RU2012136457A - Новые композиции для уменьшения аb 42 синтеза и их применение в лечении болезни альцгеймера (ad) - Google Patents
Новые композиции для уменьшения аb 42 синтеза и их применение в лечении болезни альцгеймера (ad) Download PDFInfo
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- RU2012136457A RU2012136457A RU2012136457/04A RU2012136457A RU2012136457A RU 2012136457 A RU2012136457 A RU 2012136457A RU 2012136457/04 A RU2012136457/04 A RU 2012136457/04A RU 2012136457 A RU2012136457 A RU 2012136457A RU 2012136457 A RU2012136457 A RU 2012136457A
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- 208000024827 Alzheimer disease Diseases 0.000 title claims 8
- 230000015572 biosynthetic process Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract 10
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract 7
- 125000003118 aryl group Chemical group 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims abstract 4
- 239000000651 prodrug Substances 0.000 claims abstract 3
- 229940002612 prodrug Drugs 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 125000003342 alkenyl group Chemical group 0.000 claims abstract 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 2
- 125000001589 carboacyl group Chemical group 0.000 claims abstract 2
- 229910052736 halogen Inorganic materials 0.000 claims abstract 2
- 150000002367 halogens Chemical class 0.000 claims abstract 2
- 125000001424 substituent group Chemical group 0.000 claims abstract 2
- 206010012289 Dementia Diseases 0.000 claims 3
- 208000032382 Ischaemic stroke Diseases 0.000 claims 3
- 208000018737 Parkinson disease Diseases 0.000 claims 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 230000005494 condensation Effects 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 0 *C(c1cccnc1)=O Chemical compound *C(c1cccnc1)=O 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
1. Соединение формулы (I)или его фармацевтически приемлемая соль, пролекарство или стереоизомер, гдеX выбран из O, NR", S или замещенного или незамещенного алкилена;L представляет собой связь или замещенный или незамещенный алкилен, предпочтительно замещенный или незамещенный Cалкилен, и предпочтительно заместители выбирают из R;X и L вместе с положениями их присоединения могут образовывать замещенный или незамещенный циклоалкил или замещенный или незамещенный гетероциклил;Y представляет собой связь, -C(O)-, -S(O)-, NR" или замещенный или незамещенный алкилен;Rвыбран из H, замещенного или незамещенного алкила или замещенного или незамещенного циклоалкила;Rвыбран из H, (CH)OR', замещенного или незамещенного алкила, замещенного или незамещенного алкенила, замещенного или незамещенного алканоила, замещенного или незамещенного арила, замещенного или незамещенного аралкила, замещенного или незамещенного гетероциклила или замещенного или незамещенного циклоалкила;Rвыбран из H, OH, галогена, NR", C(O)R", C(O)NR", замещенного или незамещенного алкила, замещенного или незамещенного алкоила или замещенного или незамещенного циклоалкила;Rвыбран из H, OR', C(O)R', C(O)R', NR', N(NR")NR', SR', SOR', SONR', NSOR', C(O)NR', (CH)OR', (CH)SR', замещенного или незамещенного алкила, замещенного или незамещенного арила, замещенного или незамещенного циклоалкила или замещенного или незамещенного гетероциклила;n представляет собой целое 0-5;R' и R" независимо выбраны из H, замещенного или незамещенного алкила, замещенного или незамещенного арила, замещенного или незамещенного циклоалкила или замещенного или незамещенного гетероциклила.2. Способ получения соединения формулы (I) по п.1, включа�
Claims (10)
1. Соединение формулы (I)
или его фармацевтически приемлемая соль, пролекарство или стереоизомер, где
X выбран из O, NR", S или замещенного или незамещенного алкилена;
L представляет собой связь или замещенный или незамещенный алкилен, предпочтительно замещенный или незамещенный C1-4 алкилен, и предпочтительно заместители выбирают из Ra;
X и L вместе с положениями их присоединения могут образовывать замещенный или незамещенный циклоалкил или замещенный или незамещенный гетероциклил;
Y представляет собой связь, -C(O)-, -S(O)2-, NR" или замещенный или незамещенный алкилен;
R1 выбран из H, замещенного или незамещенного алкила или замещенного или незамещенного циклоалкила;
R2 выбран из H, (CH2)nOR', замещенного или незамещенного алкила, замещенного или незамещенного алкенила, замещенного или незамещенного алканоила, замещенного или незамещенного арила, замещенного или незамещенного аралкила, замещенного или незамещенного гетероциклила или замещенного или незамещенного циклоалкила;
R3 выбран из H, OH, галогена, NR", C(O)2R", C(O)NR", замещенного или незамещенного алкила, замещенного или незамещенного алкоила или замещенного или незамещенного циклоалкила;
Ra выбран из H, OR', C(O)2R', C(O)R', NR', N(NR")NR', SR', SO2R', SO2NR', NSO2R', C(O)NR', (CH2)nOR', (CH2)nSR', замещенного или незамещенного алкила, замещенного или незамещенного арила, замещенного или незамещенного циклоалкила или замещенного или незамещенного гетероциклила;
n представляет собой целое 0-5;
R' и R" независимо выбраны из H, замещенного или незамещенного алкила, замещенного или незамещенного арила, замещенного или незамещенного циклоалкила или замещенного или незамещенного гетероциклила.
