TWI629274B - 用於治療脊椎肌肉萎縮症之化合物 - Google Patents
用於治療脊椎肌肉萎縮症之化合物 Download PDFInfo
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- TWI629274B TWI629274B TW106106161A TW106106161A TWI629274B TW I629274 B TWI629274 B TW I629274B TW 106106161 A TW106106161 A TW 106106161A TW 106106161 A TW106106161 A TW 106106161A TW I629274 B TWI629274 B TW I629274B
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Classifications
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- C07D471/02—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 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- 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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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
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Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10327940B2 (en) | 2008-11-09 | 2019-06-25 | 3D Systems, Inc. | Spiral brace |
| CN104244944B (zh) | 2011-12-30 | 2018-06-08 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩症的化合物 |
| JP6193888B2 (ja) | 2012-01-26 | 2017-09-06 | ピーティーシー セラピューティクス, インコーポレイテッド | 脊髄性筋萎縮症を治療するための化合物 |
| PL2812004T3 (pl) | 2012-02-10 | 2019-01-31 | Ptc Therapeutics, Inc. | Związki do leczenia rdzeniowego zaniku mięśni |
| CN104302181B (zh) | 2012-03-01 | 2017-09-15 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩的化合物 |
| EA028382B1 (ru) | 2012-03-23 | 2017-11-30 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения спинальной мышечной атрофии |
| CA2894992A1 (en) * | 2012-12-24 | 2014-07-03 | Ramot At Tel-Aviv University Ltd. | Agents for treating genetic diseases resulting from nonsense mutations, and methods for identifying the same |
| CN105392790B (zh) * | 2013-08-19 | 2019-04-19 | 豪夫迈·罗氏有限公司 | 4H-吡啶并[1,2-a]嘧啶-4-酮化合物制备用于预防或治疗癌症的药物的用途 |
| EP3082820B1 (en) * | 2013-12-19 | 2022-07-20 | PTC Therapeutics, Inc. | Methods for modulating the amount of rna transcripts |
| US10882868B2 (en) | 2014-05-15 | 2021-01-05 | Hoffmann-La Roche Inc. | Compounds for treating spinal muscular atrophy |
| ES2949660T3 (es) * | 2014-05-15 | 2023-10-02 | Hoffmann La Roche | Procedimiento para la preparación de compuestos útiles para tratar la atrofia muscular espinal |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| BR112017004056A2 (pt) | 2014-09-12 | 2017-12-05 | Biogen Ma Inc | composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo |
| AU2015327836B2 (en) | 2014-10-03 | 2021-07-01 | Cold Spring Harbor Laboratory | Targeted augmentation of nuclear gene output |
| AU2015341186B2 (en) * | 2014-11-01 | 2019-11-14 | Fochon Biosciences, Ltd. | Certain protein kinase inhibitors |
| EP3242763A4 (en) * | 2015-01-05 | 2018-08-29 | Sikorsky Aircraft Corporation | Integrated vibration damper for additively manufactured structure and method |
| JP6749343B2 (ja) | 2015-05-20 | 2020-09-02 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 脊髄性筋萎縮症を処置するための化合物 |
| US10668171B2 (en) * | 2015-05-30 | 2020-06-02 | Ptc Therapeutics, Inc. | Methods for modulating RNA splicing |
| EP3359685A1 (en) | 2015-10-09 | 2018-08-15 | University Of Southampton | Modulation of gene expression and screening for deregulated protein expression |
| EP3374362A1 (en) * | 2015-11-12 | 2018-09-19 | H. Hoffnabb-La Roche Ag | Compounds for treating amyotrophic lateral sclerosis |
