RU2515615C2 - Модуляторы нмда-рецептора и их применения - Google Patents
Модуляторы нмда-рецептора и их применения Download PDFInfo
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- RU2515615C2 RU2515615C2 RU2011114982/04A RU2011114982A RU2515615C2 RU 2515615 C2 RU2515615 C2 RU 2515615C2 RU 2011114982/04 A RU2011114982/04 A RU 2011114982/04A RU 2011114982 A RU2011114982 A RU 2011114982A RU 2515615 C2 RU2515615 C2 RU 2515615C2
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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| US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
| KR101692275B1 (ko) * | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| US10583138B2 (en) | 2012-07-12 | 2020-03-10 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| CN103974712A (zh) * | 2011-04-27 | 2014-08-06 | 西北大学 | 治疗阿尔茨海默氏症、亨廷顿氏症、孤独症和其他障碍的方法 |
| US9828384B2 (en) * | 2013-01-29 | 2017-11-28 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| KR102280616B1 (ko) * | 2013-01-29 | 2021-07-21 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| KR20150110784A (ko) | 2013-01-29 | 2015-10-02 | 노렉스, 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
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| JP6419087B2 (ja) * | 2013-01-29 | 2018-11-07 | アプティニックス インコーポレイテッド | スピロラクタム系ｎｍｄａ受容体モジュレーターおよびその使用 |
| EP3564256A1 (en) * | 2013-10-28 | 2019-11-06 | Naurex Inc. | Nmda receptor modulators |
| EP3171941B1 (en) * | 2014-07-24 | 2021-03-24 | Naurex Inc. | N-methyl-d-aspartate receptor modulators and methods of making and using same |
| CN104546809B (zh) * | 2015-01-13 | 2018-08-24 | 西安力邦制药有限公司 | 3,3’,5,5’-四异丙基-4,4’-二联苯酚在预防及治疗缺血性脑卒中中的应用 |
| US10583171B2 (en) | 2015-11-30 | 2020-03-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | NMDAR antagonists for the treatment of diseases associated with angiogenesis |
| JP6823083B2 (ja) * | 2016-05-19 | 2021-01-27 | アプティニックス インコーポレイテッド | スピロラクタム系ｎｍｄａ受容体モジュレーターおよびその使用 |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| SG11201900558RA (en) | 2016-08-01 | 2019-02-27 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
| EA201990425A1 (ru) | 2016-08-01 | 2019-08-30 | Аптиникс Инк. | Спиролактамовые и бис-спиролактамовые модуляторы nmda-рецептора и их применение |
| BR112019001768A2 (pt) | 2016-08-01 | 2019-06-11 | Aptinyx Inc | moduladores do receptor de spiro-lactamas nmda e usos dos mesmos |
| CN109843889B (zh) | 2016-08-01 | 2022-03-15 | 阿普廷伊克斯股份有限公司 | 螺-内酰胺nmda调节剂和使用其的方法 |
| KR102465757B1 (ko) | 2016-08-01 | 2022-11-09 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| BR112019026449A2 (pt) | 2017-06-12 | 2020-08-11 | Glytech Llc. | composição e método para tratamento de depressão e psicose em humanos |
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| PE20210455A1 (es) | 2018-01-31 | 2021-03-08 | Aptinyx Inc | Moduladores del receptor nmda espiro-lactama y usos de los mismos |
| BR112020015666A2 (pt) * | 2018-01-31 | 2021-02-23 | Aptinyx Inc. | moduladores de espiro-lactamas de receptores nmda e usos dos mesmos |
| US20220267341A1 (en) * | 2019-06-24 | 2022-08-25 | Naurex Inc. | Solid forms of tert-butyl (s)-2((2s,3r)-1-amino-3-hydroxy-1-oxobu tan-2-yl)-1-oxo-2, 5-diazaspiro [3.4] octan e-5-carboxylate and methods of preparing them |
| EP4484431A3 (en) | 2019-06-24 | 2025-03-26 | Naurex Inc. | Processes and intermediates for producing diazaspiro lactam compounds |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2039035C1 (ru) * | 1991-01-22 | 1995-07-09 | Американ Хоум Продактс Корпорейшн | Производные {[2- (амино -3,4- диоксо -1- циклобутен -1-ил) амино] алкиловых}кислот |
| US6541453B2 (en) * | 1996-06-07 | 2003-04-01 | Syngenta Limited | Peptide derivatives |
Family Cites Families (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0180398A1 (en) | 1984-10-26 | 1986-05-07 | The Regents Of The University Of California | Synthesis of beta-lactam |
