EA017443B1 - Производные тетрагидрохинолина для лечения посттравматических стрессовых расстройств - Google Patents
Производные тетрагидрохинолина для лечения посттравматических стрессовых расстройств Download PDFInfo
- Publication number
- EA017443B1 EA017443B1 EA201000557A EA201000557A EA017443B1 EA 017443 B1 EA017443 B1 EA 017443B1 EA 201000557 A EA201000557 A EA 201000557A EA 201000557 A EA201000557 A EA 201000557A EA 017443 B1 EA017443 B1 EA 017443B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- formula
- pharmaceutically acceptable
- compound
- compounds
- acceptable salt
- Prior art date
Links
- 208000028173 post-traumatic stress disease Diseases 0.000 title claims abstract description 6
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- -1 trifluoromethylphenyl Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- 208000019901 Anxiety disease Diseases 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 230000009257 reactivity Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- 229940123730 Orexin receptor antagonist Drugs 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960003529 diazepam Drugs 0.000 description 4
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 3
- 230000002996 emotional effect Effects 0.000 description 3
- 208000011688 Generalised anxiety disease Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 108050000742 Orexin Receptor Proteins 0.000 description 2
- 102000008834 Orexin receptor Human genes 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000029364 generalized anxiety disease Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000013200 Stress disease Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229940000041 nervous system drug Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- 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
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IB2007054130 | 2007-10-10 | ||
| PCT/IB2008/054138 WO2009047723A2 (en) | 2007-10-10 | 2008-10-09 | Tetrahydroquinoline derivatives for treating post-traumatic stress disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201000557A1 EA201000557A1 (ru) | 2010-10-29 |
| EA017443B1 true EA017443B1 (ru) | 2012-12-28 |
Family
ID=40467356
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201000557A EA017443B1 (ru) | 2007-10-10 | 2008-10-09 | Производные тетрагидрохинолина для лечения посттравматических стрессовых расстройств |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US9532985B2 (enExample) |
| EP (1) | EP2207550B1 (enExample) |
| JP (1) | JP5883222B2 (enExample) |
| KR (1) | KR101733247B1 (enExample) |
| CN (1) | CN101820878B (enExample) |
| AR (1) | AR068768A1 (enExample) |
| AU (1) | AU2008309194B2 (enExample) |
| BR (1) | BRPI0818617A2 (enExample) |
| CA (1) | CA2699504C (enExample) |
| CY (1) | CY1114799T1 (enExample) |
| DK (1) | DK2207550T3 (enExample) |
| EA (1) | EA017443B1 (enExample) |
| ES (1) | ES2444418T3 (enExample) |
| HR (1) | HRP20140214T1 (enExample) |
| IL (1) | IL204838A (enExample) |
| MA (1) | MA31800B1 (enExample) |
| MX (1) | MX2010003711A (enExample) |
| MY (1) | MY153044A (enExample) |
| NZ (1) | NZ585086A (enExample) |
| PE (1) | PE20091010A1 (enExample) |
| PL (1) | PL2207550T3 (enExample) |
| PT (1) | PT2207550E (enExample) |