4. Фармацевтическая композиция, содержащая терапевтически эффективное количество соединения формулы (I) или его фармацевтически приемлемую соль, стереоизомер или пролекарство формулы (I) и фармацевтически приемлемый носитель.
5. Применение соединения по п.1 для лечения или снижения тяжести болезни Альцгеймера (AD), деменции и других нейродегенеративных расстройств, выбранных из группы, состоящей из ишемического инсульта и болезни Паркинсона.
6. Способ лечения или снижения тяжести болезни Альцгеймера (AD), деменции и других нейродегенеративных расстройств, таких как ишемический инсульт, болезнь Паркинсона, включающий введение пациенту соединения по п.1 или 4.
10. Применение соединений по п.п.7-9 для лечения или снижения тяжести болезни Альцгеймера (AD), деменции и других нейродегенеративных расстройств, выбранных из группы, состоящей из ишемического инсульта и болезни Паркинсона.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN198/MUM/2010 | 2010-01-25 | ||
| IN198MU2010 | 2010-01-25 | ||
| US39570210P | 2010-05-17 | 2010-05-17 | |
| US61/395,702 | 2010-05-17 | ||
| PCT/IB2011/050290 WO2011089576A2 (en) | 2010-01-25 | 2011-01-22 | NOVEL COMPOSITIONS FOR REDUCING Aß 42 PRODUCTION AND THEIR USE IN TREATING ALZHEIMER'S DISEASE (AD) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2012136457A true RU2012136457A (ru) | 2014-03-10 |
Family
ID=43797804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012136457/04A RU2012136457A (ru) | 2010-01-25 | 2011-01-22 | Новые композиции для уменьшения аb 42 синтеза и их применение в лечении болезни альцгеймера (ad) |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US8846721B2 (ru) |
| EP (1) | EP2528898A2 (ru) |
| JP (1) | JP5945227B2 (ru) |
| KR (1) | KR20120123075A (ru) |
| CN (1) | CN102712595B (ru) |
| AU (1) | AU2011208357A1 (ru) |
| CA (1) | CA2786666A1 (ru) |
| MX (1) | MX2012008530A (ru) |
| RU (1) | RU2012136457A (ru) |
| WO (1) | WO2011089576A2 (ru) |
| ZA (1) | ZA201205332B (ru) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8846721B2 (en) * | 2010-01-25 | 2014-09-30 | Kareus Therapeutics Sa | Compositions for reducing aβ 42 production and their use in treating alzheimer's disease (AD) |
| CN112500338A (zh) | 2013-03-15 | 2021-03-16 | 全球血液疗法股份有限公司 | 化合物及其用于调节血红蛋白的用途 |
| EA202092627A1 (ru) | 2013-11-18 | 2021-09-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| CN108704125A (zh) * | 2018-06-20 | 2018-10-26 | 深圳大学 | 一种治疗二型糖尿病的疫苗、制备方法及应用 |
| CN115894437B (zh) * | 2022-11-21 | 2024-02-23 | 南京师范大学 | 一种丁香酚硫化氢衍生物及其制备方法与应用 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1097664A (en) * | 1965-11-10 | 1968-01-03 | Kyoto Pharma Ind | 3-(o-methoxyphenoxy)-1,2-propanediol nicotinates |
| FR2433505A1 (fr) * | 1978-08-18 | 1980-03-14 | Soissonnais Sucrerie | Procede de fabrication des acides phenoxylactiques, de leurs derives et produits obtenus |
| HU195492B (en) * | 1984-07-27 | 1988-05-30 | Boehringer Biochemia Srl | Process for producing 2-substituted thiazolidine derivatives with antitussive and mucus regulating action and pharmaceuticals comprising these compounds as active ingredient |
