KR950702829A - 신경계 퇴행성 질환의 치료에 유용한 아나바세인 유도체 - Google Patents

신경계 퇴행성 질환의 치료에 유용한 아나바세인 유도체 Download PDF

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KR950702829A
KR950702829A KR1019950700698A KR19950700698A KR950702829A KR 950702829 A KR950702829 A KR 950702829A KR 1019950700698 A KR1019950700698 A KR 1019950700698A KR 19950700698 A KR19950700698 A KR 19950700698A KR 950702829 A KR950702829 A KR 950702829A
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methoxy
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윌리암 알. 켐
존 에이. 졸테위츠
에드윈 엠. 메이어
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카렌 앤 홀브르크
유니버시티 오브 플로리다 리서치 파운데이션, 인코포레이티드
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    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61P25/28—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
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Abstract

신규의 아나바세인과 아나바신 유도체는 뇌콜린 전달을 촉진시키는데 유용하고, 신경계의 퇴행성 질환의 치료에 유용하다.

Description

신경계 퇴행성 질환의 치료에 유용한 아나바세인 유도체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 다음의 약물지입에 따른 수동적 회피행동, 이때 화합물 A는 3-[(2.4-디하이드록시)벤질리딘] 아나베이신, 화합물 B는3-[(2-하이드록시-4-메톡시)벤질리딘]아나베이신, 화합물 C는 5'-메틸아나베이신을 각각 나타낸다.
제2도는 다음의 약물주입에 따른 수동적 회피행동으로, 이때 화합물A는 3-[(2,4-디프로폭시)벤질리딘] 아나베이신, 화합물 B는 3-[(2,4-디펜톡시)벤질리딘]아나베이신, 화합물 C는 3-[(2.4-디메톡시)벤질리딘]2-페닐-3,4,5,6-테트라하이드로피리딘을 각각 나타낸다.
제3도는 상이한 약량에서 활성 회피행동의 GTS 효과.
제4도는 활성 회피행동에서 CTS와 THA의 효과.

Claims (25)

