JP2017538722A - 置換ヌクレオシド、ヌクレオチド、及びそのアナログ - Google Patents
置換ヌクレオシド、ヌクレオチド、及びそのアナログ Download PDFInfo
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- JP2017538722A JP2017538722A JP2017532656A JP2017532656A JP2017538722A JP 2017538722 A JP2017538722 A JP 2017538722A JP 2017532656 A JP2017532656 A JP 2017532656A JP 2017532656 A JP2017532656 A JP 2017532656A JP 2017538722 A JP2017538722 A JP 2017538722A
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- 150000003212 purines Chemical class 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
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- NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
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- 206010041232 sneezing Diseases 0.000 description 1
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- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
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- VTHOKNTVYKTUPI-UHFFFAOYSA-N triethoxy-[3-(3-triethoxysilylpropyltetrasulfanyl)propyl]silane Chemical compound CCO[Si](OCC)(OCC)CCCSSSSCCC[Si](OCC)(OCC)OCC VTHOKNTVYKTUPI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
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- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
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| US201462094418P | 2014-12-19 | 2014-12-19 | |
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| PCT/US2015/066193 WO2016100569A1 (en) | 2014-12-19 | 2015-12-16 | Substituted nucleosides, nucleotides and analogs thereof |
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| JP2023514182A (ja) * | 2020-02-18 | 2023-04-05 | ギリアード サイエンシーズ， インコーポレイテッド | 抗ウイルス化合物 |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
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| SI2794627T1 (sl) | 2011-12-22 | 2019-02-28 | Alios Biopharma, Inc. | Substituirani nukleozidi, nukleotidi in njihovi analogi |
| 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 |
| WO2013142124A1 (en) | 2012-03-21 | 2013-09-26 | Vertex Pharmaceuticals Incorporated | Solid forms of a thiophosphoramidate nucleotide prodrug |
| ES2865402T3 (es) | 2012-12-21 | 2021-10-15 | Janssen Biopharma Inc | 4'-fluoronucleósidos, 4'-fluoronucleótidos y análogos de los mismos para el tratamiento del VHC |
| EP2935305A4 (en) | 2012-12-21 | 2016-08-03 | Alios Biopharma Inc | SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGUE THEREOF |
| CA2908313A1 (en) | 2013-04-05 | 2014-10-09 | Alios Biopharma, Inc. | Hepatitis c viral infection treatment using a combination of compounds |
| TWI655199B (zh) | 2013-06-26 | 2019-04-01 | 美商艾洛斯生物製藥公司 | 經取代之核苷、核苷酸及其類似物 |
| EP3013340B9 (en) * | 2013-06-26 | 2023-10-04 | Janssen Pharmaceuticals, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| JP6562908B2 (ja) | 2013-10-11 | 2019-08-21 | ヤンセン 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の類似体 |
| AU2015280248B2 (en) | 2014-06-24 | 2021-04-08 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| NZ727582A (en) | 2014-06-24 | 2018-06-29 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| 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 |
| CN107427530B (zh) | 2015-03-06 | 2020-09-08 | 阿堤亚制药公司 | 用于HCV治疗的β-D-2’-脱氧-2’α-氟-2’-β-C-取代的-2-改性的-N6-取代的嘌呤核苷酸 |
| MX383931B (es) | 2015-03-11 | 2025-03-14 | Janssen Biopharma Inc | Compuestos de aza-piridona y usos de estos. |
| TW201718618A (zh) * | 2015-09-18 | 2017-06-01 | 田邊三菱製藥股份有限公司 | 架橋型核酸ＧｕＮＡ，其製造方法，及中間體化合物 |
| 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 |
| AU2017324939B2 (en) | 2016-09-07 | 2021-10-14 | Atea Pharmaceuticals, Inc. | 2'-substituted-N6-substituted purine nucleotides for RNA virus treatment |
| JP7125714B2 (ja) * | 2016-12-13 | 2022-08-25 | ヤマサ醤油株式会社 | 抗ウイルス活性を有する２’－デオキシ－７－デアザプリンヌクレオシド誘導体 |
