101282726A (https=) |
| AT (2) | ATE522215T1 (https=) |
| AU (1) | AU2006268098B2 (https=) |
| CA (1) | CA2615077A1 (https=) |
| CY (1) | CY1108653T1 (https=) |
| DE (1) | DE602006002982D1 (https=) |
| DK (1) | DK1885363T3 (https=) |
| ES (1) | ES2314931T3 (https=) |
| GB (1) | GB0514501D0 (https=) |
| HR (1) | HRP20080677T3 (https=) |
| ME (1) | ME01629B (https=) |
| NZ (1) | NZ565522A (https=) |
| PL (1) | PL1885363T3 (https=) |
| PT (1) | PT1885363E (https=) |
| RS (1) | RS50626B (https=) |
| RU (1) | RU2409365C2 (https=) |
| SI (1) | SI1885363T1 (https=) |
| WO (1) | WO2007007105A1 (https=) |
| ZA (1) | ZA200800905B (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2410947B (en) * | 2004-02-11 | 2008-09-17 | Cambridge Lab Ltd | Pharmaceutical compounds |
| GB0516168D0 (en) * | 2005-08-05 | 2005-09-14 | Cambridge Lab Ireland Ltd | Pharmaceutical compounds |
| EP2081929B1 (en) | 2006-11-08 | 2013-01-09 | Neurocrine Biosciences, Inc. | Substituted 3-isobutyl-9, 10-dimethoxy-1,3,4,6,7,11b-hexahydro-2h-pyrido[2,1-a]isoquinolin-2-ol compounds and methods relating thereto |
| GB0810857D0 (en) * | 2008-06-13 | 2008-07-23 | Cambridge Lab Ireland Ltd | Pharmaceutical compounds |
| WO2011019956A2 (en) * | 2009-08-12 | 2011-02-17 | Biovail Laboratories International (Barbados) S.R.L. | Pharmaceutical compositions |
| GB2462611A (en) * | 2008-08-12 | 2010-02-17 | Cambridge Lab | Pharmaceutical composition comprising tetrabenazine |
| US20110053866A1 (en) * | 2008-08-12 | 2011-03-03 | Biovail Laboratories International (Barbados) S.R.L. | Pharmaceutical compositions |
| US20120208773A1 (en) * | 2008-08-12 | 2012-08-16 | Valeant International (Barbados) Srl | Pharmaceutical compositions with tetrabenazine |
| GB2463452A (en) * | 2008-09-08 | 2010-03-17 | Cambridge Lab | Desmethyl derivatives of tetrabenazine and pharmaceutical compositions thereof |
| GB2463283A (en) * | 2008-09-08 | 2010-03-10 | Cambridge Lab | 3,11b-cis-dihydrotetrabenazine for use in treating asthma |
| GB2463451A (en) | 2008-09-08 | 2010-03-17 | Cambridge Lab | 3, 11b cis-dihydrotetrabenazine compounds for use in the treatment of dementia |
| EP3351247A1 (en) * | 2010-06-01 | 2018-07-25 | Auspex Pharmaceutical, Inc. | Benzoquinolone inhibitors of vmat2 |
| WO2012095548A2 (es) | 2011-01-13 | 2012-07-19 | Centro De Investigación Biomédica En Red De Enfermedades Neurodegenerativas (Ciberned) | Compuestos para el tratamiento de enfermedades neurodegenerativas |
| GB201705305D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705302D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705303D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| AU2018241940B2 (en) * | 2017-04-01 | 2023-09-28 | Adeptio Pharmaceuticals Limited | Dihydrotetrabenazine for use in the treatment a movement disorder |
| GB201705304D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| GB201705306D0 (en) | 2017-04-01 | 2017-05-17 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compositions |
| CA3097189A1 (en) | 2018-04-25 | 2019-10-31 | Shinkei Therapeutics Llc | Tetrabenazine transdermal delivery device |
| GB201808464D0 (en) | 2018-05-23 | 2018-07-11 | Adeptio Pharmaceuticals Ltd | Pharmaceutical compounds for use in treating huntington's disease |
| AU2020315331A1 (en) * | 2019-07-16 | 2022-02-03 | Rush University Medical Center | Use of a benzoate containing composition to treat neurodegenerative disorders |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3132147A (en) * | 1964-05-05 | |||
| US3159638A (en) * | 1964-12-01 | Xcha-chj | ||
| US3053845A (en) * | 1962-09-11 | Benzofykedocolines | ||