  1. 다음 구조식의 또는 이의 제약학적 수용가능한 염의 화합물 :
    이때, 질소원소를 포함하는 6원소링의 1과 2위치 사이의 점선을 광학적 결합을 나타내는 것으로 Y는 질소 또는 탄소이고, R1은 수소 또는 C1-C4 알킬; 그리고 R2는 수소, C1-C4 알킬 또는 =CH-X이고 이때 X는 각 알킬에서 1내지 4개 탄소를 가지는 N, N-디알킬아미노에 의해 선택적으로 치환된 나프틸, 알킬, 퓨릴, 퓨릴아크로일 또는
    에서 1내지 4개 탄소를 가지는 N, N-디알킬아미노에 의해 선택적으로 치환된 스티릴이고, 이때 R3, R4, R5는 알킬, 아미노, 시아노, N, N-디알킬아미노, 알킬, 할로, 하이드록실과 니트로 각각에서 1내지 4개 탄소를 가지는 N, N-디알킬아미노 각각에서 1내지 4개 탄소를 가지는 N, N-디알킬아미노에 의해 선택적으로 치환된 수소, C1-C4 알킬, C1-C6 알콕시에서 선택된 것이고, 이때 질소원소를 포함하는 6 원소고리의 1내지 2위치에 이중결합이 있는 경우, R1은 수소이고, R2는 1-메틸, 벤질리딘 그리고 (4-디메틸아미노) 벤질리딘이 아니며, 또한 질소를 포함하는 6원소고리의 1내지 2위치에 단일결합이 있는 경우, R1은 수소 R2는 1-메틸이 아니며, 구조식에서 질소를 포함하는 6원소고리의 1내지 2위치에 단일결합인 경우에 R1은 2'-메틸이고, R2는 수소가 아니며 Y가 탄소이면 R2는 =CH-X이다.
  2. 제1항에 있어서, 질소를 포함하는 6-원소고리의 1과 2위치에 이중결합이 있고 Y는 질소인 것을 특징으로 하는 화합물.
  3. 제2항에 있어서, R1이 수소이고 R2는 3-메틸, 4-메틸, 5-메틸 또는 6-메틸인 것을 특징으로 하는 화합물.
  4. 제2항에 있어서, R1이 수소이고 2-메틸, 4-메틸, 5-메틸 또는 6-메틸과 R2는 것을 특징으로 하는 화합물.
  5. 제1항에 있어서, 질소를 포함하는 6원소 고리의 1과 2위치에 단일결합이 있고 Y가 질소인 것을 특징으로 하는 화합물.
  6. 제1항에 있어서, R2는 =CH-X이고 Y는 질소인 것을 특징으로 하는 화합물.
  7. 제6항에 있어서, X가 스티릴인 것을 특징으로 하는 화합물.
  8. 제7항에 있어서, 스티릴기는 4-디메틸아미노에 의해 치환된 것을 특징으로 하는 화합물.
  9. 제6항에 있어서, X는
    인 것을 특징으로 하는 화합물.
  10. 제9항에 있어서, 패닐링의 4번위치에 부착된 R3는 아미노, 하이드록실, 클로로, 시아노, 디메틸아미노, 메틸, 메톡시, 니트로에서 선택되고 R4 와 R5는 수소인 것을 특징으로 하는 화합물.
  11. 제9항에 있어서, R1은 수소이고, R3와 R4는 메톡시이고 R5는 수소인 것을 특징으로 하는 화합물.
  12. 제11항에 있어서, R3는 2-메톡시이고 R4는 4-메톡시인 것을 특징으로 하는 화합물.
  13. 제9항에 있어서, R1은 수소이고, R3, R4, R5는 모두 메톡시인 것을 특징으로 하는 화합물.
  14. 제13항에 있어서, R3는 4-메톡시인 것을 특징으로 하는 화합물.
  15. 제9항에 있어서, R1은 수소이고, 질소를 포함하는 6원소 고리의 1과 2위치에 단일결합인 것을 특징으로 하는 화합물.
  16. 제15항에 있어서, R3는 4-메틸아미노이고, R$와 R5는 수소인 것을 특징으로 하는 화합물.
  17. 제9항에 있어서, 질소를 포함하는 6원소고리의 1과 2위치에 이중결합인 것을 특징으로 하는 화합물.
  18. 제6항에 있어서, X는 퓨릴 또는 퓨릴아크로일인 것을 특징으로 하는 화합물.
  19. 제1항에 있어서, Y는 탄소이고, 질소를 포함하는 6원소고리의 1과 2위치에 이중결합인 것을 특징으로 하는 화합물.
  20. 제19항에 있어서, X는
    인 것을 특징으로 하는 화합물.
  21. 제20항에 있어서, R3과 R4는 메톡시이고, R5는 수소인 것을 특징으로 하는 화합물.
  22. 제21항에 있어서, R3과 2-메톡시이고 R4는 4-메톡시인 것을 특징으로 하는 화합물.
  23. 제1항에 따른 화합물의 치료요법적 효과량을 동물에 투여하는 것으로 구성된 퇴행성 신경질환의 치료방법.
  24. 제23항에 있어서, 동물은 사람이고, 신경성 질환은 알즈마이어 질환과 파킨슨 질환에서 선택되는 것을 특징으로 하는 방법.
  25. 제1항에 따른 화합물의 치료요법적 효과량과 제약학적 수용가능한 담체로 구성되고, 동물의 퇴행성 신경질환을 치료하는데 적합한 것을 특징으로 하는 제약학적 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950700698A 1992-08-31 1993-08-31 신경계의 퇴행성 질환의 치료에 유용한 아나바세인 유도체 Expired - Fee Related KR100272614B1 (ko)

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US93842792A 1992-08-31 1992-08-31
PCT/US1993/008192 WO1994005288A1 (en) 1992-08-31 1993-08-31 Anabaseine derivatives useful in the treatment of degenerative diseases of the nervous system
US938427 2001-08-24

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KR100272614B1 KR100272614B1 (ko) 2000-11-15

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US (1) US5741802A (ko)
EP (1) EP0659078B1 (ko)
JP (1) JP3034953B2 (ko)
KR (1) KR100272614B1 (ko)
AT (1) ATE230989T1 (ko)
AU (1) AU674541B2 (ko)
CA (1) CA2142610C (ko)
DE (1) DE69332641T2 (ko)
WO (1) WO1994005288A1 (ko)

