CA2952959C - Use of nucleosides and nucleotides to treat filoviridae viral infection - Google Patents
Use of nucleosides and nucleotides to treat filoviridae viral infection Download PDFInfo
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- CA2952959C CA2952959C CA2952959A CA2952959A CA2952959C CA 2952959 C CA2952959 C CA 2952959C CA 2952959 A CA2952959 A CA 2952959A CA 2952959 A CA2952959 A CA 2952959A CA 2952959 C CA2952959 C CA 2952959C
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- alkyl
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Classifications
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- A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
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Landscapes
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- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
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- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Oncology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2860234A1 (en) | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| AU2012358803C1 (en) | 2011-12-22 | 2019-12-19 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| HK1206362A1 (zh) | 2012-03-21 | 2016-01-08 | Alios Biopharma, Inc. | 硫代氨基磷酸酯核苷酸前藥的固體形式 |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| AU2013361193B2 (en) | 2012-12-21 | 2018-05-24 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| JP6284547B2 (ja) | 2012-12-21 | 2018-02-28 | アリオス バイオファーマ インク. | 置換ヌクレオシド、置換ヌクレオチドおよびそれらの類似体 |
| CA2908313A1 (en) | 2013-04-05 | 2014-10-09 | Alios Biopharma, Inc. | Hepatitis c viral infection treatment using a combination of compounds |
| AU2014302715B2 (en) | 2013-06-26 | 2018-12-06 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9815864B2 (en) | 2013-06-26 | 2017-11-14 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| EP3055319A4 (en) | 2013-10-11 | 2018-01-10 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| CN106573011A (zh) | 2014-06-24 | 2017-04-19 | 艾丽奥斯生物制药有限公司 | 取代的核苷、核苷酸和其类似物 |
| US9603863B2 (en) | 2014-06-24 | 2017-03-28 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| EP3197457B1 (en) | 2014-09-26 | 2022-11-09 | Riboscience LLC | 4'-vinyl substituted nucleoside derivatives as inhibitors of respiratory syncytial virus rna replication |
| US20170246209A1 (en) * | 2014-10-06 | 2017-08-31 | Nantkwest, Inc. | Treating viral hemorrhagic fever with nk-92 cells |
| WO2016069489A1 (en) | 2014-10-28 | 2016-05-06 | Alios Biopharma, Inc. | Methods of preparing substituted nucleoside analogs |
| MA41213A (fr) | 2014-12-19 | 2017-10-24 | Alios Biopharma Inc | Nucléosides substitués, nucléotides et analogues de ceux-ci |
| MA41441A (fr) | 2014-12-19 | 2017-12-12 | Alios Biopharma Inc | Nucléosides substitués, nucléotides et analogues de ceux-ci |
| SG11201705069YA (en) | 2014-12-26 | 2017-07-28 | Univ Emory | N4-hydroxycytidine and derivatives and anti-viral uses related thereto |
| MY190867A (en) | 2015-03-06 | 2022-05-13 | Atea Pharmaceuticals Inc | ? -d-2'-deoxy-2'-?-fluoro-2'- ? -c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment |
| MX383931B (es) | 2015-03-11 | 2025-03-14 | Janssen Biopharma Inc | Compuestos de aza-piridona y usos de estos. |
| US11192914B2 (en) * | 2016-04-28 | 2021-12-07 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| US10202412B2 (en) | 2016-07-08 | 2019-02-12 | Atea Pharmaceuticals, Inc. | β-D-2′-deoxy-2′-substituted-4′-substituted-2-substituted-N6-substituted-6-aminopurinenucleotides for the treatment of paramyxovirus and orthomyxovirus infections |
| PL3512863T3 (pl) | 2016-09-07 | 2022-04-04 | Atea Pharmaceuticals, Inc. | 2'-Podstawione-N6-podstawione nukleotydy purynowe do leczenia zakażeń wirusem RNA |
| IL295609B2 (en) | 2017-02-01 | 2023-11-01 | Atea Pharmaceuticals Inc | Nucleotide hemisulfate salt for the treatment of hepatitis C virus |
| JP2020518578A (ja) | 2017-05-01 | 2020-06-25 | ギリアード サイエンシーズ, インコーポレイテッド | (S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエートの結晶形態 |
| ES3000461T3 (en) | 2017-07-11 | 2025-02-28 | Gilead Sciences Inc | Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections |
| KR102696517B1 (ko) | 2017-09-18 | 2024-08-21 | 얀센 바이오파마, 인크. | 치환된 뉴클레오시드, 뉴클레오티드 및 이들의 유사체 |
| PL3706762T3 (pl) | 2017-12-07 | 2025-02-10 | Emory University | N4-hydroksycytydyna i pochodne oraz związane z nimi zastosowania przeciwwirusowe |
| KR20200140274A (ko) * | 2018-03-07 | 2020-12-15 | 에모리 유니버시티 | 4'-할로겐 함유 뉴클레오티드 및 뉴클레오시드 치료 조성물 및 이와 관련된 용도 |
| CN112351799A (zh) | 2018-04-10 | 2021-02-09 | 阿堤亚制药公司 | 具有硬化的hcv感染患者的治疗 |
| PH12021500034A1 (en) | 2019-03-06 | 2022-06-06 | Glaxosmithkline Ip No 2 Ltd | Compounds useful in hiv therapy |
| SG11202110742TA (en) * | 2019-04-02 | 2021-10-28 | Aligos Therapeutics Inc | Compounds targeting prmt5 |
| JP2023512656A (ja) | 2020-01-27 | 2023-03-28 | ギリアード サイエンシーズ, インコーポレイテッド | SARS CoV-2感染を治療するための方法 |
| TWI794742B (zh) | 2020-02-18 | 2023-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| AR121356A1 (es) * | 2020-02-18 | 2022-05-11 | Gilead Sciences Inc | Compuestos antivirales |
| TWI775313B (zh) | 2020-02-18 | 2022-08-21 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| TWI890963B (zh) | 2020-03-12 | 2025-07-21 | 美商基利科學股份有限公司 | 1'-氰基核苷之製備方法 |
| AR121620A1 (es) | 2020-03-20 | 2022-06-22 | Gilead Sciences Inc | Profármacos de nucleósidos 4-c-sustituidos-2-halo-2-deoxiadenosina y métodos de preparación y uso de los mismos |
| AU2021251689B2 (en) | 2020-04-06 | 2024-06-13 | Gilead Sciences, Inc. | Inhalation formulations of 1'-cyano substituted carbanucleoside analogs |
| KR20230002592A (ko) * | 2020-04-14 | 2023-01-05 | 얀센 파마슈티칼즈, 인코포레이티드 | E형 간염의 치료를 위한 바이사이클릭 및 모노사이클릭 뉴클레오시드 유사체 |
| TW202532084A (zh) | 2020-05-29 | 2025-08-16 | 美商基利科學股份有限公司 | 瑞德西韋之治療方法 |
| IL299202A (en) | 2020-06-24 | 2023-02-01 | Gilead Sciences Inc | 1'-cyano nucleoside analogs and uses thereof |
| US11773122B2 (en) | 2020-08-24 | 2023-10-03 | Gilead Sciences. Inc. | Phospholipid compounds and uses thereof |
| PE20231983A1 (es) | 2020-08-27 | 2023-12-12 | Gilead Sciences Inc | Compuestos y metodos para el tratamiento de infecciones virales |
| TWI811812B (zh) | 2020-10-16 | 2023-08-11 | 美商基利科學股份有限公司 | 磷脂化合物及其用途 |
| ES3028915T3 (en) | 2021-04-16 | 2025-06-20 | Gilead Sciences Inc | Methods of preparing carbanucleosides using amides |
| BR112023026356A2 (pt) | 2021-06-17 | 2024-03-05 | Atea Pharmaceuticals Inc | Método para tratar vírus da hepatite c ou uma condição resultante de uma infecção por hepatite c, combinação, uso da combinação, composição farmacêutica, e, kit para o tratamento de vírus da hepatite c |
| CN113735929A (zh) * | 2021-07-21 | 2021-12-03 | 海化生命(厦门)科技有限公司 | 一种抗冠状病毒的化合物及其制备方法与应用 |
| EP4387977A1 (en) | 2021-08-18 | 2024-06-26 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
| US11541071B1 (en) | 2021-12-16 | 2023-01-03 | Ascletis BioScience Co., Ltd | Nucleoside derivatives and methods of use thereof |
| CN116554249B (zh) * | 2022-01-28 | 2025-03-18 | 北京恩泰伟医药科技有限公司 | 抗病毒化合物及其用途 |
| CA3244278A1 (en) | 2022-03-02 | 2023-09-07 | Gilead Sciences Inc | COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS |
| IL315480A (en) | 2022-03-15 | 2024-11-01 | Rome Therapeutics Inc | Compounds and methods for treating disease |
| CN115322170B (zh) * | 2022-08-29 | 2023-06-02 | 苏州华一新能源科技股份有限公司 | 一种硫酸乙烯酯的制备方法 |
| CN116589510B (zh) * | 2023-04-20 | 2025-08-26 | 安徽大学 | 一种氟代苄基核糖中间体的制备方法与应用 |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| HUP0400726A3 (en) | 2001-01-22 | 2007-05-29 | Merck & Co Inc | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| WO2002069903A2 (en) | 2001-03-06 | 2002-09-12 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| US20040138170A1 (en) | 2002-03-06 | 2004-07-15 | Montgomery John A. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| CA2537450C (en) * | 2003-09-05 | 2012-04-17 | Anadys Pharmaceuticals, Inc. | Administration of tlr7 ligands and prodrugs thereof for treatment of infection by hepatitis c virus |
| WO2006033709A2 (en) | 2004-07-29 | 2006-03-30 | Metabasis Therapeutics, Inc. | Novel nucleoside derivatives |
| US20090318380A1 (en) * | 2007-11-20 | 2009-12-24 | Pharmasset, Inc. | 2',4'-substituted nucleosides as antiviral agents |
