RU2005121711A - Способы лечения митохондриальных нарушений - Google Patents
Способы лечения митохондриальных нарушений Download PDFInfo
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- RU2005121711A RU2005121711A RU2005121711/14A RU2005121711A RU2005121711A RU 2005121711 A RU2005121711 A RU 2005121711A RU 2005121711/14 A RU2005121711/14 A RU 2005121711/14A RU 2005121711 A RU2005121711 A RU 2005121711A RU 2005121711 A RU2005121711 A RU 2005121711A
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
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- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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Claims (20)
1. Способ лечения митохондриального нарушения, предусматривающий введение субъекту, имеющему такое нарушение или имеющему риск возникновения такого нарушения, эффективного количества соединения формулы I
где R1 обозначает ОН, NHCOCH3 или NH2,
R2 обозначает Н, СО2Н или
где X обозначает С1-С22 алкил, C2-C22 алкенил или C2-C22 алкинил, с заместителями, выбранными из группы, состоящей из Н, C1-3 алкила, ОН, NH2 и галогена, или где X обозначает Н,
R3, R4 и R5 обозначают, независимо, необязательно замещенный C1-C22 алкилкарбонил, с заместителями, выбранными
из группы, состоящей из C1-3 алкила, ОН, NH2, галогена и Н, где, по меньшей мере, один из R3, R4 и R5 не является Н, для лечения посредством этого данного нарушения.
2. Способ по п.1, где необязательно замещенный алкилкарбонил является неразветвленным и имеет приблизительно 5-22 атома углерода.
3. Способ по п.1, где алкилкарбонил представляет собой карбонильное производное аминокислоты, выбранной из группы, состоящей из глицина, L-форм аланина, валина, лейцина, изолейцина, тирозина, пролина, гидроксипролина, серина, треонина, цистина, цистеина, аспарагиновой кислоты, глутаминовой кислоты, аргинина, лизина, гистидина, карнитина и орнитина.
4. Способ по п.1, где алкилкарбонил представляет собой карбонильное производное дикарбоновой кислоты, имеющей приблизительно 3-22 атома углерода.
5. Способ по п.1, где митохондриальное нарушение представляет собой недостаточность кардиолипина.
6. Способ по п.1, где митохондриальное нарушение включает недостаточность в синтетическом пути пиримидинов.
7. Способ по п.6, где недостаточность в синтетическом пути пиримидинов является недостаточностью в синтетическом пути уридина.
8. Способ по п.6, где эта недостаточность включает пониженную экспрессию и/или активность фермента в синтетическом пути уридина.
9. Способ по п.8, где этот фермент выбран из группы, состоящей из дигидрооротатдегидрогеназы (DHOD) и уридинмонофосфатсинтазы (UMPS).
10. Способ по п.1, где митохондриальное нарушение приводит к более низким, чем нормальные, уровням уридина.
11. Способ по п.1, где митохондриальное нарушение является результатом более раннего или одновременного введения фармацевтического агента.
12. Способ по п.11, где этот фармацевтический агент является ингибитором обратной транскриптазы, ингибитором протеаз или ингибитором DHOD.
13. Способ по п.12, где ингибитор обратной транскриптазы представляет собой азидотимидин (AZT), ставудин (D4T), зальцитабин (ddC), диданозин (DDI), фториодоараурацил (FIAU).
14. Способ по п.12, где ингибитор протеаз представляет собой Ritonavir, Indinavir, Saquinavir или Nelfinavir.
15. Способ по п.12, где ингибитор DHOD представляет собой Leflunomide или Brequinar.
16. Способ по п.1, дополнительно предусматривающий введение одного или нескольких кофакторов, витаминов или смесей из двух или нескольких этих веществ.
17. Способ по п.16, где этот кофактор является одним из кофермента Q и пирувата кальция или включает в себя оба.
18. Способ по п.16, где витамин выбран из группы, состоящей из тиамина (В1), рибофлавина (В2), ниацина (ВЗ), пиридоксина (В6), фолата, цианокобаламина (В12), биотина и пантотеновой кислоты.
19. Способ уменьшения или устранения одного или нескольких симптомов, ассоциированных с митохондриальным нарушением, предусматривающий введение субъекту, нуждающемуся в этом, эффективного количества соединения формулы I
где R1 обозначает ОН, NHCOCH3 или NH2,
R2 обозначает Н, CO2Н или
где X обозначает C1-C22 алкил, C2-C22 алкенил или C2-C22 алкинил, с заместителями, выбранными из группы, состоящей из Н, C1-3 алкила, ОН, NH2 и галогена, или где X обозначает Н,
R3, R4 и R5 обозначают, независимо, необязательно замещенный C1-C22 алкилкарбонил, с заместителями, выбранными из группы, состоящей из C1-3 алкила, ОН, NH2, галогена и Н, где, по меньшей мере, один из R3, R4 и R5 не является Н,
для лечения посредством этого данного нарушения.