| SI (1) | SI2207550T1 (enExample) |
| TW (1) | TWI428129B (enExample) |
| UA (1) | UA99150C2 (enExample) |
| WO (1) | WO2009047723A2 (enExample) |
| ZA (1) | ZA201003251B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2669561A1 (en) | 2006-12-22 | 2008-07-03 | Actelion Pharmaceuticals Ltd | 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives |
| KR20110036069A (ko) | 2008-06-25 | 2011-04-06 | 액테리온 파마슈티칼 리미티드 | 5,6,7,8-테트라히드로-이미다조[1,5-ａ]피라진 화합물 |
| EP2402322A1 (en) | 2010-07-02 | 2012-01-04 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivative and its use as orexin receptor antagonist |
| KR101802726B1 (ko) | 2010-08-24 | 2017-11-29 | 액테리온 파마슈티칼 리미티드 | 오렉신 수용체 안타고니스트로서의 프롤린 술폰아미드 유도체 |
| MY160969A (en) | 2010-09-22 | 2017-03-31 | Eisai R&D Man Co Ltd | Cyclopropane compounds |
| CA2815179A1 (en) | 2010-11-10 | 2012-05-18 | Actelion Pharmaceuticals Ltd | Lactam derivatives useful as orexin receptor antagonists |
| WO2012085857A1 (en) | 2010-12-22 | 2012-06-28 | Actelion Pharmaceuticals Ltd | 3,8-diaza-bicyclo[4.2.0]oct-3-yl amides |
| CN103380130B (zh) | 2011-02-18 | 2015-06-17 | 埃科特莱茵药品有限公司 | 用作为食欲素拮抗剂的新颖的吡唑和咪唑衍生物 |
| WO2012114252A1 (en) | 2011-02-21 | 2012-08-30 | Actelion Pharmaceuticals Ltd | Novel indole and pyrrolopyridine amides |
| WO2013050938A1 (en) | 2011-10-04 | 2013-04-11 | Actelion Pharmaceuticals Ltd | 3,7-diazabicyclo[3.3.1]nonane and 9-oxa-3,7-diazabicyclo[3.3.1]nonane derivatives |
| EA024106B1 (ru) | 2011-11-08 | 2016-08-31 | Актелион Фармасьютиклз Лтд. | Производные 2-(1,2,3-триазол-2-ил)бензамида и 3-(1,2,3-триазол-2-ил)пиколинамида |
| PT2855453T (pt) | 2012-06-04 | 2017-03-09 | Actelion Pharmaceuticals Ltd | Derivados de benzimidazol-prolina |
| WO2014057435A1 (en) | 2012-10-10 | 2014-04-17 | Actelion Pharmaceuticals Ltd | Orexin receptor antagonists which are [ortho bi (hetero )aryl]-[2-(meta bi (hetero )aryl)-pyrrolidin-1-yl]-methanone derivatives |
| EP2970241A1 (en) | 2013-03-12 | 2016-01-20 | Actelion Pharmaceuticals Ltd. | Azetidine amide derivatives as orexin receptor antagonists |
| PL3077389T3 (pl) | 2013-12-03 | 2018-03-30 | Idorsia Pharmaceuticals Ltd | KRYSTALICZNA POSTAĆ (S)-(2-(6-CHLORO-7-METYLO-1H-BENZO[D]lMIDAZOL-2-ILO)- 2-METYLOPIROLIDYN-1-YLO)(5-METOKSY-2-(2H-1,2,3-TRIAZOL-2-ILO)FENYLO)METANONU I JEJ ZASTOSOWANIE JAKO ANTAGONISTY RECEPTORA OREKSYNY |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| UA116053C2 (uk) | 2013-12-04 | 2018-01-25 | Ідорсія Фармасьютікалз Лтд | Застосування похідних бензоімідазолу-проліну |
| MX376164B (es) | 2014-10-23 | 2025-03-07 | Eisai R&D Man Co Ltd | Composiciones y metodos para tratar el insomnio. |
| WO2019024845A1 (zh) * | 2017-08-01 | 2019-02-07 | 苏州科睿思制药有限公司 | 一种食欲素受体拮抗剂的晶型及其制备方法和用途 |
| WO2020007964A1 (en) | 2018-07-05 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 2-(2-azabicyclo[3.1.0]hexan-1-yl)-1h-benzimidazole derivatives |
| WO2020007977A1 (en) | 2018-07-06 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 7-trifluoromethyl-[1,4]diazepan derivatives |
| WO2020099511A1 (en) | 2018-11-14 | 2020-05-22 | Idorsia Pharmaceuticals Ltd | Benzimidazole-2-methyl-morpholine derivatives |
| TW202400149A (zh) | 2022-05-13 | 2024-01-01 | 瑞士商愛杜西亞製藥有限公司 | 經噻唑并芳基-甲基取代之環狀肼-n-甲醯胺衍生物 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001068609A1 (en) * | 2000-03-14 | 2001-09-20 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivatives |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