| CA1305177C (en) | 1987-06-30 | 1992-07-14 | Yasufumi Ohfune | Carboxycyclopropylglycine and process for producing the same |
| US4904681A (en) | 1987-12-01 | 1990-02-27 | G. D. Searle & Co. | D-cycloserine and its prodrugs as cognitive enhancers |
| EP0360390A1 (en) * | 1988-07-25 | 1990-03-28 | Glaxo Group Limited | Spirolactam derivatives |
| US5061721A (en) | 1989-03-15 | 1991-10-29 | G. D. Searle & Co. | Composition containing d-cycloserine and d-alanine for memory and learning enhancement or treatment of a cognitive or psychotic disorder |
| US5086072A (en) | 1990-06-18 | 1992-02-04 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of mood disorders with functional antagonists of the glycine/nmda receptor complex |
| US5350769A (en) | 1990-10-30 | 1994-09-27 | Ss Pharmaceutical Co., Ltd. | Antiinflammatory gel preparation |
| FR2692268B1 (fr) | 1992-06-15 | 1994-08-19 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activité de récepteur NMDA, acides nucléiques codant pour ces polypeptides et utilisations. |
| SE9301667D0 (sv) | 1993-05-14 | 1993-05-14 | Kabi Pharmacia Ab | New use |
| US5523323A (en) | 1993-09-14 | 1996-06-04 | Maccecchini; Maria-Luisa | Use of partial agonists of the NMDA receptor to reduce opiate induced tolerance and dependence |
| US5605911A (en) | 1995-01-31 | 1997-02-25 | Washington University | Use of alpha-2 adrenergic drugs to prevent adverse effects of NMDA receptor hypofunction (NRH) |
| US6335358B1 (en) | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| US5741778A (en) | 1996-03-19 | 1998-04-21 | Amgen Inc. | Method for treating Huntington's disease using glial cell line-derived neurotrophic factor (GDNF) protein product |
| US5763393A (en) | 1996-05-17 | 1998-06-09 | Neurotherapeutics L.P. | Neuroactive peptides |
| AU3972797A (en) * | 1996-08-02 | 1998-02-25 | Zymogenetics Inc. | Testis-specific insulin homolog polypeptides |
| US5902815A (en) | 1996-09-03 | 1999-05-11 | Washington University | Use of 5HT-2A serotonin agonists to prevent adverse effects of NMDA receptor hypofunction |
| JP3955345B2 (ja) | 1996-09-27 | 2007-08-08 | サントリー株式会社 | 新規アミノ酸ダイジハーベイン |
| WO1999024584A1 (en) | 1997-11-12 | 1999-05-20 | Neurotherapeutics | Methods for the detection and treatment of disease using a glycosyltransferase |
| US5952389A (en) | 1998-01-13 | 1999-09-14 | Synchroneuron | Methods of treating tardive dyskinesia and other movement disorders |
| US6007841A (en) | 1998-03-13 | 1999-12-28 | Algos Pharmaceutical Corporation | Analgesic composition and method for treating pain |
| US6274314B1 (en) | 1998-04-02 | 2001-08-14 | Nyxis Neurotherapies, Inc. | Diagnostic assay for the modified nucleosides pseudouridine, 7-methyladenosine, or 1-methyladenosine |
| US6197820B1 (en) | 1998-04-06 | 2001-03-06 | Uab Research Foundation | Use of phenylglycine derivatives to decrease neuronal death caused by brain tumors and brain lesions |
| US6025471A (en) * | 1998-06-03 | 2000-02-15 | Deghenghi; Romano | Diazaspiro, azepino and azabicyclo therapeutic peptides |
| US6194158B1 (en) | 1998-11-12 | 2001-02-27 | Nyxis Neurotherapies, Inc. | Diagnostic assay for cancer |
| US20030064921A1 (en) * | 1999-10-27 | 2003-04-03 | The Regents Of The University Of California | Methods and compounds for modulating melanocortin receptor ligand binding and activity |
| AU1922301A (en) | 1999-11-17 | 2001-05-30 | Nyxis Neurotherapies, Inc. | Differential gene expression in cancer |
| AU782678B2 (en) | 2000-02-01 | 2005-08-18 | Agy Therapeutics, Inc. | Interaction of NMDA receptor with protein tyrosine phosphatase |
| AU2001268467A1 (en) | 2000-06-14 | 2001-12-24 | Nyxis Neurotherapies, Inc. | Identification of genes and compounds for treatment of cancer |
| EP1296999A2 (en) | 2000-06-22 | 2003-04-02 | NYXIS NeuroTherapies, Inc. | Neuroactive peptides for treatment of hypoxia and related conditions |
| GB0018272D0 (en) | 2000-07-25 | 2000-09-13 | Vernalis Research Limited | Chemical compounds IV |