Families Citing this family (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0659078B1 (en) * 1992-08-31 2003-01-15 University Of Florida Research Foundation, Inc. Anabaseine derivatives useful in the treatment of degenerative diseases of the nervous system
US5977144A (en) * 1992-08-31 1999-11-02 University Of Florida Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines
US5723477A (en) * 1994-11-10 1998-03-03 Sibia Neurosciences, Inc. Modulators of acetylcholine receptors
US5703100A (en) * 1994-11-10 1997-12-30 Sibia Neurosciences, Inc. Modulators of acetylcholine receptors
US5705512A (en) * 1994-11-10 1998-01-06 Sibia Neurosciences, Inc. Modulators of acetylcholine receptors
US5677459A (en) * 1994-11-10 1997-10-14 Sibia Neurosciences, Inc. Methods for the preparation of modulators of acetylcholine receptors
US5594011A (en) * 1994-11-10 1997-01-14 Sibia Neurosciences, Inc. Modulators of acetylcholine receptors
US6194581B1 (en) 1995-04-07 2001-02-27 Merck & Co., Inc. Substituted pyridines useful as modulators of acetylcholine receptors
US5794887A (en) 1995-11-17 1998-08-18 Komerath; Narayanan M. Stagnation point vortex controller
ATE273007T1 (de) 1997-05-29 2004-08-15 Lundbeck & Co As H Behandlung der schizophrenie und der psychose
US6708055B2 (en) * 1998-08-25 2004-03-16 University Of Florida Method for automated analysis of apical four-chamber images of the heart
US6346124B1 (en) 1998-08-25 2002-02-12 University Of Florida Autonomous boundary detection system for echocardiographic images
US6277855B1 (en) 2000-04-21 2001-08-21 Inspire Pharmaceuticals, Inc. Method of treating dry eye disease with nicotinic acetylcholine receptor agonists
US6448276B1 (en) 2000-05-17 2002-09-10 Inspire Pharmaceuticals, Inc. Method for treating vaginal dryness with nicotinic acetylcholine receptor agonists
US8914114B2 (en) 2000-05-23 2014-12-16 The Feinstein Institute For Medical Research Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
US20030162770A1 (en) 2002-02-22 2003-08-28 Davis Bonnie M. Use of modulators of nicotinic receptors for treatment of cognitive dysfunction
US20040048795A1 (en) * 2002-02-26 2004-03-11 North Shore-Long Island Jewish Research Institute Inhibition of inflammatory cytokine production by stimulation of brain muscarinic receptors
JP2006501246A (ja) 2002-08-30 2006-01-12 メモリー・ファーマシューティカルズ・コーポレイション 神経変性疾患の治療において有用なアナバセイン誘導体
MXPA05003317A (es) 2002-09-25 2005-07-05 Memory Pharm Corp Indazoles, benzotiazoles y benzoisotiazoles asi como preparacion y usos de los mismos.
US7238715B2 (en) * 2002-12-06 2007-07-03 The Feinstein Institute For Medical Research Treatment of pancreatitis using alpha 7 receptor-binding cholinergic agonists
WO2004052365A2 (en) * 2002-12-06 2004-06-24 North Shore-Long Island Jewish Research Institute Inhibition of inflamation using alpha 7 receptor-binding cholinergic agonists
RU2259364C1 (ru) * 2004-04-01 2005-08-27 Общество С Ограниченной Ответственностью "Исследовательский Институт Химического Разнообразия" Азагетероциклы, включающие фрагмент пиперидин-2-ила-, фокусированные библиотеки и фармацевтические композиции
US8729129B2 (en) * 2004-03-25 2014-05-20 The Feinstein Institute For Medical Research Neural tourniquet
US10912712B2 (en) 2004-03-25 2021-02-09 The Feinstein Institutes For Medical Research Treatment of bleeding by non-invasive stimulation
NZ550534A (en) 2004-03-25 2009-07-31 Memory Pharm Corp Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof
WO2005123075A2 (en) * 2004-06-08 2005-12-29 University Of Florida Research Foundation, Inc. Controlling angiogenesis with anabaseine analogs
US11207518B2 (en) 2004-12-27 2021-12-28 The Feinstein Institutes For Medical Research Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway
CN102793972A (zh) 2004-12-27 2012-11-28 范因斯坦医学研究院 通过电刺激迷走神经治疗炎症性疾病
WO2006133303A1 (en) * 2005-06-07 2006-12-14 University Of Florida Research Foundation, Inc. Alpha 7 nicotinic receptor selective ligands
US8316104B2 (en) 2005-11-15 2012-11-20 California Institute Of Technology Method and apparatus for collaborative system
US7662965B2 (en) 2006-01-26 2010-02-16 Cornerstone Therapeutics, Inc. Anabaseine derivatives, pharmaceutical compositions and method of use thereof
SA08290475B1 (ar) 2007-08-02 2013-06-22 Targacept Inc (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه
US8391970B2 (en) 2007-08-27 2013-03-05 The Feinstein Institute For Medical Research Devices and methods for inhibiting granulocyte activation by neural stimulation
WO2009146031A1 (en) * 2008-03-31 2009-12-03 University Of South Florida Methods of treating disease-induced ataxia and non-ataxic imbalance
US9211409B2 (en) * 2008-03-31 2015-12-15 The Feinstein Institute For Medical Research Methods and systems for reducing inflammation by neuromodulation of T-cell activity
