RU2595720C2 - Ингибиторы снижения когнитивных способностей - Google Patents
Ингибиторы снижения когнитивных способностей Download PDFInfo
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- RU2595720C2 RU2595720C2 RU2011145321/04A RU2011145321A RU2595720C2 RU 2595720 C2 RU2595720 C2 RU 2595720C2 RU 2011145321/04 A RU2011145321/04 A RU 2011145321/04A RU 2011145321 A RU2011145321 A RU 2011145321A RU 2595720 C2 RU2595720 C2 RU 2595720C2
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/27—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by saturated carbon chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (7)
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| US16798409P | 2009-04-09 | 2009-04-09 | |
| US61/167,984 | 2009-04-09 | ||
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| US61/308,667 | 2010-02-26 | ||
| US30909110P | 2010-03-01 | 2010-03-01 | |
| US61/309,091 | 2010-03-01 | ||
| PCT/US2010/030130 WO2010118055A1 (en) | 2009-04-09 | 2010-04-06 | Inhibitors of cognitive decline |
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| ES2545795T3 (es) | 2009-04-09 | 2015-09-15 | Cognition Therapeutics, Inc. | Inhibidores del deterioro cognitivo |
| CN102595884B (zh) | 2009-07-31 | 2014-12-03 | 考格尼申治疗股份有限公司 | 认知衰退的抑制剂 |
| BR112013019775A2 (pt) | 2011-02-02 | 2017-04-18 | Cognition Therapeutics Inc | composto, composição farmacêutica e método para tratar declínio cognitivo ou doença de alzheimer em um paciente |
| EP2747768A4 (en) * | 2011-08-25 | 2015-10-21 | Cognition Therapeutics Inc | COMPOSITIONS AND METHOD FOR THE TREATMENT OF NEURODEEGENERATIVE DISEASES |
| EP2747759A4 (en) * | 2011-08-25 | 2015-05-13 | Cognition Therapeutics Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| JP2015512383A (ja) | 2012-03-20 | 2015-04-27 | アダムド エスピー．ゼット オー．オー．Ａｄａｍｅｄ Ｓｐ．Ｚ Ｏ．Ｏ． | Ｃｎｓ疾患の処置のためのベンジルアミンのスルホンアミド誘導体 |
| PL3062791T3 (pl) | 2013-10-28 | 2020-06-15 | Drexel University | Nowoczesne terapie zaburzeń uwagi i zaburzeń poznawczych oraz otępienia związanych z zaburzeniem neurodegeneracyjnym |
| RU2692258C2 (ru) | 2014-01-31 | 2019-06-24 | Когнишн Терапьютикс, Инк. | Композиции изоиндолина и способы лечения нейродегенеративного заболевания |
| DK3634394T3 (da) | 2017-05-15 | 2026-03-02 | Cognition Therapeutics Inc | Sammensætninger til behandling af neurogenerative sygdomme |
| US12352719B2 (en) | 2019-09-20 | 2025-07-08 | KYCERA AVX Components Corporation | Somatic cell-based electrical biosensor |
| IL298323B2 (en) | 2020-05-20 | 2023-10-01 | Univ Illinois | A method for treating lysosomal storage disease using histatin peptides |
| WO2026030341A1 (en) | 2024-07-29 | 2026-02-05 | Cognition Therapeutics, Inc. | Zervimesine for treating neurodegenerative disease |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4321386A (en) * | 1981-01-28 | 1982-03-23 | Mead Johnson & Company | Quaternary piperidinium halides |
| JPS62283922A (ja) * | 1986-05-30 | 1987-12-09 | Tsumura Juntendo Inc | 血小板凝集抑制剤 |
| US4697024A (en) | 1986-11-24 | 1987-09-29 | Merrell Dow Pharmaceuticals Inc. | Medroxalol intermediates |
| JPH01180822A (ja) * | 1988-01-12 | 1989-07-18 | Dainippon Pharmaceut Co Ltd | 抗遅延型アレルギー剤 |