| IL145209A0 (en) | 2000-09-06 | 2002-06-30 | Pfizer Prod Inc | Pharmaceutical combinations for the treatment of stroke and traumatic brain injury |
| EP1186303A3 (en) | 2000-09-06 | 2003-12-10 | Pfizer Products Inc. | Pharmaceutical combinations, for the treatment of stroke and traumatic brain injury, containing a neutrophil inhibiting factor and an selective NMDA-NR2B receptor antagonist |
| UA73619C2 (en) | 2000-12-13 | 2005-08-15 | Pfizer Prod Inc | Stable pharmaceutical compositions of nmda receptor agonist (variants) and method of treatment |
| AU2002236608A1 (en) | 2000-12-14 | 2002-06-24 | Nyxis Neurotherapies, Inc. | High throughput assay to detect inhibitors of the map kinase pathway |
| AU2002248553A1 (en) | 2001-03-07 | 2002-09-24 | Cognetix, Inc | Linear y-carboxyglutamate rich conotoxins |
| WO2002072609A2 (en) | 2001-03-12 | 2002-09-19 | Nyxis Neurotherapies, Inc | Neuroactive peptides for prevention and/or treatment of hypoxia and neuropathic pain |
| WO2003010540A1 (en) | 2001-07-25 | 2003-02-06 | Nyxis Neurotherapies, Inc. | Method of identifying nmda-related agent |
| CA2491506C (en) | 2002-07-05 | 2011-04-26 | Targacept, Inc. | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| US7273889B2 (en) | 2002-09-25 | 2007-09-25 | Innovative Drug Delivery Systems, Inc. | NMDA receptor antagonist formulation with reduced neurotoxicity |
| WO2005014797A2 (en) | 2003-08-08 | 2005-02-17 | The Burnham Institute | P16 mediated regulation of nmda receptors |
| WO2005020973A2 (en) | 2003-08-29 | 2005-03-10 | The University Of Houston System | Compositions having antimycrobial activity including a hydroxamate or a hydroxamate and a hydroxylamine |
| GB0323204D0 (en) | 2003-10-03 | 2003-11-05 | Novartis Ag | Organic compounds |
| US20050096311A1 (en) | 2003-10-30 | 2005-05-05 | Cns Response | Compositions and methods for treatment of nervous system disorders |
| WO2006034196A1 (en) | 2004-09-17 | 2006-03-30 | Lifelike Biomatic Inc. | Compositions for enhancing memory and methods therefor |
| WO2006102644A2 (en) | 2005-03-24 | 2006-09-28 | Emory University | Methods for the treatment of central nervous system injury via a tapered administration of progesterone |
| AU2006282942B2 (en) | 2005-08-26 | 2012-07-26 | Wisconsin Alumni Research Foundation | Poly-beta-peptides from functionalized beta-lactam monomers and antibacterial compositions containing same |
| AR059224A1 (es) | 2006-01-31 | 2008-03-19 | Jerini Ag | Compuestos para la inhibicion de integrinas y uso de estas |
| WO2007103719A2 (en) | 2006-03-03 | 2007-09-13 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| CN100358908C (zh) * | 2006-03-16 | 2008-01-02 | 中国科学院上海有机化学研究所 | Nmda受体拮抗剂中间体、合成方法和用途 |
| WO2008033464A2 (en) | 2006-09-15 | 2008-03-20 | Schering Corporation | Azetidinone derivatives for the treatment of disorders of the lipid metabolism |
| JP2008188285A (ja) | 2007-02-06 | 2008-08-21 | Bridgestone Corp | バックパッド及び車両用シート |
| CN101066945B (zh) | 2007-05-25 | 2010-05-19 | 中国科学院上海有机化学研究所 | 一种合成3-位取代内酰胺类化合物的方法 |
| CN101125817B (zh) | 2007-08-03 | 2011-09-14 | 中国科学院上海有机化学研究所 | 一种合成高对映选择性醛基取代小环胺类化合物和光学活性3-位取代内酰胺类化合物的方法 |
| WO2009039390A2 (en) | 2007-09-20 | 2009-03-26 | Naurex Inc. | The development of glycobiology-based therapeutics for the treatment of brain tumors |
| US9783851B2 (en) | 2008-02-20 | 2017-10-10 | The Children's Hospital Of Philadelphia | Genetic alterations associated with autism and the autistic phenotype and methods of use thereof for the diagnosis and treatment of autism |
| US20110136862A1 (en) | 2008-06-27 | 2011-06-09 | Neurosearch A/S | Novel tetramethyl substituted piperidine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| KR101647520B1 (ko) | 2008-08-07 | 2016-08-10 | 에프. 호프만-라 로슈 아게 | 거대환식 화합물의 제조 방법 |
| GB0814991D0 (en) | 2008-08-15 | 2008-09-24 | Glaxo Group Ltd | Compounds |