20. Способ по п.19, где этими симптомами являются почечный канальцевый ацидоз (RTA), ослабленное зрение, деменция, припадки, кардиомиопатия, скелетная миопатия, периферическая миопатия или вегетативная миопатия.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12158899P | 1999-02-23 | 1999-02-23 | |
| US60/121,588 | 1999-02-23 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2001125913/14A Division RU2268732C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2005121711A true RU2005121711A (ru) | 2007-01-20 |
| RU2394580C2 RU2394580C2 (ru) | 2010-07-20 |
Family
ID=22397641
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2005121711/14A RU2394580C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
| RU2001125913/14A RU2268732C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2001125913/14A RU2268732C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US7638501B1 (ru) |
| EP (2) | EP1808177B1 (ru) |
| JP (1) | JP4776780B2 (ru) |
| KR (2) | KR100758712B1 (ru) |
| CN (2) | CN1191835C (ru) |
| AT (1) | ATE381935T1 (ru) |
| AU (1) | AU776437B2 (ru) |
| BR (1) | BR0008447A (ru) |
| CA (1) | CA2362925C (ru) |
| DE (1) | DE60037578T2 (ru) |
| DK (1) | DK1171137T3 (ru) |
| ES (1) | ES2298130T3 (ru) |
| HU (1) | HU230191B1 (ru) |
| IL (3) | IL144964A0 (ru) |
| MX (1) | MXPA01008549A (ru) |
| NZ (1) | NZ513926A (ru) |
| PT (1) | PT1171137E (ru) |
| RU (2) | RU2394580C2 (ru) |
| WO (1) | WO2000050043A1 (ru) |
| ZA (1) | ZA200107727B (ru) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6306909B1 (en) | 1997-03-12 | 2001-10-23 | Queen's University At Kingston | Anti-epileptogenic agents |
| US20050203053A1 (en) * | 1999-07-30 | 2005-09-15 | Wurtman Richard J. | Uridine administration improves phosphatide synthesis, synaptic transmission and cogntive function |
| US8518882B2 (en) * | 1998-07-31 | 2013-08-27 | Massachusetts Institute Of Technology | Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same |
| ES2294850T3 (es) * | 1998-07-31 | 2008-04-01 | Massachusetts Institute Of Technology | Tratamiento de la enfermedad de alzheimer mediante el aumento de los niveles de citidina in vivo. |
| US8314064B2 (en) * | 1998-07-31 | 2012-11-20 | Massachusetts Institute Of Technology | Uridine administration stimulates membrane production |
| US8143234B2 (en) * | 1998-07-31 | 2012-03-27 | Massachusetts Institute Of Technology | Uridine administration improves phosphatide synthesis, synaptic transmission and cognitive function |
| US7807654B2 (en) | 1998-08-31 | 2010-10-05 | Wellstat Therapeutics Corporation | Compositions and methods for treatment of mitochondrial diseases |
| US7915233B1 (en) | 1998-08-31 | 2011-03-29 | Wellstat Therapeutics Corporation | Compositions and methods for treatment of mitochondrial diseases |
| US6472378B2 (en) | 1998-08-31 | 2002-10-29 | Pro-Neuron, Inc. | Compositions and methods for treatment of mitochondrial diseases |
| PT1171137E (pt) | 1999-02-23 | 2008-03-17 | Univ California | Utilização de triacetiluridina para o tratamento de perturbações mitocondriais |
| US6727231B1 (en) * | 2000-10-12 | 2004-04-27 | Repligen Corporation | Uridine therapy for patients with elevated purine levels |
| DE10110355A1 (de) * | 2001-03-03 | 2002-09-12 | Ulrich Walker | Bekämpfung von Nebenwirkungen |
| EP1385831A2 (en) * | 2001-04-11 | 2004-02-04 | Queen's University At Kingston | Pyrimidine compounds as anti-ictogenic and/or anti-epileptogenic agents |
| ES2269690T3 (es) * | 2001-05-29 | 2007-04-01 | The University Of British Columbia | Aplicaciones farmacologicas de los ensayos de adn mitocondrial. |
| JP2004182705A (ja) * | 2002-10-11 | 2004-07-02 | Yasutoshi Koga | ミトコンドリア機能異常に起因する疾患における臨床症状発現の予防・治療用組成物 |
| JP2006515891A (ja) * | 2003-01-17 | 2006-06-08 | シーブイ・セラピューティクス・インコーポレイテッド | 循環器疾患の処置に有効な置換ヘテロ環化合物 |
| EP2471530B1 (en) | 2005-06-01 | 2017-01-11 | Edison Pharmaceuticals, Inc. | Redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomarkers |
| EA021818B1 (ru) * | 2005-09-15 | 2015-09-30 | Эдисон Фармасьютикалз, Инк. | Варианты хвостовой части редокс-активных лекарственных средств для лечения митохондриальных болезней и модуляция биомаркера энергетического обмена q10 |
| JP5374162B2 (ja) | 2006-02-22 | 2013-12-25 | エジソン ファーマシューティカルズ， インコーポレイテッド | ミトコンドリア病および他の症状の処置のためのレドックス活性化治療の側鎖変異体およびエネルギーバイオマーカーの調節 |
| US8748405B2 (en) | 2007-01-26 | 2014-06-10 | City Of Hope | Methods and compositions for the treatment of cancer or other diseases |
| EP2217075A4 (en) | 2007-11-02 | 2012-01-25 | Massachusetts Inst Technology | METHODS OF CONTROLLING ADHESION TO URIDINE FOOD SUPPLEMENTATION AND THEIR USE |
| CN101612110B (zh) * | 2008-06-23 | 2012-07-25 | 欣凯医药化工中间体（上海）有限公司 | 三乙酰尿苷缓释制剂及其制备方法 |
| CA2736250C (en) | 2008-09-10 | 2016-12-20 | Edison Pharmaceuticals, Inc. | Treatment of pervasive developmental disorders with redox-active therapeutics |
| EP2556832B1 (en) * | 2011-08-12 | 2017-07-19 | Universitätsklinikum Freiburg | Uridine and uridine analogues for use in the treatment of chronic obstructive pulmonary disease |
| WO2015106255A1 (en) | 2014-01-13 | 2015-07-16 | City Of Hope | Multivalent oligonucleotide assemblies |
| EP3182980B1 (en) * | 2014-08-19 | 2020-10-14 | Wellstat Therapeutics Corporation | Treatment of glycosylation deficiency diseases |
| FR3027804A1 (fr) * | 2014-10-31 | 2016-05-06 | Centre Nat Rech Scient | Utilisation d'un inhibiteur de transcriptase inverse dans la prevention et le traitement des maladies degeneratives |
| BR112017022578A2 (pt) | 2015-05-29 | 2018-07-17 | The Board Of Trustees Of The Leland Stanford Junior University | agentes nucleosídicos para a redução da atividade deletéria de genes que contém repetições estendidas de nucleotídeos |
| HUE062134T2 (hu) | 2015-06-05 | 2023-09-28 | Fundacio Hospital Univ Vall Dhebron Institut De Recerca | Mitokondriális betegségek kezelése |
| HUE046399T2 (hu) * | 2015-06-17 | 2020-03-30 | Univ Columbia | Deoxinukleozid terápia kiegyensúlyozatlan nukleotid pool által okozott betegségek, ideértve a mitokondriális DNS depléciós szindrómát, kezelésére |
| CN113024369A (zh) | 2015-12-17 | 2021-06-25 | Ptc医疗公司 | 用于治疗氧化应急障碍的化合物 |
| KR101981843B1 (ko) | 2016-09-13 | 2019-05-23 | 울산대학교 산학협력단 | 일산화탄소 또는 일산화탄소 공급체를 유효성분으로 함유하는 미토콘드리아 기능 개선용 조성물 |
| JP2021519334A (ja) | 2018-03-26 | 2021-08-10 | クリア クリーク バイオ， インコーポレイテッド | ジヒドロオロト酸デヒドロゲナーゼを阻害するための組成物および方法 |
| JP2022546611A (ja) * | 2019-09-05 | 2022-11-04 | ミトレインボー セラピューティクス，インコーポレーテッド | ミトコンドリアｄｎａ枯渇障害の処置 |
| KR102290596B1 (ko) * | 2020-09-10 | 2021-08-19 | 주식회사 파이안바이오테크놀로지 | 분리된 미토콘드리아를 포함하는 주사용 조성물 및 이의 용도 |
| EP3970713A1 (en) | 2020-09-16 | 2022-03-23 | GV Squared S.r.l. | Pharmaceutical composition comprising uridine and pyruvate for regulating the profileration, activity and survival of immune cells |
| CN113116900B (zh) * | 2021-04-14 | 2022-07-08 | 兰州大学 | 一类核苷类似物在制备预防和/或治疗脑血管疾病药物中的应用 |
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| WO1989003837A1 (en) * | 1987-10-28 | 1989-05-05 | Pro-Neuron, Inc. | Acylated uridine and cytidine and uses thereof |
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| US6348451B1 (en) | 1987-10-28 | 2002-02-19 | Pro-Neuron, Inc. | Acyl deoxyribonucleoside derivatives and uses thereof |
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| ATE271614T1 (de) * | 1992-05-28 | 2004-08-15 | Ct For Molecular Biology And M | Quinone-derivate zur verbesserung der zellulare bioenergie |
| US5567689A (en) | 1993-08-13 | 1996-10-22 | The Uab Research Foundation | Methods for increasing uridine levels with L-nucleosides |
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| JP3808121B2 (ja) * | 1995-01-09 | 2006-08-09 | 日本メジフィジックス株式会社 | 低酸素症またはミトコンドリア機能障害診断剤 |
| US5962459A (en) | 1996-05-28 | 1999-10-05 | Polifarma S.P.A. | Therapeutic active agent for treatment of neuron degenerative diseases |
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