| CA2071897A1 (en) | 1989-12-28 | 1991-06-29 | Richard A. Glennon | Sigma receptor ligands and the use thereof |
| DE4000610A1 (de) | 1990-01-11 | 1991-07-18 | Knoll Ag | Verfahren zur herstellung von optisch aktiven 3-amino-1-arylbutanen und 3-benzylamino-1-arylbutanen |
| JP2818958B2 (ja) * | 1990-02-23 | 1998-10-30 | 塩野義製薬株式会社 | ４―（４―アルコキシフェニル）―２―ブチルアミン誘導体およびその製造法 |
| DE4142366A1 (de) | 1991-07-15 | 1993-06-24 | Thomae Gmbh Dr K | Phenylalkylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US6011068A (en) * | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| CN1192011C (zh) * | 1991-08-23 | 2005-03-09 | Nps药物有限公司 | 对钙受体具活性的芳烷基胺化合物 |
| CN1093079A (zh) * | 1993-03-30 | 1994-10-05 | 陈英俊 | 由具有愈创木酚结构之香辛类化合物及其去氢化合物衍生之肾上腺素激性乙型阻断剂 |
| ES2285707T3 (es) * | 1994-10-21 | 2007-11-16 | Nps Pharmaceuticals, Inc. | Compuestos activos frente al receptor de calcio. |
| WO1997030038A1 (en) | 1996-02-15 | 1997-08-21 | Mitsubishi Chemical Corporation | Diarylsultam derivatives |
| US6518315B1 (en) | 1997-10-21 | 2003-02-11 | The University Of Sydney | Medicinal uses of phenylaikanols and derivatives |
| JP2003505508A (ja) * | 1999-07-30 | 2003-02-12 | バーテックス ファーマシューティカルズ インコーポレイテッド | 非環式又は環式アミド誘導体 |
| WO2001030335A2 (en) | 1999-10-22 | 2001-05-03 | The Board Of Trustees Of The University Of Illinois | Pharmaceutical compositions useful in the prevention and treatment of beta-amyloid protein-induced disease |
| JP4312402B2 (ja) | 2001-07-31 | 2009-08-12 | 有限会社大長企画 | 抗うつ剤、抗更年期障害剤、抗老人性痴呆症剤、抗アルツハイマー剤 |
| US20030073681A1 (en) * | 2001-08-21 | 2003-04-17 | Hauske James R. | 2-substituted piperidines that are ligands for monoamine receptors and transporters |
| US6991814B2 (en) | 2001-12-13 | 2006-01-31 | Council Of Scientific And Industrial Research | Herbal medicaments for the treatment of neurocerebrovascular disorders |
| JP2004002517A (ja) * | 2002-05-31 | 2004-01-08 | Dae Sil Kim | 生姜成分を含む石鹸の組成物及びその製造方法 |
| DE10320560A1 (de) | 2003-05-07 | 2004-01-29 | Brosig, Stefan, Dr. | Mittel zur Bekämpfung der Alzheimer Erkrankung und/oder der Parkinson Krankheit |
| EP1644026A4 (en) | 2003-06-12 | 2007-10-24 | Ms Science Corp | SIGMA LIGANDS FOR NEURONAL REGENERATION AND FUNCTIONAL RECREATION |
| EP1794313B1 (en) | 2004-06-21 | 2013-05-15 | Proteome Sciences Plc | Screening methods using c-abl, fyn and syk in combination with tau protein |
| TW200613272A (en) | 2004-08-13 | 2006-05-01 | Astrazeneca Ab | Isoindolone compounds and their use as metabotropic glutamate receptor potentiators |
| WO2006027252A1 (en) | 2004-09-10 | 2006-03-16 | Ucb Pharma, Sa | Sigma receptor ligands |
| GB0423356D0 (en) * | 2004-10-21 | 2004-11-24 | Merck Sharp & Dohme | Therapeutic agents |
| WO2006094724A2 (en) | 2005-03-05 | 2006-09-14 | Abbott Gmbh & Co. Kg | Screening method, process for purifying of non-diffusible a-beta oligomers, selective antibodies against said non-diffusible a-beta oligomers and a process for manufacturing of said antibodies |
| KR20080041624A (ko) | 2005-06-15 | 2008-05-13 | 대릭 에스. 에치. 엘. 김 | 베타-아밀로이드 단백질-유발 안질환의 치료 방법 |