| WO2005118548A1 (en) * | 2004-03-01 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| US20070160538A1 (en) * | 2005-04-25 | 2007-07-12 | Eisai Co., Ltd. | Antianxiety drugs and a method of screening the same |
| WO2007105177A1 (en) * | 2006-03-15 | 2007-09-20 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinoline derivatives to enhance memory function |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2402322A1 (en) | 2010-07-02 | 2012-01-04 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivative and its use as orexin receptor antagonist |
-
2008
- 2008-10-07 PE PE2008001739A patent/PE20091010A1/es not_active Application Discontinuation
- 2008-10-09 TW TW097139093A patent/TWI428129B/zh not_active IP Right Cessation
- 2008-10-09 HR HRP20140214AT patent/HRP20140214T1/hr unknown
- 2008-10-09 US US12/681,802 patent/US9532985B2/en not_active Expired - Fee Related
- 2008-10-09 KR KR1020107010186A patent/KR101733247B1/ko not_active Expired - Fee Related
- 2008-10-09 AR ARP080104422A patent/AR068768A1/es unknown
- 2008-10-09 SI SI200831152T patent/SI2207550T1/sl unknown
- 2008-10-09 WO PCT/IB2008/054138 patent/WO2009047723A2/en not_active Ceased
- 2008-10-09 DK DK08807937.1T patent/DK2207550T3/da active
- 2008-10-09 MY MYPI2010001561A patent/MY153044A/en unknown
- 2008-10-09 ES ES08807937.1T patent/ES2444418T3/es active Active
- 2008-10-09 PT PT88079371T patent/PT2207550E/pt unknown
- 2008-10-09 CN CN2008801113334A patent/CN101820878B/zh not_active Expired - Fee Related
- 2008-10-09 EA EA201000557A patent/EA017443B1/ru not_active IP Right Cessation
- 2008-10-09 EP EP08807937.1A patent/EP2207550B1/en active Active
- 2008-10-09 CA CA2699504A patent/CA2699504C/en active Active
- 2008-10-09 NZ NZ585086A patent/NZ585086A/en not_active IP Right Cessation
- 2008-10-09 UA UAA201005122A patent/UA99150C2/ru unknown
- 2008-10-09 JP JP2010528515A patent/JP5883222B2/ja not_active Expired - Fee Related
- 2008-10-09 BR BRPI0818617-0A patent/BRPI0818617A2/pt not_active Application Discontinuation
- 2008-10-09 PL PL08807937T patent/PL2207550T3/pl unknown
- 2008-10-09 MX MX2010003711A patent/MX2010003711A/es active IP Right Grant
- 2008-10-09 AU AU2008309194A patent/AU2008309194B2/en not_active Ceased
-
2010
- 2010-04-06 IL IL204838A patent/IL204838A/en active IP Right Grant
- 2010-04-30 MA MA32806A patent/MA31800B1/fr unknown
- 2010-05-07 ZA ZA2010/03251A patent/ZA201003251B/en unknown
-
2014
- 2014-02-04 CY CY20141100085T patent/CY1114799T1/el unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001068609A1 (en) * | 2000-03-14 | 2001-09-20 | Actelion Pharmaceuticals Ltd. | 1,2,3,4-tetrahydroisoquinoline derivatives |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
| WO2005118548A1 (en) * | 2004-03-01 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| US20070160538A1 (en) * | 2005-04-25 | 2007-07-12 | Eisai Co., Ltd. | Antianxiety drugs and a method of screening the same |
| WO2007105177A1 (en) * | 2006-03-15 | 2007-09-20 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinoline derivatives to enhance memory function |
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