KR100941527B1 - 인지 장애를 치료하기 위한 조성물 - Google Patents
인지 장애를 치료하기 위한 조성물 Download PDFInfo
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- KR100941527B1 KR100941527B1 KR1020077007141A KR20077007141A KR100941527B1 KR 100941527 B1 KR100941527 B1 KR 100941527B1 KR 1020077007141 A KR1020077007141 A KR 1020077007141A KR 20077007141 A KR20077007141 A KR 20077007141A KR 100941527 B1 KR100941527 B1 KR 100941527B1
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- South Korea
- Prior art keywords
- piperazin
- fluoro
- dihydro
- benzo
- benzyl
- Prior art date
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- 0 C*(C)N(*)** Chemical compound C*(C)N(*)** 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
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- A61K31/425—Thiazoles
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
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- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Psychology (AREA)
- Virology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Communicable Diseases (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Indole Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims (24)
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- 효과량의 조합된 선택적인 5-HT6(5-하이드록시트립타민-6)/5-HT2A(5-하이드록시트립타민-2A) 수용체 길항제 화합물 및 약학적으로 허용되는 부형제를 포함하는, 알츠하이머병, 학습과 관련된 퇴행성 장애, 학습 불능, 기억 또는 인지 기능장애, 경도 인지 손상, 노화-관련 인지 감소, 뇌 노쇠, 혈관성 치매, AIDS 연계된 치매, 전기충격으로 유도된 기억상실증, 우울증 또는 불안과 연계된 기억 손상, 파킨슨병에서의 인지 결핍, 다운증후군, 뇌졸중, 외인성 뇌 손상, 헌팅톤병 및 주의력 결핍 장애로 이루어진 군으로부터 선택된 인지 장애의 치료용 약학 조성물로서,상기 화합물이 5-HT6(5-하이드록시트립타민-6) 수용체에 대해 8 이상의 pKi 값인 친화도 및 5-HT2A(5-하이드록시트립타민-2A) 수용체에 대해 8 이상의 pKi 값인 친화도를 가지거나, 또는 5-HT6 수용체에 대해 8 이상의 pKi 값인 친화도 또는 5-HT2A 수용체에 대해 8 이상의 pKi 값인 친화도를 가지고, 도파민 D2 수용체, 히스타민 H1 수용체, 및 무스카린 M1 및 M2 수용체에 대해 30배 이상의 선택성을 가지며,이때 상기 화합물이4-벤질-6-메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(3-클로로-벤질)-6-메톡시-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-벤질-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(4-플루오로-벤질)-6-플루오로-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(3-클로로-벤질)-6-플루오로-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(3-플루오로-벤질)-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(3-클로로-벤질)-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-벤질-6-플루오로-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;1-(3-플루오로-벤질)-7-메틸-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;6-플루오로-4-(3-플루오로-벤질)-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;6-플루오로-4-(4-플루오로-벤질)-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;4-(3-클로로-벤질)-6-플루오로-2,2-다이메틸-8-피페라진-1-일-4H-벤조[1,4]옥사진-3-온;1-(3-클로로-벤질)-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;1-(3,4-다이플루오로-벤질)-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;1-(3-플루오로-벤질)-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;1-(4-플루오로-벤질)-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;1-(4-클로로-벤질)-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;1-(3-플루오로-벤질)-7-메틸-5-피페라진-1-일-3,4-다이하이드로-1H-퀴나졸린-2-온;4-(3-플루오로-페닐설포닐)-2,2-다이메틸-8-피페라진-1-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;4-(3-클로로-페닐설포닐)-2,2-다이메틸-8-피페라진-1-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;6-플루오로-4-(2-플루오로-페닐설포닐)-2,2-다이메틸-8-피페라진-1-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;6-플루오로-4-(3-플루오로-페닐설포닐)-2,2-다이메틸-8-피페라진-1-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;6-플루오로-4-(4-플루오로-페닐설포닐)-2,2-다이메틸-8-피페라진-1-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