| MX2011003015A (es) | 2008-09-18 | 2011-11-18 | Univ Northwestern | Moduladores del receptor de n-metil-d-aspartato, y usos de los mismos. |
| WO2010065709A2 (en) | 2008-12-03 | 2010-06-10 | Amin Khan | Hydroxamic acid derivatives, preparation and therapeutic uses thereof |
| DE102009001460B4 (de) | 2009-03-11 | 2010-12-02 | Zf Friedrichshafen Ag | Ölbehälter |
| WO2011003064A2 (en) | 2009-07-02 | 2011-01-06 | Naurex, Inc. | Methods of treating neuropathic pain |
| DK2485751T3 (da) | 2009-10-05 | 2014-08-18 | Univ Northwestern | GLYX-13 til anvendelse i en fremgangsmåde til behandling af upåvirkelig depression |
| US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
| MX2012009388A (es) | 2010-02-11 | 2012-10-01 | Univ Northwestern | Moduladores del receptor de n-metil-d-aspartato estabilizado de estructura secundaria y sus usos. |
| KR101692275B1 (ko) | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| TW201245116A (en) | 2010-08-12 | 2012-11-16 | Tetraphase Pharmaceuticals Inc | Tetracycline analogs |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| CN103974712A (zh) | 2011-04-27 | 2014-08-06 | 西北大学 | 治疗阿尔茨海默氏症、亨廷顿氏症、孤独症和其他障碍的方法 |
| JP6388536B2 (ja) | 2011-06-27 | 2018-09-12 | コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． | 超音波振動子アセンブリ及びその製造方法 |
| BR112014001768B1 (pt) | 2011-07-27 | 2019-02-05 | Astrazeneca Ab | composto n-(2-{2-dimetilaminoetil-metilamino}-4-metóxi-5-{[4-(1-metilindol-3-il) pirimidin-2-il]amino}fenil) prop-2-enamida ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica e uso do dito composto |
| JP6419087B2 (ja) | 2013-01-29 | 2018-11-07 | アプティニックス インコーポレイテッド | スピロラクタム系ｎｍｄａ受容体モジュレーターおよびその使用 |
| US9828384B2 (en) | 2013-01-29 | 2017-11-28 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| KR102280616B1 (ko) | 2013-01-29 | 2021-07-21 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| KR20150110784A (ko) | 2013-01-29 | 2015-10-02 | 노렉스, 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| AU2014212490A1 (en) | 2013-01-29 | 2015-07-30 | Aptinyx, Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| JP6823083B2 (ja) | 2016-05-19 | 2021-01-27 | アプティニックス インコーポレイテッド | スピロラクタム系ｎｍｄａ受容体モジュレーターおよびその使用 |
| EA201990425A1 (ru) | 2016-08-01 | 2019-08-30 | Аптиникс Инк. | Спиролактамовые и бис-спиролактамовые модуляторы nmda-рецептора и их применение |
| KR102465757B1 (ko) | 2016-08-01 | 2022-11-09 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| BR112019001768A2 (pt) | 2016-08-01 | 2019-06-11 | Aptinyx Inc | moduladores do receptor de spiro-lactamas nmda e usos dos mesmos |
| CN109843889B (zh) | 2016-08-01 | 2022-03-15 | 阿普廷伊克斯股份有限公司 | 螺-内酰胺nmda调节剂和使用其的方法 |
| SG11201900558RA (en) | 2016-08-01 | 2019-02-27 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
-
2009
- 2009-09-18 MX MX2011003015A patent/MX2011003015A/es active IP Right Grant
- 2009-09-18 EP EP09815233.3A patent/EP2331571B1/en active Active
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- 2020-12-04 US US17/111,657 patent/US20210332061A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2039035C1 (ru) * | 1991-01-22 | 1995-07-09 | Американ Хоум Продактс Корпорейшн | Производные {[2- (амино -3,4- диоксо -1- циклобутен -1-ил) амино] алкиловых}кислот |
| US6541453B2 (en) * | 1996-06-07 | 2003-04-01 | Syngenta Limited | Peptide derivatives |
Non-Patent Citations (1)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2566821C2 (ru) * | 2010-02-11 | 2015-10-27 | Нортвестерн Юниверсити | Модулятор nmda-рецептора со стабилизированной вторичной структурой и его применение |
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| IL211802A (en) | 2017-03-30 |
| BRPI0918868B1 (pt) | 2020-07-21 |
| US9512133B2 (en) | 2016-12-06 |
| AU2009293164B2 (en) | 2015-07-09 |
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| US20110306586A1 (en) | 2011-12-15 |
| EP2331571B1 (en) | 2015-08-26 |
| JP5702288B2 (ja) | 2015-04-15 |
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