JP2014530881A5 - - Google Patents
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- Publication number
- JP2014530881A5 JP2014530881A5 JP2014537360A JP2014537360A JP2014530881A5 JP 2014530881 A5 JP2014530881 A5 JP 2014530881A5 JP 2014537360 A JP2014537360 A JP 2014537360A JP 2014537360 A JP2014537360 A JP 2014537360A JP 2014530881 A5 JP2014530881 A5 JP 2014530881A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- optionally substituted
- necrostatin
- halogen
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 125000000217 alkyl group Chemical group 0.000 claims 41
- 229910052736 halogen Inorganic materials 0.000 claims 18
- 150000002367 halogens Chemical class 0.000 claims 18
- 229910052739 hydrogen Inorganic materials 0.000 claims 18
- 239000001257 hydrogen Substances 0.000 claims 18
- 239000003814 drug Substances 0.000 claims 16
- 150000003839 salts Chemical class 0.000 claims 15
- TXUWMXQFNYDOEZ-UHFFFAOYSA-N 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone Chemical group O=C1N(C)C(=S)NC1CC1=CNC2=CC=CC=C12 TXUWMXQFNYDOEZ-UHFFFAOYSA-N 0.000 claims 13
- 150000002148 esters Chemical class 0.000 claims 13
- 229940002612 prodrug Drugs 0.000 claims 13
- 239000000651 prodrug Substances 0.000 claims 13
- 150000002431 hydrogen Chemical class 0.000 claims 12
- 125000003545 alkoxy group Chemical group 0.000 claims 11
- 229940088872 Apoptosis inhibitor Drugs 0.000 claims 10
- 239000000158 apoptosis inhibitor Substances 0.000 claims 10
- 210000002569 neuron Anatomy 0.000 claims 9
- 125000003107 substituted aryl group Chemical group 0.000 claims 9
- 125000001072 heteroaryl group Chemical group 0.000 claims 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 7
- 125000000623 heterocyclic group Chemical group 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- 210000003169 central nervous system Anatomy 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- 229940127255 pan-caspase inhibitor Drugs 0.000 claims 5
- 125000004475 heteroaralkyl group Chemical group 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 claims 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 3
- 102100022501 Receptor-interacting serine/threonine-protein kinase 1 Human genes 0.000 claims 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 3
- 125000002252 acyl group Chemical group 0.000 claims 3
- 230000003376 axonal effect Effects 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 229950000234 emricasan Drugs 0.000 claims 3
- 230000017074 necrotic cell death Effects 0.000 claims 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims 3
- 230000008929 regeneration Effects 0.000 claims 3
- 238000011069 regeneration method Methods 0.000 claims 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- 125000004442 acylamino group Chemical group 0.000 claims 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 2
- 229940043355 kinase inhibitor Drugs 0.000 claims 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 2
- 230000001737 promoting effect Effects 0.000 claims 2
- WIKGAEMMNQTUGL-SNVBAGLBSA-N (5r)-5-[(7-chloro-1h-indol-3-yl)methyl]-3-methylimidazolidine-2,4-dione Chemical compound O=C1N(C)C(=O)N[C@@H]1CC1=CNC2=C(Cl)C=CC=C12 WIKGAEMMNQTUGL-SNVBAGLBSA-N 0.000 claims 1
- SMJGLNVGTJLIRV-KBEFMPHXSA-N (5z)-5-[[5-(4-fluorophenyl)-1h-pyrazol-4-yl]methylidene]-2-imino-3-(1,3-thiazol-2-yl)-1,3-thiazolidin-4-one Chemical compound C1=CC(F)=CC=C1C1=C(\C=C/2C(N(C(=N)S\2)C=2SC=CN=2)=O)C=NN1 SMJGLNVGTJLIRV-KBEFMPHXSA-N 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 1
- QXGBVUBUQAGSCW-RXVVDRJESA-N 1-[(3r,3ar)-8-methoxy-3-(4-methoxyphenyl)-3,3a,4,5-tetrahydrobenzo[g]indazol-2-yl]ethanone Chemical compound C1=CC(OC)=CC=C1[C@@H]1N(C(C)=O)N=C2C3=CC(OC)=CC=C3CC[C@@H]21 QXGBVUBUQAGSCW-RXVVDRJESA-N 0.000 claims 1