;[7-(3-플루오로-페닐설포닐)-2,3-다이하이드로-벤조[1,4]다이옥신-2-(R)-일메틸]-메틸아민;C-[7-(3-플루오로-페닐설포닐)-2,3-다이하이드로-벤조[1,4]다이옥신-2-(S)-일]-메틸아민;(7-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일메틸)-(5,5-다이메틸-1,4,5,6-테트라하이드로-피리미딘-2-일)-아민;(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일메틸)-(4,5-다이하이드로-1H-이미다졸-2-일)-아민;N-(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일메틸)-구아니딘;3-(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일)-프로피온아미딘;C-(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일)-메틸아민;(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일메틸)-메틸아민;N-(6-페닐설포닐-1,2,3,4-테트라하이드로-나프탈렌-1-일메틸)-아세트아미딘;2-[6-(2-플루오로-페닐설포닐)-1,2,3,4-테트라하이드로-나프탈렌-1-일]-에틸아민;6-페닐설포닐-4-피페리딘-4-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;1-(7-페닐설포닐-2,3-다이하이드로-벤조[1,4]옥사진-4-일)-2-(4,5-다이하이드로-1H-이미다졸-2-일)-에탄온;7-페닐설포닐-4-피페리딘-4-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;7-페닐설포닐-4-피롤리딘-3-일-3,4-다이하이드로-2H-벤조[1,4]옥사진;1-벤질-4-피페라진-1-일-1,3-다이하이드로-벤조이미다졸-2-온;1-벤질-4-(2-메틸아미노-에톡시)-1,3-다이하이드로-벤조이미다졸-2-온; 및1-벤질-4-피페라진-1-일-1,3-다이하이드로-벤조이미다졸-2-온으로 이루어진 군으로부터 선택된 화합물인, 약학 조성물.
- 삭제
- 제 8 항에 있어서,화합물이 5-HT2C(5-하이드록시트립타민-2C) 수용체에 대해 30배 이상의 선택성을 추가로 가지는 약학 조성물.
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KR1020077007141A KR100941527B1 (ko) | 2004-09-30 | 2005-09-22 | 인지 장애를 치료하기 위한 조성물 |
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EP (2) | EP2301625B1 (ko) |
JP (2) | JP4975626B2 (ko) |
KR (2) | KR100993434B1 (ko) |
CN (3) | CN101031554A (ko) |
AT (1) | ATE499147T1 (ko) |
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BR (1) | BRPI0516749B8 (ko) |
CA (1) | CA2582273C (ko) |
DE (1) | DE602005026543D1 (ko) |
ES (3) | ES2643615T3 (ko) |
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US10100010B1 (en) | 2015-04-27 | 2018-10-16 | Daewoong Pharmaceutical Co., Ltd. | 4-methoxy pyrrole derivatives or salts thereof and pharmaceutical composition comprising the same |
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EP1904483A1 (en) | 2005-07-13 | 2008-04-02 | F. Hoffmann-Roche AG | Benzimidazole derivatives as 5-ht6,5-ht24 |
AU2007263084A1 (en) * | 2006-06-20 | 2007-12-27 | F. Hoffmann-La Roche Ag | Tetralin and indane derivatives and uses thereof |
ES2358288T3 (es) * | 2007-08-01 | 2011-05-09 | Laboratorios Del Dr. Esteve S.A. | Combinación de al menos dos ligandos de 5ht6. |
WO2013055386A2 (en) * | 2011-10-03 | 2013-04-18 | The University Of Utah Research Foundation | Application of 5-ht6 receptor antagonists for the alleviation of cognitive deficits of down syndrome |
RU2624978C2 (ru) * | 2015-07-27 | 2017-07-11 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Воронежский государственный медицинский университет им. Н.Н. Бурденко" Министерства здравоохранения Российской Федерации | Способ лечения умеренного когнитивного снижения |
CN108926565A (zh) * | 2017-05-26 | 2018-12-04 | 中国科学院上海生命科学研究院 | 五羟色胺受体亚型6小分子激活剂及拮抗剂在防治阿尔茨海默症中的应用 |
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WO2001089498A2 (en) * | 2000-05-25 | 2001-11-29 | Aventis Pharma Inc | USE OF (+)-α -(2,3-DIMETHOXYPHENYL)-1-[2-(4-FLUOROPHENYL)ETHYL]-4-PIPERIDINEMETHANOL OR ITS PRODRUG IN THE TREATMENT OF SYMPTOMS OF DEMENTIA AND DOPAMINE INDUCED PSYCHOSIS |
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US10100010B1 (en) | 2015-04-27 | 2018-10-16 | Daewoong Pharmaceutical Co., Ltd. | 4-methoxy pyrrole derivatives or salts thereof and pharmaceutical composition comprising the same |
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