| EP1745778A3 (en) | 2005-07-20 | 2007-03-07 | Speedel Experimenta AG | Diaminoalcohols as therapeutic compounds |
| ITRM20060007A1 (it) | 2006-01-05 | 2007-07-06 | Univ Bari | Recettore sigma-2 metodo di screening di ligandi specifici e uso degli stessi in metodi diagnostici o terapeutici |
| KR20090007564A (ko) | 2006-03-17 | 2009-01-19 | 허발사이언스 싱가포르 피티이 리미티드 | 쿠르쿠마 종을 포함한 추출물 및 이를 수득하는 방법 |
| WO2007112288A2 (en) | 2006-03-23 | 2007-10-04 | Mount Sinai School Of Medicine | Cardiovascular composition and use the same for the treatment of alzheimers disease |
| US7561775B2 (en) | 2006-08-22 | 2009-07-14 | Senko Advanced Components, Inc. | Fiber optic protective shutter |
| WO2008042755A2 (en) | 2006-09-29 | 2008-04-10 | Cognition Therapeutics, Inc. | Inhibitors of cognitive decline |
| WO2008076262A2 (en) | 2006-12-15 | 2008-06-26 | Merck & Co., Inc. | Receptor for amyloid beta and uses thereof |
| CA2684920A1 (en) | 2007-05-15 | 2008-11-27 | Helicon Therapeutics, Inc. | Methods of treating cognitive disorders by inhibition of gpr12 |
| EP2206707B1 (en) * | 2007-10-24 | 2014-07-23 | Astellas Pharma Inc. | Azolecarboxamide compound or salt thereof |
| WO2009059214A1 (en) | 2007-11-02 | 2009-05-07 | The Regents Of The University Of California | Abeta-binding small molecules |
| WO2010062260A1 (en) | 2008-11-29 | 2010-06-03 | The Thailand Research Fund | Virus and target cell interaction inhibition |
| ES2545795T3 (es) | 2009-04-09 | 2015-09-15 | Cognition Therapeutics, Inc. | Inhibidores del deterioro cognitivo |
| CN102595884B (zh) | 2009-07-31 | 2014-12-03 | 考格尼申治疗股份有限公司 | 认知衰退的抑制剂 |
| WO2011106785A2 (en) | 2010-02-26 | 2011-09-01 | Cognition Therapeutics, Inc. | Methods of identifying agents effective to treat cognitive decline and diseases associated therewith |
| EP2747759A4 (en) | 2011-08-25 | 2015-05-13 | Cognition Therapeutics Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
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2016
- 2016-06-13 US US15/181,211 patent/US20160355458A1/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| [ DEDOV et al.,Gingerols:a novel class of vanilloid receptor (VR1) agonists, British Journal of Pharmacology,2002,137,pp.793-798,(pp.794,fig 1)EA 7067 B1, 30.06.2006 . . * |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2011145321A (ru) | 2013-05-20 |
| BRPI1007624A2 (pt) | 2016-07-26 |
| EP2416795A4 (en) | 2013-12-25 |
| JP2012523418A (ja) | 2012-10-04 |
| US20160355458A1 (en) | 2016-12-08 |
| IL215645A0 (en) | 2012-01-31 |
| SG176772A1 (en) | 2012-01-30 |
| CN102458435A (zh) | 2012-05-16 |
| US20120095105A1 (en) | 2012-04-19 |
| AU2015242954B2 (en) | 2016-08-25 |
| US9365491B2 (en) | 2016-06-14 |
| DK2416795T3 (en) | 2015-08-31 |
| US20140371324A1 (en) | 2014-12-18 |
| WO2010118055A1 (en) | 2010-10-14 |
| SG10201404913QA (en) | 2014-11-27 |
| EP2416795B1 (en) | 2015-06-03 |
| EP2416795A1 (en) | 2012-02-15 |
| HK1167323A1 (en) | 2013-01-04 |
| CN105968022A (zh) | 2016-09-28 |
| AU2010234518A1 (en) | 2012-02-02 |
| ES2545795T3 (es) | 2015-09-15 |
| AU2015242954A1 (en) | 2015-10-29 |
| US8765816B2 (en) | 2014-07-01 |
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