| US10519186B2 (en) | 2017-02-01 | 2019-12-31 | Atea Pharmaceuticals, Inc. | Nucleotide hemi-sulfate salt for the treatment of hepatitis C virus |
| AU2018332540B2 (en) | 2017-09-18 | 2023-10-05 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| KR20200140865A (ko) | 2018-04-10 | 2020-12-16 | 아테아 파마슈티컬즈, 인크. | 간경변증을 갖는 hcv 감염 환자의 치료 |
| AU2020231934B2 (en) | 2019-03-06 | 2023-04-20 | Glaxosmithkline Intellectual Property (No.2) Limited | Compounds useful in HIV therapy |
| 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 |
| TWI883391B (zh) | 2020-02-18 | 2025-05-11 | 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 |
| WO2021188959A1 (en) | 2020-03-20 | 2021-09-23 | Gilead Sciences, Inc. | Prodrugs of 4'-c-substituted-2-halo-2'-deoxyadenosine nucleosides and methods of making and using the same |
| US12274700B1 (en) | 2020-10-30 | 2025-04-15 | Accencio LLC | Methods of treating symptoms of coronavirus infection with RNA polymerase inhibitors |
| KR20230170745A (ko) | 2021-04-16 | 2023-12-19 | 길리애드 사이언시즈, 인코포레이티드 | 아미드를 사용한 카르바뉴클레오시드를 제조하는 방법 |
| CN117500494A (zh) | 2021-06-17 | 2024-02-02 | 阿堤亚制药公司 | 有利的抗hcv联合疗法 |
| US12116380B2 (en) | 2021-08-18 | 2024-10-15 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
| US20250032527A1 (en) | 2021-11-01 | 2025-01-30 | Immunic Ag | Medical use of n4-hydroxy citicoline compounds |
| 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 |
| CN114288313B (zh) * | 2022-02-18 | 2023-07-04 | 常晓宇 | 嘧啶核苷类药物在制备预防或治疗冠状病毒感染性疾病药物中的用途 |
| TW202400134A (zh) | 2022-03-15 | 2024-01-01 | 美商羅米醫療公司 | 用於治療疾病之化合物及方法 |
Family Cites Families (41)
| 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 |
| MXPA01011517A (es) | 1999-05-12 | 2003-08-20 | Yamasa Corp | Nucleosidos de 4'-c-etinil-purina. |
| JP2004532184A (ja) | 2001-01-22 | 2004-10-21 | メルク エンド カムパニー インコーポレーテッド | Ｒｎａ依存性ｒｎａウィルスポリメラーゼ阻害薬としてのヌクレオシド誘導体 |
| GB0114286D0 (en) | 2001-06-12 | 2001-08-01 | Hoffmann La Roche | Nucleoside Derivatives |
| WO2005020884A2 (en) * | 2003-05-14 | 2005-03-10 | Idenix (Cayman) Limited | Nucleosides for treatment of infection by corona viruses, toga viruses and picorna viruses |
| CA2502109C (en) * | 2004-03-24 | 2010-02-23 | Yamasa Corporation | 4'-c-substituted-2-haloadenosine derivative |
| CN100532388C (zh) * | 2007-07-16 | 2009-08-26 | 郑州大学 | 2’-氟-4’-取代-核苷类似物、其制备方法及应用 |
| WO2009064387A2 (en) * | 2007-11-09 | 2009-05-22 | Gov't Of The U.S.A, As Represented By The Secretary, Department Of Health & Human Services | C4'-substituted-2-deoxyadenosine analogs and methods of treating hiv |
| US20090318380A1 (en) * | 2007-11-20 | 2009-12-24 | Pharmasset, Inc. | 2',4'-substituted nucleosides as antiviral agents |
| US8163707B2 (en) | 2008-09-15 | 2012-04-24 | Enanta Pharmaceuticals, Inc. | 4′-allene-substituted nucleoside derivatives |
| AP2011005929A0 (en) | 2009-03-20 | 2011-10-31 | Alios Biopharma Inc | Substituted nucleoside and nucleotide analogs. |
| CA2761880A1 (en) | 2009-05-12 | 2010-11-18 | John A. Secrist, Iii | 2'-fluoro arabino nucleosides and use thereof |
| AU2011305652B2 (en) | 2010-09-22 | 2016-10-20 | Janssen Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
| SG188497A1 (en) | 2010-09-22 | 2013-05-31 | Alios Biopharma Inc | Substituted nucleotide analogs |
| WO2012040126A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| EP2655392B1 (en) | 2010-12-22 | 2018-04-18 | Alios Biopharma, Inc. | Cyclic nucleotide analogs |
| EP2794630A4 (en) | 2011-12-22 | 2015-04-01 | Alios Biopharma Inc | SUBSTITUTED PHOSPHORTHIOAT NUCLEOTIDE ANALOGUE |
| SI2794627T1 (sl) | 2011-12-22 | 2019-02-28 | Alios Biopharma, Inc. | Substituirani nukleozidi, nukleotidi in njihovi analogi |
| WO2013142159A1 (en) | 2012-03-21 | 2013-09-26 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| WO2013142124A1 (en) | 2012-03-21 | 2013-09-26 | Vertex Pharmaceuticals Incorporated | Solid forms of a thiophosphoramidate nucleotide prodrug |
