ES2703904T3 - Moduladores del receptor de NMDA y usos de los mismos - Google Patents
Moduladores del receptor de NMDA y usos de los mismos Download PDFInfo
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- ES2703904T3 ES2703904T3 ES12844456T ES12844456T ES2703904T3 ES 2703904 T3 ES2703904 T3 ES 2703904T3 ES 12844456 T ES12844456 T ES 12844456T ES 12844456 T ES12844456 T ES 12844456T ES 2703904 T3 ES2703904 T3 ES 2703904T3
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- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 title description 42
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 title description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 344
- -1 -OH Chemical group 0.000 claims abstract description 200
- 229910052736 halogen Chemical group 0.000 claims abstract description 91
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- 125000001424 substituent group Chemical group 0.000 claims abstract description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 67
- 239000001257 hydrogen Substances 0.000 claims abstract description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 150000004677 hydrates Chemical class 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 201000000980 schizophrenia Diseases 0.000 claims description 12
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- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 9
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- YWINCLIZVLSGLF-LGKHCZOZSA-N amino (2S,3R)-3-hydroxy-2-[[(2S)-1-[(2S)-1-[(2R)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]butanoate Chemical compound C(C1=CC=CC=C1)OC(N[C@@H](C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(N[C@H](C(=O)ON)[C@@H](C)O)=O)CO)=O YWINCLIZVLSGLF-LGKHCZOZSA-N 0.000 description 37
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- VBNALPYAVIAHCI-ONSCTEFMSA-N amino (2S)-3-hydroxy-2-[[(2S)-1-[(2S)-1-[(2R,3S)-3-hydroxy-2-(phenylmethoxycarbonylamino)butanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoate Chemical compound C(C1=CC=CC=C1)OC(N[C@@H](C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(N[C@H](C(=O)ON)CO)=O)[C@H](C)O)=O VBNALPYAVIAHCI-ONSCTEFMSA-N 0.000 description 33
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- 125000001072 heteroaryl group Chemical group 0.000 description 31
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 26
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 25
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- 241001465754 Metazoa Species 0.000 description 23
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 22
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 22
- 238000004296 chiral HPLC Methods 0.000 description 22
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 22
- 230000027928 long-term synaptic potentiation Effects 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 21
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 20
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
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- 238000005481 NMR spectroscopy Methods 0.000 description 19
- WVSDBKNTLMWQTQ-SNPRPXQTSA-N benzyl (2s)-2-[[(2s,3r)-3-hydroxy-1-methoxy-1-oxobutan-2-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound COC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 WVSDBKNTLMWQTQ-SNPRPXQTSA-N 0.000 description 19
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 19
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- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 17
- 125000003118 aryl group Chemical group 0.000 description 17
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- ZBDQHSHVSLIFAR-SVRRBLITSA-N (2s,3r)-3-acetyloxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(=O)O[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C ZBDQHSHVSLIFAR-SVRRBLITSA-N 0.000 description 16
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 16
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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 |
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| CA2898774C (en) | 2013-01-29 | 2021-07-13 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| US9708335B2 (en) | 2013-01-29 | 2017-07-18 | Apytinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| EA031905B1 (ru) | 2013-01-29 | 2019-03-29 | Аптиникс Инк. | Спиролактамные модуляторы рецептора nmda и их применение |
| EP3514158B1 (en) | 2013-01-29 | 2022-10-12 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CA2899010A1 (en) | 2013-01-29 | 2014-08-07 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| MX362544B (es) | 2013-03-13 | 2019-01-24 | Sage Therapeutics Inc | Esteroides neuroactivos y metodos para su uso. |
| CN104109189B (zh) * | 2013-04-18 | 2019-05-10 | 中国人民解放军军事医学科学院毒物药物研究所 | Thr-Pro-Pro-Thr四肽的液相合成方法 |
| WO2015065891A1 (en) * | 2013-10-28 | 2015-05-07 | Naurex, Inc. | Nmda receptor modulators and prodrugs, salts, and uses thereof |
| JP6628745B2 (ja) | 2014-06-18 | 2020-01-15 | セージ セラピューティクス， インコーポレイテッド | オキシステロールおよびその使用方法 |
| WO2016014982A1 (en) | 2014-07-24 | 2016-01-28 | Naurex, Inc. | N-methyl-d-aspartate receptor modulators and methods of making and using same |
| BR112017007053A2 (pt) * | 2014-10-07 | 2018-06-19 | Sage Therapeutics Inc | compostos neuroativos e métodos de utilização deste composto. |
| MA42410B1 (fr) | 2015-07-06 | 2021-04-30 | Sage Therapeutics Inc | Oxystérols et leurs méthodes d'utilisation |
| WO2017007832A1 (en) | 2015-07-06 | 2017-01-12 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| SI3812392T1 (sl) | 2015-07-06 | 2025-09-30 | Sage Therapeutics, Inc. | Oksisteroli in postopki za uporabo le-teh |
| KR20180102052A (ko) * | 2015-10-16 | 2018-09-14 | 노오쓰웨스턴 유니버시티 | 조현병, 양극성 장애, 인지 손상 및 주요 우울 장애의 치료를 위한 비전형적 항정신병약과 nmda 조절제의 약제학적 병용 |
| HUE059491T2 (hu) | 2016-04-01 | 2022-11-28 | Sage Therapeutics Inc | Oxiszterolok és azok alkalmazási eljárásai |
| WO2017193046A1 (en) | 2016-05-06 | 2017-11-09 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| MX378566B (es) | 2016-05-19 | 2025-03-11 | Aptinyx Inc | Moduladores del receptor espiro-lactama n-metil-d-aspartato y usos de los mismos. |
| PT3481846T (pt) | 2016-07-07 | 2021-08-13 | Sage Therapeutics Inc | 24-hidroxiesteroides 11-substituídos para utilização no tratamento de afeções relacionadas com nmda |
| KR102462288B1 (ko) | 2016-08-01 | 2022-11-01 | 앱티닉스 인크. | 스피로-락탐 및 비스-스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| EP3490990B1 (en) | 2016-08-01 | 2023-12-06 | Tenacia Biotechnology (Hong Kong) Co., Limited | Spiro-lactam nmda modulators and methods of using same |
| EP3490974B1 (en) | 2016-08-01 | 2023-12-06 | Tenacia Biotechnology (Hong Kong) Co., Limited | Spiro-lactam nmda receptor modulators and uses thereof |
| JP7032378B2 (ja) | 2016-08-01 | 2022-03-08 | 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ｎｍｄａ受容体修飾因子及びその使用 |
| JP2019527233A (ja) | 2016-08-01 | 2019-09-26 | 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ｎｍｄａ受容体修飾因子及びその使用 |
| EP3519422B1 (en) | 2016-09-30 | 2022-08-31 | Sage Therapeutics, Inc. | C7 substituted oxysterols and these compounds for use as nmda modulators |
| EP4105223B1 (en) | 2016-10-18 | 2025-04-30 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| MA46566A (fr) | 2016-10-18 | 2019-08-28 | Sage Therapeutics Inc | Oxystérols et leurs procédés d'utilisation |
| CN108148113A (zh) * | 2016-12-06 | 2018-06-12 | 深圳先进技术研究院 | 一种nmda受体调控剂四肽衍生物的固相合成方法 |
| CN107474107B (zh) * | 2017-05-18 | 2023-01-17 | 江苏恩华药业股份有限公司 | Glyx-13的制备方法及用于制备glyx-13的化合物 |
| FR3067028B1 (fr) * | 2017-06-06 | 2019-07-12 | Adpuerivitam | Modulateurs de recepteurs nmda, compositions les comprenant et utilisation de ces composes dans le traitement de maladies impliquant le systeme nerveux central |
| WO2019023479A1 (en) * | 2017-07-28 | 2019-01-31 | Naurex Inc. | METHOD AND INTERMEDIATES FOR THE SYNTHESIS OF PEPTIDE COMPOUNDS |
| AU2019215058A1 (en) | 2018-01-31 | 2020-09-17 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| CN110003309B (zh) * | 2019-04-09 | 2021-09-10 | 北京广为医药科技有限公司 | 调节nmda受体活性的化合物、其药物组合物及用途 |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4683221A (en) * | 1986-01-09 | 1987-07-28 | Scripps Clinic And Research Foundation | Lymphocyte-activating polypeptides |
| 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 |
| JP3318622B2 (ja) * | 1992-05-27 | 2002-08-26 | 独立行政法人産業技術総合研究所 | プロリルエンドペプチダーゼ阻害剤 |
| 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) |
| 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 |
| EP0914333B1 (en) | 1996-06-07 | 2004-11-24 | AstraZeneca AB | Peptide derivatives |
| WO1998005782A1 (en) | 1996-08-02 | 1998-02-12 | 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 |
| EP0990051A1 (en) * | 1997-07-07 | 2000-04-05 | Florida State University | Identification of molecular targets |
