RU2005121711A - Способы лечения митохондриальных нарушений - Google Patents
Способы лечения митохондриальных нарушений Download PDFInfo
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- 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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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 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2001125913/14A RU2268732C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
| RU2005121711/14A RU2394580C2 (ru) | 1999-02-23 | 2000-02-23 | Способы лечения митохондриальных нарушений |
Family Applications Before (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) | RU2268732C2 (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 |
| 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 |
| PT1140104E (pt) * | 1998-07-31 | 2007-12-26 | Massachusetts Inst Technology | Tratamento da doença de alzheimer, in vivo, por aumento dos níveis de citidina |
| 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 |
| US20050203053A1 (en) * | 1999-07-30 | 2005-09-15 | Wurtman Richard J. | Uridine administration improves phosphatide synthesis, synaptic transmission and cogntive function |
| US6472378B2 (en) | 1998-08-31 | 2002-10-29 | Pro-Neuron, Inc. | 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 |
| US7807654B2 (en) | 1998-08-31 | 2010-10-05 | Wellstat Therapeutics Corporation | Compositions and methods for treatment of mitochondrial diseases |
| RU2268732C2 (ru) | 1999-02-23 | 2006-01-27 | Дзе Риджентс Оф Дзе Юниверсити Оф Калифорния | Способы лечения митохондриальных нарушений |
| 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 |
| WO2002083651A2 (en) * | 2001-04-11 | 2002-10-24 | Queen's University At Kingston | Pyrimidine compounds as anti-ictogenic and/or anti-epileptogenic agents |
| WO2002097124A1 (en) * | 2001-05-29 | 2002-12-05 | The University Of British Columbia | Pharmacological applications of mitochondrial dna assays |
| 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 |
| DK1888059T3 (en) | 2005-06-01 | 2015-03-30 | Edison Pharmaceuticals Inc | Redox-active therapeutic products for the treatment of mitochondrial diseases and other conditions as well as modulation of energy biomarkers |
| LT1933821T (lt) * | 2005-09-15 | 2020-11-10 | Ptc Therapeutics, Inc. | Šoninės grandinės variantai redoks aktyviųjų terapijos priemonių, skirtų mitochondrinių ligų ir kitokių būklių gydymui ir energijos biologinių žymenų moduliavimui |
| EP1986636B1 (en) | 2006-02-22 | 2013-04-24 | Edison Pharmaceuticals, Inc. | Phenol and 1,4-benzoquinone derivatives for use in the treatment of mitochondrial diseases |
| 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 |
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