| EP2828278A4 (en) | 2012-03-21 | 2015-12-09 | Alios Biopharma Inc | PROCESSES FOR PREPARING SUBSTITUTED NUCLEOTIDE ANALOGS |
| ME03502B (me) | 2012-03-21 | 2020-04-20 | Janssen Biopharma Inc | Supstituisani nukleozidi, nukleotidi i njihovi analozi |
| HK1203356A1 (en) | 2012-03-22 | 2015-10-30 | 艾丽奥斯生物制药有限公司 | Pharmaceutical combinations comprising a thionucleotide analog |
| EP2935305A4 (en) | 2012-12-21 | 2016-08-03 | Alios Biopharma Inc | SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGUE THEREOF |
| ES2865402T3 (es) | 2012-12-21 | 2021-10-15 | Janssen Biopharma Inc | 4'-fluoronucleósidos, 4'-fluoronucleótidos y análogos de los mismos para el tratamiento del VHC |
| US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
| US20140309413A1 (en) | 2013-03-11 | 2014-10-16 | 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 |
| EP3013340B9 (en) | 2013-06-26 | 2023-10-04 | Janssen Pharmaceuticals, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| TWI655199B (zh) | 2013-06-26 | 2019-04-01 | 美商艾洛斯生物製藥公司 | 經取代之核苷、核苷酸及其類似物 |
| JP6562908B2 (ja) | 2013-10-11 | 2019-08-21 | ヤンセン 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の類似体 |
| PH12016501567B1 (en) * | 2014-02-06 | 2023-12-06 | Riboscience Llc | 4`-difluoromethyl substituted nucleoside derivatives as inhibitors of influenza rna replication |
| WO2015143712A1 (en) * | 2014-03-28 | 2015-10-01 | Merck Sharp & Dohme Corp. | 4'-substituted nucleoside reverse transcriptase inhibitors |
| AU2015280248B2 (en) * | 2014-06-24 | 2021-04-08 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| CA2952812A1 (en) | 2014-06-24 | 2015-12-30 | Alios Biopharma, Inc. | Methods of preparing substituted nucleotide analogs |
| NZ727582A (en) | 2014-06-24 | 2018-06-29 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| JP2017525681A (ja) | 2014-07-22 | 2017-09-07 | アリオス バイオファーマ インク． | パラミクソウイルスの治療方法 |
| SG11201700851WA (en) | 2014-08-05 | 2017-03-30 | 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 |
-
2015
- 2015-12-15 MA MA041213A patent/MA41213A/fr unknown
- 2015-12-16 AU AU2015364630A patent/AU2015364630A1/en not_active Abandoned
- 2015-12-16 JP JP2017532656A patent/JP2017538722A/ja not_active Withdrawn
- 2015-12-16 WO PCT/US2015/066193 patent/WO2016100569A1/en not_active Ceased
- 2015-12-16 MX MX2017008184A patent/MX2017008184A/es unknown
- 2015-12-16 EP EP15871022.8A patent/EP3233879A4/en not_active Withdrawn
- 2015-12-16 HK HK18105072.0A patent/HK1245800A1/zh unknown
- 2015-12-16 CA CA2970936A patent/CA2970936A1/en not_active Abandoned
- 2015-12-16 US US14/971,926 patent/US9890188B2/en not_active Expired - Fee Related
- 2015-12-16 CN CN201580076647.5A patent/CN107250145A/zh active Pending
- 2015-12-18 TW TW104142822A patent/TW201625658A/zh unknown
-
2017
- 2017-07-18 ZA ZA2017/04876A patent/ZA201704876B/en unknown
-
2018
- 2018-01-30 US US15/884,052 patent/US20180155384A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023514182A (ja) * | 2020-02-18 | 2023-04-05 | ギリアード サイエンシーズ， インコーポレイテッド | 抗ウイルス化合物 |
| JP7429799B2 (ja) | 2020-02-18 | 2024-02-08 | ギリアード サイエンシーズ， インコーポレイテッド | 抗ウイルス化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1245800A1 (zh) | 2018-08-31 |
| EP3233879A4 (en) | 2018-09-19 |
| ZA201704876B (en) | 2020-01-29 |
| CN107250145A (zh) | 2017-10-13 |
| US20160176910A1 (en) | 2016-06-23 |
| AU2015364630A1 (en) | 2017-07-06 |
| EP3233879A1 (en) | 2017-10-25 |
| WO2016100569A1 (en) | 2016-06-23 |
| US9890188B2 (en) | 2018-02-13 |
| MA41213A (fr) | 2017-10-24 |
| TW201625658A (zh) | 2016-07-16 |
| CA2970936A1 (en) | 2016-06-23 |
| MX2017008184A (es) | 2018-03-06 |
| US20180155384A1 (en) | 2018-06-07 |
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