US9662490B2 (en) 2008-03-31 2017-05-30 The Feinstein Institute For Medical Research Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug
US20090275997A1 (en) * 2008-05-01 2009-11-05 Michael Allen Faltys Vagus nerve stimulation electrodes and methods of use
EP2300012A4 (en) * 2008-05-23 2011-07-06 Univ South Florida METHOD FOR TREATING PERIPHERAL SENSORY NERVE LOSS WITH COMPOUNDS WITH NICOTIC ACIDYLCHOLINE RECEPTOR EFFECT
ES2452484T3 (es) 2008-11-18 2014-04-01 Setpoint Medical Corporation Dispositivos para optimizar la colocación de electrodos para la estimulación antiinflamatoria
TW201031664A (en) 2009-01-26 2010-09-01 Targacept Inc Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide
US9211410B2 (en) 2009-05-01 2015-12-15 Setpoint Medical Corporation Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
US8996116B2 (en) 2009-10-30 2015-03-31 Setpoint Medical Corporation Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction
WO2010144578A2 (en) 2009-06-09 2010-12-16 Setpoint Medical Corporation Nerve cuff with pocket for leadless stimulator
JP2013502427A (ja) * 2009-08-21 2013-01-24 ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド アナバセイン化合物の制御放出製剤およびその使用
US9833621B2 (en) 2011-09-23 2017-12-05 Setpoint Medical Corporation Modulation of sirtuins by vagus nerve stimulation
WO2014169145A1 (en) 2013-04-10 2014-10-16 Setpoint Medical Corporation Closed-loop vagus nerve stimulation
CN105126248B (zh) 2009-12-23 2018-06-12 赛博恩特医疗器械公司 用于治疗慢性炎症的神经刺激设备和系统
US20110274628A1 (en) 2010-05-07 2011-11-10 Borschke August J Nicotine-containing pharmaceutical compositions
WO2012007365A1 (en) * 2010-07-12 2012-01-19 F. Hoffmann-La Roche Ag 1-hydroxyimino-3-phenyl-propanes
EP2611788B1 (en) 2010-09-03 2017-04-12 University of Florida Research Foundation, Incorporated Nicotine compounds and analogs thereof, synthetic methods of making compounds, and methods of use
US12172017B2 (en) 2011-05-09 2024-12-24 Setpoint Medical Corporation Vagus nerve stimulation to treat neurodegenerative disorders
EP2707094B1 (en) 2011-05-09 2016-02-03 Setpoint Medical Corporation Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation
US9572983B2 (en) 2012-03-26 2017-02-21 Setpoint Medical Corporation Devices and methods for modulation of bone erosion
US11311725B2 (en) 2014-10-24 2022-04-26 Setpoint Medical Corporation Systems and methods for stimulating and/or monitoring loci in the brain to treat inflammation and to enhance vagus nerve stimulation
US11406833B2 (en) 2015-02-03 2022-08-09 Setpoint Medical Corporation Apparatus and method for reminding, prompting, or alerting a patient with an implanted stimulator
US10596367B2 (en) 2016-01-13 2020-03-24 Setpoint Medical Corporation Systems and methods for establishing a nerve block
CN108882885A (zh) 2016-01-20 2018-11-23 赛博恩特医疗器械公司 迷走神经刺激的控制
US10314501B2 (en) 2016-01-20 2019-06-11 Setpoint Medical Corporation Implantable microstimulators and inductive charging systems
US11471681B2 (en) 2016-01-20 2022-10-18 Setpoint Medical Corporation Batteryless implantable microstimulators
US10583304B2 (en) 2016-01-25 2020-03-10 Setpoint Medical Corporation Implantable neurostimulator having power control and thermal regulation and methods of use
WO2018064529A1 (en) 2016-09-29 2018-04-05 The Uab Research Foundation Methods and compositions for increasing mucus clearance
US11173307B2 (en) 2017-08-14 2021-11-16 Setpoint Medical Corporation Vagus nerve stimulation pre-screening test
US11660443B2 (en) 2018-04-20 2023-05-30 The Feinstein Institutes For Medical Research Methods and apparatuses for reducing bleeding via electrical trigeminal nerve stimulation
US11260229B2 (en) 2018-09-25 2022-03-01 The Feinstein Institutes For Medical Research Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation
US12343535B2 (en) 2019-04-12 2025-07-01 Setpoint Medical Corporation Vagus nerve stimulation to treat neurodegenerative disorders
AU2021207815B2 (en) 2020-01-13 2026-03-26 The Feinstein Institutes For Medical Research Treating bleeding and bleeding disorders via high intensity focused ultrasound stimulation of the spleen
US11938324B2 (en) 2020-05-21 2024-03-26 The Feinstein Institutes For Medical Research Systems and methods for vagus nerve stimulation
GB2612481A (en) * 2020-06-09 2023-05-03 Fadly Abd El Ghany Elkazaz Mohamed A novel medicament for immune modulation and treating chronic or hyper inflammation
WO2022245878A1 (en) 2021-05-17 2022-11-24 Setpoint Medical Corporation Neurostimulation parameter authentication and expiration system for neurostimulation
US20250229086A1 (en) 2022-01-20 2025-07-17 Setpoint Medical Corporation Treatment of inflammatory disorders
CN118851892A (zh) * 2023-04-20 2024-10-29 成都新睿泰康科技有限公司 一种1-(环丁亚基甲基)-2,4,5-三甲氧基苯化合物及其制备方法和应用