| US2830993A (en) * | 1958-04-15 | Quinolizine derivatives | ||
| US3009918A (en) * | 1961-11-21 | Chz ch | ||
| US3314966A (en) * | 1967-04-18 | Substituted benzo[a]quinolizines | ||
| US3095419A (en) * | 1963-06-25 | Process for preparing z-oxo-j- | ||
| US3123609A (en) * | 1964-03-03 | Benzo | ||
| US2954382A (en) * | 1960-09-27 | Xpreparation of hexahydrobenzoquinol- | ||
| US3209005A (en) * | 1965-09-28 | Hexahydro-llbh-benzo[a] quinolizines and processes therefor | ||
| US2843591A (en) * | 1958-07-15 | Method for preparing same | ||
| US3079395A (en) * | 1963-02-26 | Novel z-oxq-benzoquinoliaine | ||
| US3045021A (en) * | 1959-09-24 | 1962-07-17 | Hoffmann La Roche | Preparation of substituted 2-oxobenzoquinolizines |
| GB999092A (en) * | 1959-11-24 | 1965-07-21 | Wellcome Found | Method for making benzo(a)-quinolizine derivatives |
| US3375254A (en) * | 1961-09-29 | 1968-03-26 | Burroughs Wellcome Co | Manufacture of 1, 2, 3, 4, 6, 7-hexahydro-2-oxo-11bh-benzo(a)quinolizines |
| US3105079A (en) * | 1961-12-29 | 1963-09-24 | Pfizer & Co C | 10-aminobenzopyridocolines |
| US3390152A (en) * | 1965-10-21 | 1968-06-25 | Abbott Lab | 9, 10-alkoxy-3-alkyl-2, 2-(dithiosubstituted)-benzoquinolizines |
| JPS4836303B1 (https=) * | 1968-12-27 | 1973-11-02 | ||
| US3635986A (en) * | 1969-12-22 | 1972-01-18 | Miles Lab | 2-substituted amino-hexahydrobenzo(a)quinolizines |
| YU264675A (en) * | 1974-10-23 | 1982-05-31 | Chinoin Gyogyszer Es Vegyeszet | Process for obtaining benzo (a)-quinolizidine derivatives |
| GB1513824A (en) * | 1975-05-22 | 1978-06-14 | Wyeth John & Brother Ltd | 1,3,4,6,7,11b-hexahydro-2h-benzo(a)quinolizine derivative |
| US4133812A (en) * | 1975-11-21 | 1979-01-09 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | Process for producing benzo (a) quinolizine derivatives |
| US4304913A (en) * | 1978-11-20 | 1981-12-08 | Miles Laboratories, Inc. | Trans-2-substituted-amido-hexahydrobenzo [A]quinolizines |
| US4353656A (en) * | 1980-10-14 | 1982-10-12 | Xerox Corporation | Moving coil, multiple energy print hammer system including a closed loop servo |
| US4778054A (en) * | 1982-10-08 | 1988-10-18 | Glaxo Group Limited | Pack for administering medicaments to patients |
| AU591152B2 (en) * | 1985-07-30 | 1989-11-30 | Glaxo Group Limited | Devices for administering medicaments to patients |
| GB9004781D0 (en) * | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| US6087376A (en) * | 1997-02-05 | 2000-07-11 | University Of Kentucky Research Foundation | Use of lobeline compounds in the treatment of central nervous system diseases and pathologies |
| FR2794742B1 (fr) * | 1999-06-11 | 2005-06-03 | Sanofi Synthelabo | Nouveaux derives du benzene, un procede pour leur preparation et les compositions pharmaceutiques les contenant |
| US6632666B2 (en) * | 2000-01-14 | 2003-10-14 | Biolife Solutions, Inc. | Normothermic, hypothermic and cryopreservation maintenance and storage of cells, tissues and organs in gel-based media |
| MXPA02010222A (es) * | 2000-04-18 | 2003-05-23 | Agouron Pharma | Pirazoles para inhibir proteina cinasa. |
| EP1638529B1 (en) * | 2003-06-16 | 2016-08-10 | ANDRX Pharmaceuticals, LLC. | Oral extended-release composition |
| GB2410947B (en) * | 2004-02-11 | 2008-09-17 | Cambridge Lab Ltd | Pharmaceutical compounds |
| WO2006053067A2 (en) * | 2004-11-09 | 2006-05-18 | Prestwick Pharmaceuticals, Inc. | Combination of amantadine and a tetrabenazine compound for treating hyperkinetic disorders |
| KR100682506B1 (ko) * | 2005-01-18 | 2007-02-15 | (주)젠크로스 | 프라지콴텔, 또는 이의 염을 포함하는 약학 조성물 |