- VGONMECBFMCKBS-UHFFFAOYSA-N 2-[[3-(4-methoxyphenyl)-4-oxo-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-2-yl]sulfanyl]acetonitrile Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(C=2CCCCC=2S2)=C2N=C1SCC#N VGONMECBFMCKBS-UHFFFAOYSA-N 0.000 claims 1
- 101710138589 Receptor-interacting serine/threonine-protein kinase 1 Proteins 0.000 claims 1
- 102100033729 Receptor-interacting serine/threonine-protein kinase 3 Human genes 0.000 claims 1
- 101710138585 Receptor-interacting serine/threonine-protein kinase 3 Proteins 0.000 claims 1
- MIFGOLAMNLSLGH-QOKNQOGYSA-N Z-Val-Ala-Asp(OMe)-CH2F Chemical group COC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 MIFGOLAMNLSLGH-QOKNQOGYSA-N 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000005518 carboxamido group Chemical group 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 210000003618 cortical neuron Anatomy 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 230000006870 function Effects 0.000 claims 1
- 125000004404 heteroalkyl group Chemical group 0.000 claims 1
- 125000005549 heteroarylene group Chemical group 0.000 claims 1
- 210000004295 hippocampal neuron Anatomy 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 230000014759 maintenance of location Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 210000001259 mesencephalon Anatomy 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 210000002161 motor neuron Anatomy 0.000 claims 1
- -1 necrostatin-4 Chemical compound 0.000 claims 1
- 230000003955 neuronal function Effects 0.000 claims 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 1
- 210000001176 projection neuron Anatomy 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 210000001044 sensory neuron Anatomy 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 0 C*(C)c1ccc(C)[n]1*=C Chemical compound C*(C)c1ccc(C)[n]1*=C 0.000 description 3
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161550191P | 2011-10-21 | 2011-10-21 | |
| US61/550,191 | 2011-10-21 | ||
| PCT/US2012/061324 WO2013059791A2 (en) | 2011-10-21 | 2012-10-22 | Methods and compositions for promoting axon regeneration and nerve function |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017228601A Division JP6560325B2 (ja) | 2011-10-21 | 2017-11-29 | 軸索再生および神経機能を促進するための方法および組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014530881A JP2014530881A (ja) | 2014-11-20 |
| JP2014530881A5 true JP2014530881A5 (enExample) | 2015-12-10 |
| JP6254090B2 JP6254090B2 (ja) | 2017-12-27 |
Family
ID=47116494
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014537360A Active JP6254090B2 (ja) | 2011-10-21 | 2012-10-22 | 軸索再生および神経機能を促進するための方法および組成物 |
| JP2017228601A Expired - Fee Related JP6560325B2 (ja) | 2011-10-21 | 2017-11-29 | 軸索再生および神経機能を促進するための方法および組成物 |
| JP2019132740A Expired - Fee Related JP6861764B2 (ja) | 2011-10-21 | 2019-07-18 | 軸索再生および神経機能を促進するための方法および組成物 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017228601A Expired - Fee Related JP6560325B2 (ja) | 2011-10-21 | 2017-11-29 | 軸索再生および神経機能を促進するための方法および組成物 |
| JP2019132740A Expired - Fee Related JP6861764B2 (ja) | 2011-10-21 | 2019-07-18 | 軸索再生および神経機能を促進するための方法および組成物 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US20140357570A1 (enExample) |
| EP (1) | EP2773341A2 (enExample) |
| JP (3) | JP6254090B2 (enExample) |
| CA (1) | CA2888805C (enExample) |
| HK (1) | HK1203044A1 (enExample) |
| WO (1) | WO2013059791A2 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130137642A1 (en) | 2010-04-23 | 2013-05-30 | Demetrios Vavvas | Methods and compositions for preserving photoreceptor and retinal pigment epithelial cells |