| US6897028B1 (en) * | 1997-07-07 | 2005-05-24 | Florida State University | Identification of molecular targets |
| AU1585999A (en) | 1997-11-12 | 1999-05-31 | 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 |
| US6902886B1 (en) * | 1998-11-06 | 2005-06-07 | The Research Foundation Of State University Of New York | Genetic assay for protein nuclear transport |
| WO2000028090A2 (en) | 1998-11-12 | 2000-05-18 | Nyxis, 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 |
| WO2001036685A2 (en) | 1999-11-17 | 2001-05-25 | Nyxis Neurotherapies, Inc. | Differential gene expression in cancer |
| JP2003521247A (ja) | 2000-02-01 | 2003-07-15 | エージーワイ セラピューティクス インコーポレーテッド | Ｎｍｄａ受容体のプロテインチロシンホスファターゼとの相互作用 |
| WO2001096606A2 (en) | 2000-06-14 | 2001-12-20 | 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 |
| 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 |
| US20020142287A1 (en) | 2000-12-14 | 2002-10-03 | Hirotaka Yamamoto | High throughput assay to detect inhibitors of the map kinase pathway |
| WO2002072005A2 (en) | 2001-03-07 | 2002-09-19 | University Of Utah Research Foundation | Linear y-carboxyglutamate rich conotoxins |
| AU2002255705A1 (en) | 2001-03-12 | 2002-09-24 | Nyxis Neurotherapies, Inc | Neuroactive peptides for prevention and/or treatment of hypoxia and neuropathic pain |
| CA2449168A1 (en) * | 2001-05-31 | 2002-12-05 | The Trustees Of Princeton University | Iap binding peptides and assays for identifying compounds that bind iap |
| WO2003010540A1 (en) | 2001-07-25 | 2003-02-06 | Nyxis Neurotherapies, Inc. | Method of identifying nmda-related agent |
| US7273889B2 (en) | 2002-09-25 | 2007-09-25 | Innovative Drug Delivery Systems, Inc. | NMDA receptor antagonist formulation with reduced neurotoxicity |
| US7544478B2 (en) | 2003-08-08 | 2009-06-09 | The Burnham Institute | Method for screening for compounds that modulate P16 mediated regulation of NMDA receptors |
| US7662856B2 (en) | 2003-08-29 | 2010-02-16 | The University Of Houston System | Compositions having antimycrobial activity including a hydroxamate or a hydroxamate and a hydroxlyamine |
| US20050096311A1 (en) | 2003-10-30 | 2005-05-05 | Cns Response | Compositions and methods for treatment of nervous system disorders |
| EP1945691A2 (en) | 2005-08-26 | 2008-07-23 | Wisconsin Alumni Research Foundation | Poly-beta-peptides from functionalized beta-lactam monomers and antibacterial compositions containing same |
| US8507439B2 (en) * | 2005-08-29 | 2013-08-13 | Angela Shashoua | Neuroprotective and neurorestorative method and compositions |
| US20070208001A1 (en) | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| JP2010503677A (ja) | 2006-09-15 | 2010-02-04 | シェーリング コーポレイション | 脂質代謝の障害を治療するためのアゼチジノン誘導体 |
| 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 |
| CN101317844B (zh) * | 2007-06-08 | 2010-11-17 | 章劲夫 | 化合物(+)-5-甲基-10，11-二氢-5H-二苯并〔a，d〕环庚烯-5，10-亚胺在制备避孕药物中的应用 |
| 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 |
| CA2732091A1 (en) | 2008-08-07 | 2010-02-11 | F. Hoffmann-La Roche Ag | Process for the preparation of a macrocycle |
| CA2740628C (en) | 2008-09-18 | 2018-05-01 | Naurex, Inc. | Nmda receptor modulators and uses thereof |
| WO2010065709A2 (en) | 2008-12-03 | 2010-06-10 | Amin Khan | Hydroxamic acid derivatives, preparation and therapeutic uses thereof |
| TW201028171A (en) * | 2008-12-15 | 2010-08-01 | Calpis Co Ltd | Peptides for inhibiting skin aging |
| US20120178695A1 (en) | 2009-07-02 | 2012-07-12 | Joseph Moskal | Methods of treating neuropathic pain |
| EP3488856A1 (en) | 2009-10-05 | 2019-05-29 | Northwestern University | Methods of treating depression and other related diseases |
| US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
| US9101612B2 (en) | 2010-02-11 | 2015-08-11 | Northwestern University | Secondary structure stabilized NMDA receptor modulators and uses thereof |
| KR101692275B1 (ko) | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| KR20200043534A (ko) | 2011-04-27 | 2020-04-27 | 노오쓰웨스턴 유니버시티 | 알츠하이머병, 헌팅톤병, 자폐증 또는 기타 장애의 치료 방법 |
| US8795919B2 (en) | 2011-11-29 | 2014-08-05 | Societe BIC & Sanyo Electric Co., Ltd. | Fuel cell layer |
-
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- 2011-02-11 KR KR1020127023731A patent/KR101692275B1/ko not_active Expired - Fee Related
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