| GB0516168D0 (en) * | 2005-08-05 | 2005-09-14 | Cambridge Lab Ireland Ltd | Pharmaceutical compounds |
| GB2462611A (en) * | 2008-08-12 | 2010-02-17 | Cambridge Lab | Pharmaceutical composition comprising tetrabenazine |
| US20110053866A1 (en) * | 2008-08-12 | 2011-03-03 | Biovail Laboratories International (Barbados) S.R.L. | Pharmaceutical compositions |
| GB2463452A (en) * | 2008-09-08 | 2010-03-17 | Cambridge Lab | Desmethyl derivatives of tetrabenazine and pharmaceutical compositions thereof |
| GB2463451A (en) * | 2008-09-08 | 2010-03-17 | Cambridge Lab | 3, 11b cis-dihydrotetrabenazine compounds for use in the treatment of dementia |
| GB2463283A (en) * | 2008-09-08 | 2010-03-10 | Cambridge Lab | 3,11b-cis-dihydrotetrabenazine for use in treating asthma |
-
2005
- 2005-07-14 GB GBGB0514501.6A patent/GB0514501D0/en not_active Ceased
-
2006
- 2006-05-31 ME MEP-2008-916A patent/ME01629B/me unknown
- 2006-07-13 EP EP06764942A patent/EP1885363B1/en active Active
- 2006-07-13 AT AT08017191T patent/ATE522215T1/de not_active IP Right Cessation
- 2006-07-13 EP EP08017191A patent/EP2027861B1/en active Active
- 2006-07-13 ZA ZA200800905A patent/ZA200800905B/xx unknown
- 2006-07-13 ES ES06764942T patent/ES2314931T3/es active Active
- 2006-07-13 CA CA002615077A patent/CA2615077A1/en not_active Abandoned
- 2006-07-13 RU RU2008105590/15A patent/RU2409365C2/ru not_active IP Right Cessation
- 2006-07-13 PT PT06764942T patent/PT1885363E/pt unknown
- 2006-07-13 CN CNA2006800339758A patent/CN101282726A/zh active Pending
- 2006-07-13 US US11/995,436 patent/US20080319000A1/en not_active Abandoned
- 2006-07-13 WO PCT/GB2006/002593 patent/WO2007007105A1/en not_active Ceased
- 2006-07-13 NZ NZ565522A patent/NZ565522A/en not_active IP Right Cessation
- 2006-07-13 SI SI200630147T patent/SI1885363T1/sl unknown
- 2006-07-13 AU AU2006268098A patent/AU2006268098B2/en not_active Ceased
- 2006-07-13 AT AT06764942T patent/ATE409481T1/de active
- 2006-07-13 PL PL06764942T patent/PL1885363T3/pl unknown
- 2006-07-13 DK DK06764942T patent/DK1885363T3/da active
- 2006-07-13 DE DE602006002982T patent/DE602006002982D1/de active Active
- 2006-07-13 KR KR1020087003481A patent/KR20080030666A/ko not_active Withdrawn
- 2006-07-13 HR HR20080677T patent/HRP20080677T3/xx unknown
- 2006-07-13 JP JP2008520952A patent/JP2009501202A/ja active Pending
- 2006-07-13 RS RSP-2008/0492A patent/RS50626B/sr unknown
-
2008
- 2008-12-22 CY CY20081101475T patent/CY1108653T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ565522A (en) | 2010-04-30 |
| RS50626B (sr) | 2010-06-30 |
| PT1885363E (pt) | 2009-01-08 |
| DK1885363T3 (da) | 2008-12-08 |
| EP2027861B1 (en) | 2011-08-31 |
| DE602006002982D1 (de) | 2008-11-13 |
| EP2027861A1 (en) | 2009-02-25 |
| CA2615077A1 (en) | 2007-01-18 |
| RU2008105590A (ru) | 2009-08-20 |
| JP2009501202A (ja) | 2009-01-15 |
| CY1108653T1 (el) | 2014-04-09 |
| ATE409481T1 (de) | 2008-10-15 |
| US20080319000A1 (en) | 2008-12-25 |
| ME01629B (me) | 2010-06-30 |
| CN101282726A (zh) | 2008-10-08 |
| ZA200800905B (en) | 2010-04-28 |
| AU2006268098A1 (en) | 2007-01-18 |
| SI1885363T1 (sl) | 2009-02-28 |
| AU2006268098B2 (en) | 2011-02-17 |
| ES2314931T3 (es) | 2009-03-16 |
| HK1111085A1 (en) | 2008-08-01 |
| WO2007007105A1 (en) | 2007-01-18 |
| ATE522215T1 (de) | 2011-09-15 |
| PL1885363T3 (pl) | 2009-05-29 |
| HRP20080677T3 (hr) | 2009-02-28 |
| RU2409365C2 (ru) | 2011-01-20 |
| GB0514501D0 (en) | 2005-08-24 |
| EP1885363B1 (en) | 2008-10-01 |
| EP1885363A1 (en) | 2008-02-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20080213 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |