NZ580856A - N-oxide and/or di-n-oxide derivatives of dopamine receptor stabilizers/modulators displaying improved cardiovascular side-effects profiles - Google Patents
N-oxide and/or di-n-oxide derivatives of dopamine receptor stabilizers/modulators displaying improved cardiovascular side-effects profilesInfo
- Publication number
- NZ580856A NZ580856A NZ580856A NZ58085608A NZ580856A NZ 580856 A NZ580856 A NZ 580856A NZ 580856 A NZ580856 A NZ 580856A NZ 58085608 A NZ58085608 A NZ 58085608A NZ 580856 A NZ580856 A NZ 580856A
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| SE0700893 | 2007-04-12 | ||
| PCT/SE2008/050414 WO2008127188A1 (en) | 2007-04-12 | 2008-04-11 | N-oxide and/or di-n-oxide derivatives of dopamine receptor stabilizers/modulators displaying improved cardiovascular side-effects profiles |
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| WO2010058019A1 (en) | 2008-11-24 | 2010-05-27 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | 3-phenyl-3-methoxypyrrolidine derivatives as modulators of cortical catecholaminergic neurotransmission |
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| EP2611759A1 (en) | 2010-09-03 | 2013-07-10 | Ivax International Gmbh | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| US9018202B2 (en) * | 2010-12-03 | 2015-04-28 | Allergan, Inc. | Methods for treating diseases of the retina |
| CA2847736A1 (en) | 2011-09-07 | 2013-03-14 | IVAX International GmbH | A new polymorphic form of pridopidine hydrochloride |
| TWI579272B (zh) | 2011-12-08 | 2017-04-21 | 梯瓦製藥國際有限責任公司 | 普多比啶（ｐｒｉｄｏｐｉｄｉｎｅ）之氫溴酸鹽 |
| JP6177875B2 (ja) | 2012-04-04 | 2017-08-09 | テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハーＴｅｖａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | 併用療法のための医薬組成物 |
| SG11201509729YA (en) | 2013-06-21 | 2015-12-30 | Teva Pharmaceuticals Int Gmbh | Use of high dose pridopidine for treating huntington's disease |
| US11090297B2 (en) | 2013-06-21 | 2021-08-17 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating huntington's disease |
| TW201613859A (en) | 2014-06-30 | 2016-04-16 | Teva Pharma | Analogs of PRIDOPIDINE, their preparation and use |
| CA2970799A1 (en) | 2014-12-22 | 2016-06-30 | Teva Pharmaceuticals International Gmbh | L-tartrate salt of pridopidine |
| US11471449B2 (en) | 2015-02-25 | 2022-10-18 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine to improve cognitive function and for treating Alzheimer's disease |
| MX378579B (es) | 2015-02-25 | 2025-03-11 | Prilenia Neurotherapeutics Ltd | Uso de pridopidina para mejorar la funcion cognitiva y para tratamiento de enfermedad de alzheimer. |
| AR105434A1 (es) | 2015-07-22 | 2017-10-04 | Teva Pharmaceuticals Int Gmbh | Proceso para preparar pridopidina |
| DK3419622T3 (da) | 2016-02-24 | 2024-06-03 | Prilenia Neurotherapeutics Ltd | Behandling af neurodegenerativ øjensygdom med pridopidin |
| EP4516356A3 (en) | 2016-08-24 | 2025-05-14 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine for treating functional decline |
| MX2019002190A (es) | 2016-08-24 | 2019-09-11 | Prilenia Therapeutics Dev Ltd | Uso de pridopidina para tratar distonías. |
| US12102627B2 (en) | 2016-09-16 | 2024-10-01 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine for treating rett syndrome |
| PL3570940T3 (pl) | 2017-01-20 | 2024-06-17 | Prilenia Neurotherapeutics Ltd. | Pridopidyna do zastosowania w leczeniu zespołu łamliwego chromosomu x |
| EP4620471A3 (en) | 2017-08-14 | 2025-11-26 | Prilenia Neurotherapeutics Ltd. | Treating amyotrophic lateral sclerosis with pridopidine |
| EA202090542A1 (ru) | 2017-08-30 | 2020-06-08 | Приления Ньюротерапьютикс Лтд. | Высококонцентрированные лекарственные формы придопидина |
| EP3678664A1 (en) | 2017-09-08 | 2020-07-15 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| US12036213B2 (en) | 2017-09-08 | 2024-07-16 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| WO2020161707A1 (en) | 2019-02-04 | 2020-08-13 | Prilenia Neurotherapeutics Ltd. | Low dose pridopidine for parkinson's disease and other diseases associated with parkinsonism |
| CN116472043A (zh) * | 2020-10-20 | 2023-07-21 | 普瑞尼亚神经治疗有限公司 | 普利多匹定和类似物用于治疗焦虑和抑郁的用途 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1217296A (en) | 1917-01-11 | 1917-02-27 | Lewis A Peckham | Shock-absorber. |
| US2813097A (en) | 1955-08-16 | 1957-11-12 | Upjohn Co | 3-hydroxy-n-methylmorphinan-n-oxide |
| US2813098A (en) | 1955-08-16 | 1957-11-12 | Upjohn Co | 3-methoxy-n-methylmorphinan n-oxide |
| US3131185A (en) | 1959-03-18 | 1964-04-28 | Orsymonde | Nicotinic esters of hydroxyl derivatives of the phenanthrenic alkaloids of opium, and process for the preparation of these esters |
| BE638369A (enExample) | 1962-10-10 | |||
| CH481124A (de) | 1966-09-21 | 1969-11-15 | Geigy Ag J R | Verfahren zur Herstellung von neuen, kondensierten heterocyclischen Verbindungen |
| CA2071897A1 (en) | 1989-12-28 | 1991-06-29 | Richard A. Glennon | Sigma receptor ligands and the use thereof |
| DK0641320T3 (da) * | 1991-04-17 | 2001-08-20 | Upjohn Co | Substituerede (S)-3-phenylpiperidinderivater, deres fremstilling og deres anvendelse som dopaminautoreceptorantagonister |
| PT100639A (pt) | 1991-06-27 | 1993-09-30 | Univ Virginia Commonwealth | Metodo para o tratamento terapeutico com compostos que sao ligandos ao receptor sigma e compostos ai utilizados, nomeadamente derivados fenilalquil-amina, aminotetralina,piperazina e piperidina |
| IL112099A (en) * | 1993-12-23 | 1999-07-14 | Ortho Pharma Corp | N-oxides of 4-arylpiperazines and 4-arylpiperidines and pharmaceutical compositions containing them |
| CA2144669A1 (en) | 1994-03-29 | 1995-09-30 | Kozo Akasaka | Biphenyl derivatives |
| AU757870B2 (en) * | 1998-11-23 | 2003-03-06 | Sepracor, Inc. | Pharmaceutical compositions containing olanzapine-N-oxide |
| SE9904723D0 (sv) * | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
| SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
| SE0200301D0 (sv) * | 2002-02-01 | 2002-02-01 | Axon Biochemicals Bv | Thio-carbostyril derivative |
| KR101245075B1 (ko) | 2004-06-08 | 2013-03-18 | 엔에스아베 필리알 아프 뉴로서치 스웨덴 아베 스베리게 | 도파민 신경전달의 모듈레이터로서 신 2기치환된페닐피페리딘/피페라진 |
| EP2204363A1 (en) | 2004-06-08 | 2010-07-07 | NSAB, Filial af NeuroSearch Sweden AB, Sverige | New disubstituted phenylpiperidines/piperazines as modulators of dopamine neurotransmission |
| SG169238A1 (en) * | 2004-08-11 | 2011-03-30 | Williamsburg Holdings Llc | Noncardiotoxic pharmaceutical compounds |
| WO2006040155A1 (en) | 2004-10-13 | 2006-04-20 | Neurosearch Sweden Ab | Process for the synthesis of 4-(3-methanesulfonylphenyl)-1-n-propyl-piperidine |
| WO2007023141A1 (en) * | 2005-08-22 | 2007-03-01 | Solvay Pharmaceuticals B.V. | N-oxides as prodrugs of piperazine & piperidine derivatives |
| SE529246C2 (sv) | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
| EP2024363B1 (en) * | 2006-05-02 | 2012-08-01 | Abbott Healthcare Products B.V. | N-oxides of pyridylmethylpiperazine and -piperidine derivatives |
| WO2011107583A1 (en) * | 2010-03-04 | 2011-09-09 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Substituted 4-phenyl-n-alkyl-piperidines for preventing onset or slowing progression of neurodegenerative disorders |
| US20130203886A1 (en) * | 2010-03-05 | 2013-08-08 | Nileshkumar Prakash Kukalyekar | Process for the production of an uhmwpe article |
| EP2611759A1 (en) | 2010-09-03 | 2013-07-10 | Ivax International Gmbh | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| CA2847736A1 (en) | 2011-09-07 | 2013-03-14 | IVAX International GmbH | A new polymorphic form of pridopidine hydrochloride |
| TWI579272B (zh) | 2011-12-08 | 2017-04-21 | 梯瓦製藥國際有限責任公司 | 普多比啶（ｐｒｉｄｏｐｉｄｉｎｅ）之氫溴酸鹽 |
| JP6177875B2 (ja) | 2012-04-04 | 2017-08-09 | テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハーＴｅｖａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ | 併用療法のための医薬組成物 |
| IN2015DN03219A (enExample) | 2012-09-27 | 2015-10-02 | Teva Pharma | |
| WO2014052935A2 (en) | 2012-09-27 | 2014-04-03 | Teva Pharmaceutical Industries Ltd. | Combination of rasagiline and pridopidine for treating neurodegenerative disorders, in particular huntington's disease |
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2008
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| AU2008239841B2 (en) | 2013-07-18 |
| JP2010523651A (ja) | 2010-07-15 |
| WO2008127188A1 (en) | 2008-10-23 |
| CY1115337T1 (el) | 2017-01-04 |
| CA2683719C (en) | 2015-07-14 |
| IL201401A (en) | 2015-10-29 |
| JP5393654B2 (ja) | 2014-01-22 |
| CN101711236A (zh) | 2010-05-19 |
| EP2146961B1 (en) | 2014-01-29 |
| PL2146961T3 (pl) | 2014-09-30 |
| US9139525B2 (en) | 2015-09-22 |
| MX2009011020A (es) | 2009-10-30 |
| RU2470013C2 (ru) | 2012-12-20 |
| EP2146961A4 (en) | 2011-08-03 |
| SI2146961T1 (sl) | 2014-08-29 |
| IL201401A0 (en) | 2010-05-31 |
| CN101711236B (zh) | 2012-10-31 |
| BRPI0810161A2 (pt) | 2014-12-30 |
| AU2008239841A1 (en) | 2008-10-23 |
| PT2146961E (pt) | 2014-04-30 |
| HRP20140380T1 (hr) | 2014-08-15 |
| DK2146961T3 (da) | 2014-04-28 |
| EP2146961A1 (en) | 2010-01-27 |
| CA2683719A1 (en) | 2008-10-23 |
| ES2458592T3 (es) | 2014-05-06 |
| US20100105736A1 (en) | 2010-04-29 |
| RU2009141300A (ru) | 2011-05-20 |
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