| US20090176732A1 (en) | 2007-12-21 | 2009-07-09 | Alios Biopharma Inc. | Protected nucleotide analogs |
| US8475804B2 (en) | 2009-02-20 | 2013-07-02 | U.S. Army Medical Research And Material Command | Compositions and methods for treatment of filovirus-mediated diseases |
| US20100240604A1 (en) | 2009-03-20 | 2010-09-23 | Alios Biopharma, Inc. | Protected nucleotide analogs |
| EP2623104A1 (en) * | 2009-03-20 | 2013-08-07 | Alios Biopharma, Inc. | Substituted nucleoside and nucleotide analogs |
| WO2012040126A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| CA2810928A1 (en) * | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| WO2012040124A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
| AU2011349278C1 (en) | 2010-12-22 | 2017-01-19 | Alios Biopharma, Inc. | Cyclic nucleotide analogs |
| US9108999B2 (en) | 2011-12-20 | 2015-08-18 | Riboscience Llc | 2′, 4′-difluoro-2′-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication |
| AU2012358803C1 (en) | 2011-12-22 | 2019-12-19 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| CA2860234A1 (en) | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| HK1206362A1 (zh) | 2012-03-21 | 2016-01-08 | Alios Biopharma, Inc. | 硫代氨基磷酸酯核苷酸前藥的固體形式 |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| HK1203513A1 (en) | 2012-03-21 | 2015-10-30 | 艾丽奥斯生物制药有限公司 | Methods of preparing substituted nucleotide analogs |
| WO2013142159A1 (en) | 2012-03-21 | 2013-09-26 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| SG10201804571TA (en) * | 2012-03-21 | 2018-07-30 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| US9012427B2 (en) | 2012-03-22 | 2015-04-21 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| AU2013361193B2 (en) | 2012-12-21 | 2018-05-24 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| JP6284547B2 (ja) | 2012-12-21 | 2018-02-28 | アリオス バイオファーマ インク. | 置換ヌクレオシド、置換ヌクレオチドおよびそれらの類似体 |
| TW201526899A (zh) | 2013-02-28 | 2015-07-16 | Alios Biopharma Inc | 醫藥組成物 |
| WO2014164533A1 (en) | 2013-03-11 | 2014-10-09 | Vertex Pharmaceuticals Incorporated | Methods of stereoselective synthesis of substituted nucleoside analogs |
| CA2908313A1 (en) | 2013-04-05 | 2014-10-09 | Alios Biopharma, Inc. | Hepatitis c viral infection treatment using a combination of compounds |
| AU2014302715B2 (en) | 2013-06-26 | 2018-12-06 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9815864B2 (en) | 2013-06-26 | 2017-11-14 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| PL3043803T3 (pl) * | 2013-09-11 | 2022-11-07 | Emory University | Kompozycje nukleotydowe i nukleozydowe oraz ich zastosowanie |
| EP3055319A4 (en) | 2013-10-11 | 2018-01-10 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9603863B2 (en) | 2014-06-24 | 2017-03-28 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| BR112016029994A2 (pt) | 2014-06-24 | 2017-08-22 | Alios Biopharma Inc | métodos de preparação de análogos de nucleotídeo substituídos |
| CN106573011A (zh) | 2014-06-24 | 2017-04-19 | 艾丽奥斯生物制药有限公司 | 取代的核苷、核苷酸和其类似物 |
| US20160022724A1 (en) | 2014-07-22 | 2016-01-28 | Alios Biopharma, Inc. | Methods for treating paramyxoviruses |
| WO2016022464A1 (en) | 2014-08-05 | 2016-02-11 | Alios Biopharma, Inc. | Combination therapy for treating a paramyxovirus |
| WO2016069489A1 (en) | 2014-10-28 | 2016-05-06 | Alios Biopharma, Inc. | Methods of preparing substituted nucleoside analogs |
| MA41441A (fr) | 2014-12-19 | 2017-12-12 | Alios Biopharma Inc | Nucléosides substitués, nucléotides et analogues de ceux-ci |
| MA41213A (fr) | 2014-12-19 | 2017-10-24 | Alios Biopharma Inc | Nucléosides substitués, nucléotides et analogues de ceux-ci |
| EP3497111A2 (en) | 2016-08-12 | 2019-06-19 | Janssen BioPharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US20180117042A1 (en) | 2016-10-27 | 2018-05-03 | Alios Biopharma, Inc. | Methods for treating respiratory syncytial virus infection |
| KR102696517B1 (ko) | 2017-09-18 | 2024-08-21 | 얀센 바이오파마, 인크. | 치환된 뉴클레오시드, 뉴클레오티드 및 이들의 유사체 |
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| US10780105B2 (en) | 2020-09-22 |
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