| KR102162062B1 (ko) * | 2015-11-12 | 2020-10-07 | 에프. 호프만-라 로슈 아게 | 척수성 근위축증의 치료용 조성물 |
| DK3386591T3 (da) | 2015-12-09 | 2020-09-28 | Cadent Therapeutics Inc | Heteroaromatic nmda receptor modulators and uses thereof |
| CN113750101A (zh) | 2015-12-10 | 2021-12-07 | Ptc医疗公司 | 用于治疗亨廷顿病的方法 |
| EP3386978B1 (en) | 2015-12-10 | 2021-01-27 | H. Hoffnabb-La Roche Ag | Bridged piperidine derivatives |
| ES2882500T3 (es) | 2015-12-14 | 2021-12-02 | Cold Spring Harbor Laboratory | Oligómeros antisentido para el tratamiento del síndrome de Dravet |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| WO2017186668A1 (en) | 2016-04-28 | 2017-11-02 | F. Hoffmann-La Roche Ag | A process for the preparation of 2-pyrazolo[1,5-a]pyrazin-2-ylpyrido[1,2-a]pyrimidin-4-one |
| EP3471779A4 (en) | 2016-06-16 | 2020-07-08 | Ionis Pharmaceuticals, Inc. | COMBINATIONS FOR MODULATING SMN EXPRESSION |
| EA201991309A1 (ru) * | 2016-11-28 | 2019-11-29 | Способы модуляции сплайсинга рнк | |
| US11274107B2 (en) | 2016-12-22 | 2022-03-15 | Cadent Therapeutics, Inc. | NMDA receptor modulators and uses thereof |
| US11407753B2 (en) | 2017-06-05 | 2022-08-09 | Ptc Therapeutics, Inc. | Compounds for treating Huntington's disease |
| CN111372611A (zh) | 2017-06-14 | 2020-07-03 | Ptc医疗公司 | 修饰rna剪接的方法 |
| EP3645121B8 (en) | 2017-06-28 | 2025-06-18 | PTC Therapeutics, Inc. | Methods for treating huntington's disease |
| CA3067591A1 (en) * | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | Methods for treating huntington's disease |
| SG10202002990XA (en) | 2017-08-04 | 2020-05-28 | Skyhawk Therapeutics Inc | Methods and compositions for modulating splicing |
| RS65031B1 (sr) | 2017-08-25 | 2024-02-29 | Stoke Therapeutics Inc | Antisens oligomeri za lečenje stanja i bolesti |
| CN111132981B (zh) * | 2017-09-22 | 2023-10-31 | 豪夫迈·罗氏有限公司 | 制备吡啶并[1,2-a]嘧啶-4-酮衍生物的方法 |
| PL3700570T3 (pl) | 2017-10-23 | 2025-05-05 | Stoke Therapeutics, Inc. | Oligomery antysensowne w leczeniu schorzeń oraz chorób wynikających z degradacji rna zgodnie z nmd |
| KR20210005559A (ko) | 2018-03-27 | 2021-01-14 | 피티씨 테라퓨틱스, 인크. | 헌팅턴병 치료 화합물 |
| JP2021523227A (ja) | 2018-05-04 | 2021-09-02 | ストーク セラピューティクス,インク. | コレステリルエステル蓄積症の処置のための方法及び組成物 |
| LT3814357T (lt) | 2018-06-27 | 2024-06-25 | Ptc Therapeutics, Inc. | Heterocikliniai ir heteroarilų junginiai, skirti hantingtono ligos gydymui |
| CN112469707B (zh) * | 2018-06-27 | 2024-06-21 | 利伯纳生物科学株式会社 | 脊髓性肌萎缩症的预防剂或治疗剂 |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| US11685746B2 (en) | 2018-06-27 | 2023-06-27 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating Huntington's disease |
| HUE062566T2 (hu) | 2018-08-03 | 2023-11-28 | Novartis Ag | Heteroaromás NMDA receptor modulátorok és alkalmazásaik |
| CN112805009A (zh) * | 2018-08-07 | 2021-05-14 | 费城儿童医院 | 基因表达的选择性剪接调控及治疗方法 |
| KR20210135241A (ko) | 2019-02-05 | 2021-11-12 | 스카이호크 테라퓨틱스, 인코포레이티드 | 스플라이싱을 조절하는 방법 및 조성물 |
| KR20210135507A (ko) | 2019-02-06 | 2021-11-15 | 스카이호크 테라퓨틱스, 인코포레이티드 | 스플라이싱을 조절하는 방법 및 조성물 |
| US11129829B2 (en) | 2019-06-17 | 2021-09-28 | Skyhawk Therapeutics, Inc. | Methods for modulating splicing |
| CN110540535B (zh) * | 2019-10-23 | 2020-07-31 | 上海再启生物技术有限公司 | 适合放大制备4-(6-氨基吡啶-3-基)取代哌啶的工艺方法 |
| CN111116576A (zh) * | 2019-12-01 | 2020-05-08 | 北京师范大学 | 一种喹嗪酮类化合物及其制备方法 |