| US4659722A (en) * | 1984-08-20 | 1987-04-21 | Nippon Kayaku Kabushiki Kaisha | Bactericidal N-(2,2,2 trichloroethyl)pyridinecarboxamides |
| JPS63313040A (ja) * | 1987-06-16 | 1988-12-21 | Univ Nagoya | 気・固系流動層の気泡測定方法およびその装置 |
| TR199902432T2 (xx) * | 1997-04-04 | 2000-01-21 | Prizer Products Inc. | Nikotinamid t�revleri. |
| CA2376892A1 (en) * | 1999-06-29 | 2001-01-04 | The Uab Research Foundation | Methods of treating fungal infections with inhibitors of nad synthetase enzyme |
| BR0309972A (pt) * | 2002-05-16 | 2005-03-01 | Bayer Cropscience Gmbh | Derivados de piridina carboxamida e seu uso como pesticidas |
| KR20050025189A (ko) * | 2002-07-27 | 2005-03-11 | 아스트라제네카 아베 | 화학 화합물 |
| WO2008013963A2 (en) * | 2006-07-28 | 2008-01-31 | University Of Connecticut | Fatty acid amide hydrolase inhibitors |
| WO2008065500A2 (en) * | 2006-11-30 | 2008-06-05 | Pfizer Products Inc. | Heteroaryl amides as type i glycine transport inhibitors |
| KR20100019489A (ko) * | 2007-05-09 | 2010-02-18 | 노파르티스 아게 | Pi3k 지질 키나제 억제제로서의 치환된 이미다조피리다진 |
| JP2011520809A (ja) * | 2008-05-05 | 2011-07-21 | アムジエン・インコーポレーテツド | γセクレターゼモジュレーターとしての尿素化合物 |
| EP2310004A1 (en) * | 2008-07-11 | 2011-04-20 | Kareus Therapeutics SA | Niacin compositions for reduction of amyloid beta peptide 42 (abeta 42) production and for treatment of alzheimer's disease (ad) |
| US8846721B2 (en) * | 2010-01-25 | 2014-09-30 | Kareus Therapeutics Sa | Compositions for reducing aβ 42 production and their use in treating alzheimer's disease (AD) |
-
2011
- 2011-01-22 US US13/574,886 patent/US8846721B2/en not_active Expired - Fee Related
- 2011-01-22 JP JP2012549459A patent/JP5945227B2/ja not_active Expired - Fee Related
- 2011-01-22 EP EP11708084.6A patent/EP2528898A2/en not_active Withdrawn
- 2011-01-22 WO PCT/IB2011/050290 patent/WO2011089576A2/en not_active Ceased
- 2011-01-22 CA CA2786666A patent/CA2786666A1/en not_active Abandoned
- 2011-01-22 KR KR1020127020415A patent/KR20120123075A/ko not_active Ceased
- 2011-01-22 CN CN201180006794.7A patent/CN102712595B/zh not_active Expired - Fee Related
- 2011-01-22 RU RU2012136457/04A patent/RU2012136457A/ru not_active Application Discontinuation
- 2011-01-22 AU AU2011208357A patent/AU2011208357A1/en not_active Abandoned
- 2011-01-22 MX MX2012008530A patent/MX2012008530A/es active IP Right Grant
-
2012
- 2012-07-17 ZA ZA2012/05332A patent/ZA201205332B/en unknown
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2014
- 2014-08-26 US US14/469,366 patent/US9464053B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102712595A (zh) | 2012-10-03 |
| MX2012008530A (es) | 2013-02-21 |
| EP2528898A2 (en) | 2012-12-05 |
| US20140364457A1 (en) | 2014-12-11 |
| WO2011089576A3 (en) | 2011-11-03 |
| JP5945227B2 (ja) | 2016-07-05 |
| CN102712595B (zh) | 2015-04-22 |
| US9464053B2 (en) | 2016-10-11 |
| JP2013533843A (ja) | 2013-08-29 |
| CA2786666A1 (en) | 2011-07-28 |
| WO2011089576A2 (en) | 2011-07-28 |
| US20120322831A1 (en) | 2012-12-20 |
| AU2011208357A1 (en) | 2012-08-09 |
| ZA201205332B (en) | 2014-03-26 |
| KR20120123075A (ko) | 2012-11-07 |
| US8846721B2 (en) | 2014-09-30 |
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