| US20140024598A1 (en) | 2010-11-01 | 2014-01-23 | Demetrios Vavvas | Methods and compositions for preserving retinal ganglion cells |
| EP2773341A2 (en) | 2011-10-21 | 2014-09-10 | Massachusetts Eye & Ear Infirmary | Compositions comprising necrosis inhibitors, such as necrostatins, alone or in combination, for promoting axon regeneration and nerve function, thereby treating cns disorders |
| TWI648274B (zh) | 2013-02-15 | 2019-01-21 | 英商葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之雜環醯胺類 （二） |
| CL2013003785A1 (es) * | 2013-12-30 | 2014-07-11 | Univ Pontificia Catolica Chile | Uso de necrostatina-1 para el tratamiento de la degeneracion axonal inducida por daños agudos y cronicos |
| WO2016094846A1 (en) * | 2014-12-11 | 2016-06-16 | President And Fellows Of Harvard College | Inhibitors of cellular necrosis and related methods |
| EP3265440A1 (en) | 2015-03-06 | 2018-01-10 | Concert Pharmaceuticals Inc. | Deuterated emricasan |
| RU2716136C2 (ru) | 2015-07-02 | 2020-03-06 | Ф. Хоффманн-Ля Рош Аг | Бициклические лактамы и способы их применения |
| US9815850B2 (en) | 2016-02-05 | 2017-11-14 | Denali Therapeutics Inc. | Compounds, compositions and methods |
| JP7349359B2 (ja) | 2016-10-17 | 2023-09-22 | エフ． ホフマン－ラ ロシュ アーゲー | 二環式ピリドンラクタム及びその使用方法。 |
| LT3552017T (lt) | 2016-12-09 | 2022-05-10 | Denali Therapeutics Inc. | Junginiai, naudotini kaip ripk1 inhibitoriai |
| US11072607B2 (en) | 2016-12-16 | 2021-07-27 | Genentech, Inc. | Inhibitors of RIP1 kinase and methods of use thereof |
| SG11202006304SA (en) * | 2017-12-31 | 2020-07-29 | Evergreen Biosciences | Compositions for cryopreservation and methods of use thereof |
| EP3781571B1 (en) | 2018-04-20 | 2024-01-17 | F. Hoffmann-La Roche AG | N-[4-oxo-2,3-dihydro-pyrido[3,2-b][1,4]oxazepin-3-yl]-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazole-2-carboxamide derivatives and related compounds as rip1 kinase inhibitors for treating e.g. irritable bowel syndrome (ibs) |
| RU2749634C1 (ru) * | 2020-11-30 | 2021-06-16 | Федеральное государственное бюджетное учреждение "Российский научный центр радиологии и хирургических технологий имени академика А.М. Гранова" Министерства здравоохранения Российской Федерации | Способ моделирования лечения больных с двигательными и висцеральными расстройствами на лабораторных животных. |
| EP4463229A1 (en) | 2022-01-12 | 2024-11-20 | Denali Therapeutics Inc. | Crystalline forms of (s)-5-benzyl-n-(5-methyl-4-oxo-2, 3,4,5- tetrahydropyrido [3,2-b] [l,4]oxazepin-3-yl)-4h-l,2,4-triazole-3-carboxamide |
| KR20250119466A (ko) * | 2024-01-31 | 2025-08-07 | (주)노보메디슨 | 캐스파제 저해제의 용도 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
| US5725493A (en) | 1994-12-12 | 1998-03-10 | Avery; Robert Logan | Intravitreal medicine delivery |
| US6299895B1 (en) | 1997-03-24 | 2001-10-09 | Neurotech S.A. | Device and method for treating ophthalmic diseases |
| DE69739105D1 (de) | 1996-11-20 | 2008-12-24 | Univ Yale | Survivin, ein protein das zelluläre apoptosis hemmt, und dessen modulation |
| JP2002534139A (ja) | 1999-01-05 | 2002-10-15 | マサチューセッツ・アイ・アンド・イア・インファーマリー | 網膜と脈絡膜への経強膜徐放性薬剤標的送達 |
| WO2001028493A2 (en) * | 1999-10-15 | 2001-04-26 | President And Fellows Of Harvard College | Small molecule inhibitors of necrosis |
| US6416777B1 (en) | 1999-10-21 | 2002-07-09 | Alcon Universal Ltd. | Ophthalmic drug delivery device |
| TR200201047T2 (tr) | 1999-10-21 | 2002-07-22 | Alcon, Inc. | İlaç verme vasıtası. |
| AU1920501A (en) | 1999-12-03 | 2001-06-12 | Alcon Universal Limited | The use of caspase 9 inhibitors to treat ocular neural pathology |
| US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