| MX2022006700A (es) | 2019-12-02 | 2022-09-02 | Storm Therapeutics Ltd | Compuestos poliheterociclicos como inhibidores de mettl3. |
| EP4097092A1 (en) | 2020-01-28 | 2022-12-07 | Protego Biopharma, Inc. | Compounds, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
| CN115605596A (zh) * | 2020-02-12 | 2023-01-13 | 费城儿童医院(Us) | 用于基因表达的诱导型可变剪接调节的组合物和方法 |
| US20230148184A1 (en) | 2020-02-28 | 2023-05-11 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| CA3169697A1 (en) | 2020-02-28 | 2021-09-02 | Dominic Reynolds | Thiophenyl derivatives useful for modulating nucleic acid splicing |
| WO2021174176A1 (en) | 2020-02-28 | 2021-09-02 | Remix Therapeutics Inc. | Pyridazine dervatives for modulating nucleic acid splicing |
| AR121446A1 (es) | 2020-02-28 | 2022-06-08 | Ionis Pharmaceuticals Inc | Compuestos y métodos para modular smn2 |
| EP4110464A1 (en) | 2020-02-28 | 2023-01-04 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| CA3175193A1 (en) | 2020-04-08 | 2021-10-14 | Dominic Reynolds | Compounds and methods for modulating splicing |
| EP4132646A1 (en) | 2020-04-08 | 2023-02-15 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| AU2021270720A1 (en) | 2020-05-11 | 2022-12-08 | Stoke Therapeutics, Inc. | OPA1 antisense oligomers for treatment of conditions and diseases |
| JP2023532331A (ja) | 2020-07-02 | 2023-07-27 | リミックス セラピューティクス インコーポレイテッド | 核酸をスプライシングするため及び増殖性疾患を処置するための修飾因子としての5-[5-(ピペリジン-4-イル)チエノ[3,2-c]ピラゾール-2-イル]インダゾール誘導体及び関連する化合物並びにスプライシングを調節するための化合物及び方法 |
| TW202216710A (zh) | 2020-07-02 | 2022-05-01 | 美商雷密克斯醫療公司 | 調節剪接之化合物及方法 |
| WO2022070071A1 (en) * | 2020-09-30 | 2022-04-07 | Janssen Biotech, Inc. | Dihydroorotate dehydrogenase inhibitors |
| CR20230437A (es) | 2021-03-17 | 2023-10-16 | Hoffmann La Roche | Nuevos derivados de tiazolopirimidinona |
| TW202321206A (zh) | 2021-07-28 | 2023-06-01 | 美商普羅泰戈生物製藥股份有限公司 | 轉甲狀腺素蛋白穩定化合物 |
| KR20240096913A (ko) | 2021-08-30 | 2024-06-26 | 레믹스 테라퓨틱스 인크. | 스플라이싱 조절을 위한 화합물 및 방법 |
| EP4396177A1 (en) | 2021-08-30 | 2024-07-10 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| WO2023034811A1 (en) | 2021-08-30 | 2023-03-09 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| EP4395890A1 (en) | 2021-08-30 | 2024-07-10 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| US20240400584A1 (en) | 2021-08-30 | 2024-12-05 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| EP4416156A1 (en) | 2021-10-13 | 2024-08-21 | Remix Therapeutics Inc. | Compounds and methods for modulating nucleic acid splicing |
| AU2022365100A1 (en) * | 2021-10-13 | 2024-05-02 | Remix Therapeutics Inc. | Compounds and methods for modulating nucleic acid splicing |
| US20250109140A1 (en) | 2022-01-05 | 2025-04-03 | Remix Theraputics Inc. | 5-[5-(piperidin-4-yl)thieno[3,2-c]pyrazol-2-yl]indazole derivatives and related compounds as modulators for splicing nucleic acids and for the treatment of proliferative diseases |
| TW202337442A (zh) | 2022-01-05 | 2023-10-01 | 美商雷密克斯醫療公司 | 用於調節剪切之化合物及方法 |
| US20250326748A1 (en) | 2022-01-05 | 2025-10-23 | Remix Therapeutics Inc. | Compounds and methods for modulating splicing |
| WO2023240236A1 (en) | 2022-06-10 | 2023-12-14 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of spinal muscular atrophy related disorders |
| AU2024286618A1 (en) * | 2023-06-09 | 2025-10-30 | F. Hoffmann-La Roche Ag | Inducible gene expression system |