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3275625A (en) * 1966-09-27 Derivatives of
US3426130A (en) * 1960-12-19 1969-02-04 Squibb & Sons Inc Compositions containing a benzothiadiazinesulfonamide 1,1-dioxide
US3247213A (en) * 1961-04-12 1966-04-19 Shell Oil Co Heterocyclic nitrogen compounds
US3265573A (en) * 1962-07-27 1966-08-09 Squibb & Sons Inc Benzothiadiazinesulfonamide-1, 1-dioxide composition
US4155909A (en) * 1977-06-13 1979-05-22 Philip Morris Incorporated 2-Alkyl nicotinoids and processes for their production
US4195645A (en) * 1978-03-13 1980-04-01 Celanese Corporation Tobacco-substitute smoking material
US4965074A (en) * 1985-03-05 1990-10-23 Ciba-Geigy Corporation Method of treating memory impairment
JP2657583B2 (ja) * 1991-03-01 1997-09-24 ユニバーシテイ オブ フロリダ リサーチ ファンデーション インコーポレイテッド 神経系変性疾患の治療に対するニコチン類似体の利用
EP0659078B1 (en) * 1992-08-31 2003-01-15 University Of Florida Research Foundation, Inc. Anabaseine derivatives useful in the treatment of degenerative diseases of the nervous system
US5488049A (en) * 1993-12-10 1996-01-30 Fidia - Georgetown Institute For The Neuro-Sciences Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents

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CA2142610C (en) 2003-09-16
EP0659078A4 (en) 1996-04-24
CA2142610A1 (en) 1994-03-17
EP0659078A1 (en) 1995-06-28
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US5741802A (en) 1998-04-21
JPH08509458A (ja) 1996-10-08
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