OA11570A - 4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. - Google Patents
4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. Download PDFInfo
- Publication number
- OA11570A OA11570A OA1200000347A OA1200000347A OA11570A OA 11570 A OA11570 A OA 11570A OA 1200000347 A OA1200000347 A OA 1200000347A OA 1200000347 A OA1200000347 A OA 1200000347A OA 11570 A OA11570 A OA 11570A
- Authority
- OA
- OAPI
- Prior art keywords
- benzooxazol
- piperidin
- ethanesulfinyl
- compound
- benzyl
- Prior art date
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Classifications
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- 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
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Landscapes
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9091498P | 1998-06-26 | 1998-06-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11570A true OA11570A (en) | 2004-07-01 |
Family
ID=22224939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA1200000347A OA11570A (en) | 1998-06-26 | 1999-06-25 | 4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6284774B1 (de) |
| EP (1) | EP1089735B1 (de) |
| JP (1) | JP2002519322A (de) |
| KR (1) | KR20010053170A (de) |
| CN (1) | CN1304307A (de) |
| AP (1) | AP2000001949A0 (de) |
| AT (1) | ATE297207T1 (de) |
| AU (1) | AU769650B2 (de) |
| BG (1) | BG105082A (de) |
| BR (1) | BR9911575A (de) |
| CA (1) | CA2327888A1 (de) |
| DE (1) | DE69925730T2 (de) |
| EA (1) | EA200100058A1 (de) |
| EE (1) | EE200000778A (de) |
| ES (1) | ES2244201T3 (de) |
| HU (1) | HUP0102471A2 (de) |
| ID (1) | ID28005A (de) |
| IL (1) | IL138949A0 (de) |
| IS (1) | IS5667A (de) |
| NO (1) | NO20006482L (de) |
| NZ (1) | NZ508808A (de) |
| OA (1) | OA11570A (de) |
| PE (1) | PE20000728A1 (de) |
| PL (1) | PL345024A1 (de) |
| SK (1) | SK19512000A3 (de) |
| TR (1) | TR200003888T2 (de) |
| WO (1) | WO2000000197A1 (de) |
| ZA (1) | ZA200005848B (de) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476041B1 (en) * | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
| UA73749C2 (en) * | 1999-11-01 | 2005-09-15 | Diarylenines | |
| OA12253A (en) * | 2000-04-26 | 2006-05-11 | Warner Lambert Co | Cyclohexylamine derivative as subtype selective NMDA receptor antagonists. |
| CA2410660A1 (en) * | 2000-06-01 | 2001-12-06 | Warner-Lambert Company | Cyclohexylamine derivatives as subtype selective nmda receptor antagonists |
| AU2001269540A1 (en) | 2000-07-18 | 2002-01-30 | Sumitomo Pharmaceuticals Co. Ltd. | Serotonin reuptake inhibitors |
| IL145584A0 (en) | 2000-10-02 | 2002-06-30 | Pfizer Prod Inc | Nmda nr2b antagonists for treatment |
| HU227197B1 (en) | 2000-10-24 | 2010-10-28 | Richter Gedeon Nyrt | Nmda receptor antagonist carboxylic acid amide derivatives and pharmaceutical compositions containing them |
| EA005974B1 (ru) | 2001-02-23 | 2005-08-25 | Мерк Энд Ко., Инк. | N-замещенные неарильные гетероциклические антагонисты nmda/nr2b |
| JP2005506292A (ja) * | 2001-03-08 | 2005-03-03 | エモリー ユニバーシティ | ｐＨに依存するＮＭＤＡレセプターアンタゴニスト |
| CA2443108A1 (en) | 2001-04-03 | 2002-10-17 | Merck & Co. Inc. | N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists |
| CA2381630A1 (en) * | 2001-04-23 | 2002-10-23 | Leonard Theodore Meltzer | Method for preventing dyskinesias |
| DE60228969D1 (de) | 2001-07-24 | 2008-10-30 | Richter Gedeon Nyrt | |
| US20030211040A1 (en) | 2001-08-31 | 2003-11-13 | Paul Greengard | Phosphodiesterase activity and regulation of phosphodiesterase 1B-mediated signaling in brain |
| ES2351303T3 (es) * | 2001-12-11 | 2011-02-02 | University Of Virginia Patent Foundation | Utilización de pramipexol para el tratamiento de la esclerosis lateral amiotrófica. |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| US20040082543A1 (en) * | 2002-10-29 | 2004-04-29 | Pharmacia Corporation | Compositions of cyclooxygenase-2 selective inhibitors and NMDA receptor antagonists for the treatment or prevention of neuropathic pain |
| US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
| WO2006058236A2 (en) | 2004-11-24 | 2006-06-01 | Neuromolecular Pharmaceuticals, Inc. | Composition comprising an nmda receptor antagonist and levodopa and use thereof for treating neurological disease |
| EP2425845A1 (de) * | 2004-12-23 | 2012-03-07 | Voyager Pharmaceutical Corporation | Acetylcholinesterasehemmer und Leuprolidacetat zur Behandlung von Alzheimer-Krankheit |
| ES2334061T3 (es) * | 2005-08-15 | 2010-03-04 | University Of Virginia Patent Foundation | Neurorrestauracion con pramipexol r(+). |
| US8518926B2 (en) | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
| PL2026803T3 (pl) | 2006-05-16 | 2012-05-31 | Knopp Neurosciences Inc | Kompozycje R(+) i S(-) pramipeksolu i sposoby ich zastosowania |
| JP5379692B2 (ja) | 2006-11-09 | 2013-12-25 | プロビオドルグ エージー | 潰瘍、癌及び他の疾患の治療のためのグルタミニルシクラーゼの阻害薬としての３−ヒドロキシ−１，５−ジヒドロ−ピロール−２−オン誘導体 |
| EP2091948B1 (de) | 2006-11-30 | 2012-04-18 | Probiodrug AG | Neue inhibitoren von glutaminylcyclase |
| US8524695B2 (en) | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
| CA2679446C (en) | 2007-03-01 | 2016-05-17 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| EP2137171A4 (de) | 2007-03-14 | 2010-05-19 | Knopp Neurosciences Inc | Synthese von chiralaufgereinigten substituierten benzothiazoldiaminen |
| US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| CN103497114A (zh) | 2007-06-29 | 2014-01-08 | 埃莫里大学 | 用于神经保护的nmda受体拮抗剂 |
| DE102007047737A1 (de) | 2007-10-05 | 2009-04-30 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
| TWI410420B (zh) | 2008-02-05 | 2013-10-01 | Dainippon Sumitomo Pharma Co | 苄基哌啶化合物 |
| BRPI0910575A2 (pt) * | 2008-04-18 | 2017-06-06 | Arizona Board Of Regents A Body Corp Of The State Of Arizona Acting For And Behalf Of The Univ Of Ar | métodos para tratar degeneração macular relacionada com a idade, para limitar desenvolvimento de degeneração macular relacionada com a idade, e para identificar compostos para tratar degeneração macular relacionada com a idade, e, composição |
| US20110190356A1 (en) | 2008-08-19 | 2011-08-04 | Knopp Neurosciences Inc. | Compositions and Methods of Using (R)- Pramipexole |
| HUP0900130A3 (en) | 2009-03-03 | 2012-02-28 | Richter Gedeon Nyrt | Novel crystalline hydrate, amorphous and polymorphic forms of dihydro-benzoxazole-6-yl-acetamide derivative and processes for their preparation |
| AU2010279963A1 (en) | 2009-08-04 | 2012-02-23 | Dainippon Sumitomo Pharma Co., Ltd. | Benzyl piperidine compound |
| SG10201507362TA (en) | 2009-08-05 | 2015-10-29 | Intra Cellular Therapies Inc | Novel Regulatory Proteins And Inhibitors |
| BR112012008346B1 (pt) | 2009-09-11 | 2021-12-21 | Vivoryon Therapeutics N.V. | Derivados heterocíclicos, seu processo de preparação, e composição farmacêutica |
| US8741343B2 (en) | 2009-12-02 | 2014-06-03 | Adamas Pharmaceuticals, Inc. | Method of administering amantadine prior to a sleep period |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| DK2545047T3 (da) | 2010-03-10 | 2014-07-28 | Probiodrug Ag | Heterocycliske inhibitorer af glutaminylcyclase (QC, EC 2.3.2.5) |
| EP2560953B1 (de) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Hemmer der glutaminylzyklase |
| WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
| JP6411215B2 (ja) | 2011-11-22 | 2018-10-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 虚血傷害を治療するためのシステアミンおよび／またはシスタミン |
| US9512096B2 (en) | 2011-12-22 | 2016-12-06 | Knopp Biosciences, LLP | Synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds |
| US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
| US10154971B2 (en) | 2013-06-17 | 2018-12-18 | Adamas Pharma, Llc | Methods of administering amantadine |
| US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
| HRP20251187T1 (hr) | 2013-07-12 | 2025-11-21 | Areteia Therapeutics, Inc. | Liječenje povišenih razina eozinofila i/ili bazofila |
| US9642840B2 (en) | 2013-08-13 | 2017-05-09 | Knopp Biosciences, Llc | Compositions and methods for treating plasma cell disorders and B-cell prolymphocytic disorders |
| US9763918B2 (en) | 2013-08-13 | 2017-09-19 | Knopp Biosciences Llc | Compositions and methods for treating chronic urticaria |
| US10752588B2 (en) | 2014-12-19 | 2020-08-25 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
| US10633336B2 (en) | 2014-12-19 | 2020-04-28 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
| MX2020002078A (es) | 2017-08-24 | 2020-09-21 | Adamas Pharma Llc | Composiciones de amantadina, preparaciones de estas y métodos de uso. |
| PL3461819T3 (pl) | 2017-09-29 | 2020-11-30 | Probiodrug Ag | Inhibitory cyklazy glutaminylowej |
| US12521365B2 (en) | 2019-04-26 | 2026-01-13 | Cytosolve, Inc. | Compositions for improving brain health and memory |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE792187A (fr) * | 1971-12-03 | 1973-03-30 | Sumitomo Chemical Co | Nouveaux derives d'alkylamines |
| DE2845537A1 (de) * | 1978-10-19 | 1980-04-30 | Bayer Ag | Benzimidazolylcarbamidsaeureester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| ZA848275B (en) * | 1983-12-28 | 1985-08-28 | Degussa | New piridine-2-ethers or pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring |
| EP0488959A3 (en) | 1990-11-28 | 1992-08-05 | Sandoz Ltd. | New uses of competitive nmda receptor antagonists |
| JPH05194505A (ja) * | 1991-08-09 | 1993-08-03 | Yoshitomi Pharmaceut Ind Ltd | チオフェン化合物 |
| US5192751A (en) | 1992-07-24 | 1993-03-09 | Eli Lilly And Company | Use of competitive NMDA receptor antagonists in the treatment of urinary incontinence |
| JP2959615B2 (ja) * | 1993-06-24 | 1999-10-06 | 吉富製薬株式会社 | 縮合型チオフェン化合物およびその医薬用途 |
| EP0709384B1 (de) | 1994-10-31 | 1998-12-23 | MERCK PATENT GmbH | Benzylpiperidinderivate mit hoher Affinität zu Bindungsstellen von Aminosäure-Rezeptoren |
| EP0825984A1 (de) * | 1995-04-07 | 1998-03-04 | Novo Nordisk A/S | Neues verfahren |
| ZA9610741B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| ZA9610745B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| JP2001501628A (ja) * | 1996-10-04 | 2001-02-06 | ノボ ノルディスク アクティーゼルスカブ | Ｎ―置換化アザ複素環式化合物 |
| DE19643790A1 (de) | 1996-10-30 | 1998-05-07 | Merck Patent Gmbh | Benzoxazol-Derivat |
-
1999
- 1999-06-24 PE PE1999000567A patent/PE20000728A1/es not_active Application Discontinuation
- 1999-06-25 US US09/674,298 patent/US6284774B1/en not_active Expired - Fee Related
- 1999-06-25 ES ES99931887T patent/ES2244201T3/es not_active Expired - Lifetime
- 1999-06-25 BR BR9911575-1A patent/BR9911575A/pt not_active Application Discontinuation
- 1999-06-25 AP APAP/P/2000/001949A patent/AP2000001949A0/en unknown
- 1999-06-25 JP JP2000556782A patent/JP2002519322A/ja active Pending
- 1999-06-25 SK SK1951-2000A patent/SK19512000A3/sk unknown
- 1999-06-25 TR TR2000/03888T patent/TR200003888T2/xx unknown
- 1999-06-25 ID IDW20002514A patent/ID28005A/id unknown
- 1999-06-25 PL PL99345024A patent/PL345024A1/xx unknown
- 1999-06-25 EA EA200100058A patent/EA200100058A1/ru unknown
- 1999-06-25 EE EEP200000778A patent/EE200000778A/xx unknown
- 1999-06-25 NZ NZ508808A patent/NZ508808A/xx unknown
- 1999-06-25 AT AT99931887T patent/ATE297207T1/de not_active IP Right Cessation
- 1999-06-25 OA OA1200000347A patent/OA11570A/en unknown
- 1999-06-25 CA CA002327888A patent/CA2327888A1/en not_active Abandoned
- 1999-06-25 IL IL13894999A patent/IL138949A0/xx unknown
- 1999-06-25 DE DE69925730T patent/DE69925730T2/de not_active Expired - Fee Related
- 1999-06-25 CN CN99807087A patent/CN1304307A/zh active Pending
- 1999-06-25 WO PCT/US1999/014291 patent/WO2000000197A1/en not_active Ceased
- 1999-06-25 AU AU48303/99A patent/AU769650B2/en not_active Ceased
- 1999-06-25 HU HU0102471A patent/HUP0102471A2/hu unknown
- 1999-06-25 KR KR1020007014745A patent/KR20010053170A/ko not_active Withdrawn
- 1999-06-25 EP EP99931887A patent/EP1089735B1/de not_active Expired - Lifetime
-
2000
- 2000-10-16 IS IS5667A patent/IS5667A/is unknown
- 2000-10-19 ZA ZA200005848A patent/ZA200005848B/en unknown
- 2000-12-19 NO NO20006482A patent/NO20006482L/no not_active Application Discontinuation
- 2000-12-21 BG BG105082A patent/BG105082A/xx unknown
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| IL138949A0 (en) | 2001-11-25 |
| EE200000778A (et) | 2002-04-15 |
| AU769650B2 (en) | 2004-01-29 |
| NO20006482D0 (no) | 2000-12-19 |
| BG105082A (en) | 2001-09-28 |
| ZA200005848B (en) | 2001-12-18 |
| BR9911575A (pt) | 2001-03-20 |
| HUP0102471A2 (hu) | 2002-05-29 |
| US6284774B1 (en) | 2001-09-04 |
| PL345024A1 (en) | 2001-11-19 |
| ES2244201T3 (es) | 2005-12-01 |
| NO20006482L (no) | 2000-12-19 |
| AP2000001949A0 (en) | 2000-12-31 |
| EP1089735A4 (de) | 2002-12-18 |
| DE69925730D1 (de) | 2005-07-14 |
| EA200100058A1 (ru) | 2001-08-27 |
| PE20000728A1 (es) | 2000-08-21 |
| IS5667A (is) | 2000-10-16 |
| EP1089735A1 (de) | 2001-04-11 |
| DE69925730T2 (de) | 2006-03-23 |
| CN1304307A (zh) | 2001-07-18 |
| NZ508808A (en) | 2002-12-20 |
| JP2002519322A (ja) | 2002-07-02 |
| EP1089735B1 (de) | 2005-06-08 |
| ATE297207T1 (de) | 2005-06-15 |
| SK19512000A3 (sk) | 2001-08-06 |
| TR200003888T2 (tr) | 2001-06-21 |
| WO2000000197A1 (en) | 2000-01-06 |
| ID28005A (id) | 2001-05-03 |
| AU4830399A (en) | 2000-01-17 |
| KR20010053170A (ko) | 2001-06-25 |
| CA2327888A1 (en) | 2000-01-06 |
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