| CN117263936B (zh) * | 2023-11-21 | 2024-02-23 | 中国中医科学院医学实验中心 | 一种咪唑并[1, 2-a]吡啶衍生物及其制备方法和在中枢神经系统渗透性HDAC6抑制药物中的应用 |
| WO2025233837A1 (en) | 2024-05-07 | 2025-11-13 | Takeda Pharmaceutical Company Limited | 4h-pyrimido[1,2-a]pyrimidin-4-one derivatives for use as nlrp3 inflammasome inhibitors for the treatment of neurodegenerative disorder |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4122274A (en) * | 1977-05-25 | 1978-10-24 | Bristol-Myers Company | 3-Tetrazolo-5,6,7,8-substituted-pyrido[1,2-a]pyrimidin-4-ones |
| EP1227084A1 (en) * | 1999-10-28 | 2002-07-31 | Microcide Pharmaceuticals, Inc. | Drug discharge pump inhibitors |
| US6977255B2 (en) * | 2000-01-24 | 2005-12-20 | Kinacia Pty. Ltd. | Therapeutic morpholino-substituted compounds |
| WO2011050245A1 (en) * | 2009-10-23 | 2011-04-28 | Yangbo Feng | Bicyclic heteroaryls as kinase inhibitors |
| TWI585085B (zh) * | 2012-02-10 | 2017-06-01 | Ptc治療公司 | 用於治療脊椎肌肉萎縮症之化合物 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3558618A (en) * | 1968-04-01 | 1971-01-26 | Dow Chemical Co | Novel 4h-pyrazino(1,2-a)pyrimidine-4-ones |
| US4342870A (en) | 1980-03-28 | 1982-08-03 | Janssen Pharmaceutica N.V. | Novel 3-(1-piperidinylalkyl)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives |
| JPS56150091A (en) * | 1980-03-28 | 1981-11-20 | Janssen Pharmaceutica Nv | 3-(1-piperidinylalkyl)-4h-pyrido(1,2-a)pyrimidine- 4-one derivative and its manufacture |
| US5089633A (en) | 1987-04-28 | 1992-02-18 | Georgia Tech Research Corporation | Substituted isocoumarins |
| US5599816A (en) | 1990-05-02 | 1997-02-04 | Abbott Laboratories | Quinolizinone type compounds |
| WO1993023398A1 (en) * | 1992-05-13 | 1993-11-25 | E.I. Du Pont De Nemours And Company | Substituted pyrido[1,2-a]pyrimidinone derivatives as fungicides |
| IL122296A0 (en) | 1995-06-06 | 1998-04-05 | Abbott Lab | Quinolizinone type compounds |
| US5869500A (en) | 1996-12-13 | 1999-02-09 | Hoffmann-La Roche Inc. | Pyridone compounds useful in treating Alzheimer's disease |
| WO2000017197A1 (en) * | 1998-09-21 | 2000-03-30 | Biochem Pharma Inc. | Quinolizinones as integrin inhibitors |
| CA2665516A1 (en) | 2001-04-26 | 2002-11-07 | Daiichi Pharmaceutical Co., Ltd. | Drug efflux pump inhibitor |
| EP1474147B1 (en) | 2001-12-07 | 2010-05-05 | Vertex Pharmaceuticals Incorporated | Pyrimidine-based compounds useful as gsk-3 inhibitors |
| GB0205281D0 (en) | 2002-03-06 | 2002-04-17 | Novartis Ag | Organic compounds |
| ATE548354T1 (de) | 2002-07-24 | 2012-03-15 | Ptc Therapeutics Inc | Ureido-substituierte benzoesäureverbindungen und ihre verwendung für die nonsense-suppression und behandlung von erkrankungen |
| AU2004249730A1 (en) * | 2003-06-20 | 2004-12-29 | Novartis Vaccines And Diagnostics, Inc. | Pyridino(1,2-A)pyrimidin-4-one compounds as anticancer agents |
| WO2005105801A1 (en) | 2004-05-04 | 2005-11-10 | Warner-Lambert Company Llc | Pyrrolyl substituted pyrido[2,3-d]pyrimidin-7-ones and derivatives thereof as therapeutic agents |
| EP1846397A1 (en) | 2005-01-21 | 2007-10-24 | Janssen Pharmaceutica N.V. | Novel heterocyclic benzoy[c]chromene derivatives useful as modulators of the estrogen receptors |