| US20030103945A1 (en) * | 2001-02-09 | 2003-06-05 | Chen Dong Feng | Methods and compositions for stimulating axon regeneration and preventing neuronal cell degeneration |
| WO2002089767A1 (en) | 2001-05-03 | 2002-11-14 | Massachusetts Eye And Ear Infirmary | Implantable drug delivery device and use thereof |
| WO2003061519A2 (en) | 2002-01-18 | 2003-07-31 | Massachusetts Eye And Ear Infirmary | Methods and compositions for preserving the viability of photoreceptor cells |
| US20050130877A1 (en) * | 2003-03-14 | 2005-06-16 | Children's Medical Center Corporation | Axon regeneration with PKC inhibitors |
| AU2004315596B2 (en) * | 2003-08-29 | 2011-11-24 | President And Fellows Of Harvard College | Inhibitors of cellular necrosis |
| US8912144B2 (en) * | 2003-12-16 | 2014-12-16 | Children's Medical Center Corporation | Method for treating stroke via administration of NEP1-40 and inosine |
| US20070298129A1 (en) | 2005-08-24 | 2007-12-27 | Neurotech Pharmaceuticals Co., Ltd. | Compounds and compositions for treating neuronal death or neurological dysfunction |
| US20070049565A1 (en) * | 2005-08-24 | 2007-03-01 | Neurotech Pharmaceuticals Co., Ltd. | Combination of cell necrosis inhibitor and lithium for treating neuronal death or neurological dysfunction |
| CA2633500A1 (en) * | 2005-12-20 | 2007-07-05 | President And Fellows Of Harvard College | Compounds, screens, and methods of treatment |
| CN102408470A (zh) | 2005-12-23 | 2012-04-11 | 洛桑大学 | 用作神经递质分泌抑制剂和肌肉松弛诱导物的合成肽 |
| JP5366812B2 (ja) * | 2006-10-10 | 2013-12-11 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | 化合物、スクリーニング、および治療方法 |
| US20090022570A1 (en) * | 2007-07-16 | 2009-01-22 | Joe David Craig | System, method and apparatus for feeding biomass into a pressurized vessel |
| CA2696349A1 (en) * | 2007-08-15 | 2009-02-19 | President And Fellows Of Harvard College | Heterocyclic inhibitors of necroptosis |
| JP2012500283A (ja) * | 2008-08-19 | 2012-01-05 | ノップ ニューロサイエンシーズ、インク． | （ｒ）−プラミペキソールを使用した組成物並びにその方法 |
| WO2010075290A1 (en) | 2008-12-22 | 2010-07-01 | President And Fellows Of Harvard College | Unsaturated heterocyclic inhibitors of necroptosis |
| US7622106B1 (en) | 2009-03-06 | 2009-11-24 | Board Of Regents, The University Of Texas System | Necrosis assay |
| JP5723294B2 (ja) | 2009-12-09 | 2015-05-27 | 北海道公立大学法人 札幌医科大学 | スーパーオキシド製造方法、スーパーオキシド消去能評価方法、スーパーオキシド製造装置およびスーパーオキシド消去能評価装置 |
| US20130137642A1 (en) | 2010-04-23 | 2013-05-30 | Demetrios Vavvas | Methods and compositions for preserving photoreceptor and retinal pigment epithelial cells |
| US20140024598A1 (en) | 2010-11-01 | 2014-01-23 | Demetrios Vavvas | Methods and compositions for preserving retinal ganglion cells |
| EP2773341A2 (en) | 2011-10-21 | 2014-09-10 | Massachusetts Eye & Ear Infirmary | Compositions comprising necrosis inhibitors, such as necrostatins, alone or in combination, for promoting axon regeneration and nerve function, thereby treating cns disorders |
-
2012
- 2012-10-22 EP EP12780381.5A patent/EP2773341A2/en not_active Withdrawn
- 2012-10-22 JP JP2014537360A patent/JP6254090B2/ja active Active
- 2012-10-22 CA CA2888805A patent/CA2888805C/en not_active Expired - Fee Related
- 2012-10-22 HK HK15102094.4A patent/HK1203044A1/xx unknown
- 2012-10-22 US US14/352,960 patent/US20140357570A1/en not_active Abandoned
- 2012-10-22 WO PCT/US2012/061324 patent/WO2013059791A2/en not_active Ceased
-
2015
- 2015-11-02 US US14/930,501 patent/US10022419B2/en active Active
-
2017
- 2017-11-29 JP JP2017228601A patent/JP6560325B2/ja not_active Expired - Fee Related
-
2018
- 2018-06-22 US US16/015,947 patent/US10799552B2/en active Active
-
2019
- 2019-07-18 JP JP2019132740A patent/JP6861764B2/ja not_active Expired - Fee Related
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