| AR059339A1 (es) | 2006-02-09 | 2008-03-26 | Chugai Pharmaceutical Co Ltd | Derivados de la cumarina para trastornos proliferativos de celulas, composicion farmaceutica y agente terapeutico que los contiene |
| US8110681B2 (en) * | 2006-03-17 | 2012-02-07 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Compounds for the treatment of spinal muscular atrophy and other uses |
| WO2008013997A2 (en) | 2006-07-27 | 2008-01-31 | The Trustees Of Columbia University In The City Of New York | Fluorescent substrates for monoamine transporters as optical false neurotransmitters |
| US8633019B2 (en) | 2008-05-27 | 2014-01-21 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| EP2138493A1 (en) * | 2008-06-26 | 2009-12-30 | Sanofi-Aventis | Substituted pyrimidone derivatives |
| US8986935B2 (en) | 2008-08-13 | 2015-03-24 | Ptc Therapeutics, Inc. | Methods for treating spinal muscular atrophy |
| US8754220B2 (en) * | 2009-11-20 | 2014-06-17 | Merck Sharp & Dohme Corp. | Quinolizidinone carboxamide M1 receptor positive allosteric modulators |
| CA2786329A1 (en) * | 2010-01-13 | 2011-07-21 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Anti - infective pyrido (1,2-a) pyrimidines |
| CN104244944B (zh) | 2011-12-30 | 2018-06-08 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩症的化合物 |
| JP6193888B2 (ja) | 2012-01-26 | 2017-09-06 | ピーティーシー セラピューティクス, インコーポレイテッド | 脊髄性筋萎縮症を治療するための化合物 |
| CN104302181B (zh) | 2012-03-01 | 2017-09-15 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩的化合物 |
| EA028382B1 (ru) | 2012-03-23 | 2017-11-30 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения спинальной мышечной атрофии |
| ES2949660T3 (es) | 2014-05-15 | 2023-10-02 | Hoffmann La Roche | Procedimiento para la preparación de compuestos útiles para tratar la atrofia muscular espinal |
| JP6749343B2 (ja) | 2015-05-20 | 2020-09-02 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 脊髄性筋萎縮症を処置するための化合物 |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4122274A (en) * | 1977-05-25 | 1978-10-24 | Bristol-Myers Company | 3-Tetrazolo-5,6,7,8-substituted-pyrido[1,2-a]pyrimidin-4-ones |
| EP1227084A1 (en) * | 1999-10-28 | 2002-07-31 | Microcide Pharmaceuticals, Inc. | Drug discharge pump inhibitors |
| US6977255B2 (en) * | 2000-01-24 | 2005-12-20 | Kinacia Pty. Ltd. | Therapeutic morpholino-substituted compounds |
| WO2011050245A1 (en) * | 2009-10-23 | 2011-04-28 | Yangbo Feng | Bicyclic heteroaryls as kinase inhibitors |
| TWI585085B (zh) * | 2012-02-10 | 2017-06-01 | Ptc治療公司 | 用於治療脊椎肌肉萎縮症之化合物 |
Non-Patent Citations (3)
| Title |
|---|
| Knight Zachary A. et al.;"Isoform-specific phosphoinositide 3-Kinase inhibitors from an arylmorpholine scaffold";Bioorganic & Medicinal Chemistry,2004,vol.12,pages 4749-4759. |
| Peng Lijie et al.;"Identification of Pyrido[1,2-α]pyrimidine-4-ones as New Molecules Improving the Transcriptional Functions of Estrogen-Related Receptor α";Journal of Medicinal Chemistry,2011,vol.54,pages 7729-7733. |
| Peng Lijie et al.;"Identification of Pyrido[1,2-α]pyrimidine-4-ones as New Molecules Improving the Transcriptional Functions of Estrogen-Related Receptor α";Journal of Medicinal Chemistry,2011,vol.54,pages 7729-7733. Knight Zachary A. et al.;"Isoform-specific phosphoinositide 3-Kinase inhibitors from an arylmorpholine scaffold";Bioorganic & Medicinal Chemistry,2004,vol.12,pages 4749-4759. * |
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