EA015178B1 - Противовирусные производные пиримидиновых нуклеозидов - Google Patents
Противовирусные производные пиримидиновых нуклеозидов Download PDFInfo
- Publication number
- EA015178B1 EA015178B1 EA200870505A EA200870505A EA015178B1 EA 015178 B1 EA015178 B1 EA 015178B1 EA 200870505 A EA200870505 A EA 200870505A EA 200870505 A EA200870505 A EA 200870505A EA 015178 B1 EA015178 B1 EA 015178B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- compound according
- valine
- alkyl
- pharmaceutically acceptable
- Prior art date
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Classifications
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
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- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- C—CHEMISTRY; METALLURGY
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- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—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
- A61K31/7064—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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
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| GBGB0609178.9A GB0609178D0 (en) | 2006-05-09 | 2006-05-09 | Novel compounds |
| PCT/GB2007/001677 WO2007129083A1 (en) | 2006-05-09 | 2007-05-09 | Anti-viral pyrimidine nucleoside derivatives |
Publications (2)
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| EA200870505A1 EA200870505A1 (ru) | 2009-04-28 |
| EA015178B1 true EA015178B1 (ru) | 2011-06-30 |
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| EA200870505A EA015178B1 (ru) | 2006-05-09 | 2007-05-09 | Противовирусные производные пиримидиновых нуклеозидов |
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| IL (1) | IL194806A (enExample) |
| NZ (1) | NZ573377A (enExample) |
| PL (1) | PL2016081T3 (enExample) |
| PT (1) | PT2016081E (enExample) |
| SI (1) | SI2016081T1 (enExample) |
| TW (1) | TWI385172B (enExample) |
| WO (1) | WO2007129083A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0009486D0 (en) * | 2000-04-17 | 2000-06-07 | Univ Cardiff | Chemical compounds |
| GB2452556A (en) * | 2007-09-07 | 2009-03-11 | Univ Leuven Kath | Nucleoside analogues esterified at 3 and/or 5 positions by neutral non-polar amino acid, or oligopeptide thereof, for combating Varicella Zoster virus |
| JP2013539760A (ja) * | 2010-10-09 | 2013-10-28 | シナジー ファーマシューティカルズ インコーポレイテッド | 抗ウイルス化合物およびその有用な中間体の調製方法 |
| CN102443032B (zh) * | 2010-10-09 | 2015-07-22 | 英希比泰克斯公司 | 制备抗病毒组合物的方法及其中间体的应用 |
| MD4110C1 (ro) * | 2010-10-21 | 2011-12-31 | Валериу РУДИК | Preparat antiherpetiс |
| KR101875997B1 (ko) * | 2015-05-04 | 2018-07-06 | 엔 앤드 엔 파마세우티칼스 인크. | 엔-메탄노카르바티미딘을 이용한 대상포진의 치료방법 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010018440A1 (en) * | 1996-11-15 | 2001-08-30 | Yale University And The University Of Georgia Research Foundation, Inc. | L-beta-dioxolane uridine analogs and methods for treating and preventing virus infections |
| WO2001083501A1 (en) * | 2000-04-17 | 2001-11-08 | University College Cardiff Consultants Limited | Anti-viral pyrimidine nucleoside analogues |
| WO2001085749A1 (en) * | 2000-05-09 | 2001-11-15 | University College Cardiff Consultants Limited | Anti-viral pyrimidine nucleoside analogues |
Family Cites Families (15)
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| JPS62255499A (ja) | 1986-04-28 | 1987-11-07 | Teijin Ltd | 螢光性ヌクレオシド又はヌクレオチド |
| EP0346108A3 (en) | 1988-06-09 | 1991-04-24 | The Wellcome Foundation Limited | Anti-infective nucleosides |
| YU43193A (sh) | 1992-06-22 | 1997-01-08 | Eli Lilly And Company | 2'-deoksi-2',2'-difluoro(4-supstituisani)pirimidinski nukleozidi antivirusnog i antikancerogenog dejstva i međuproizvodi |
| GB9505025D0 (en) | 1995-03-13 | 1995-05-03 | Medical Res Council | Chemical compounds |
| GB9708611D0 (en) | 1997-04-28 | 1997-06-18 | Univ Cardiff | Chemical compounds |
| GB9716231D0 (en) | 1997-07-31 | 1997-10-08 | Amersham Int Ltd | Base analogues |
| HK1053126A1 (zh) | 1999-07-22 | 2003-10-10 | 新生物生物公司 | 酶催化的治疗活化 |
| IL147749A0 (en) | 1999-07-22 | 2002-08-14 | Newbiotics Inc | Methods for treating therapy-resistant tumors |
| JP2003527317A (ja) | 1999-07-22 | 2003-09-16 | ニューバイオティックス インコーポレイテッド | 酵素触媒抗感染性治療剤 |
| MY141594A (en) * | 2000-06-15 | 2010-05-14 | Novirio Pharmaceuticals Ltd | 3'-PRODRUGS OF 2'-DEOXY-ß-L-NUCLEOSIDES |
| US6875751B2 (en) * | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| AU2003247084B9 (en) * | 2002-06-28 | 2018-07-26 | Centre National De La Recherche Scientifique | Modified 2' and 3'-nucleoside prodrugs for treating flaviridae infections |
| US7582748B2 (en) * | 2003-03-20 | 2009-09-01 | Microbiologica Quimica E Farmaceutical Ltd. | Methods of manufacture of 2′-deoxy-β-L-nucleosides |
| US20050137141A1 (en) | 2003-10-24 | 2005-06-23 | John Hilfinger | Prodrug composition |
| AU2004320625B2 (en) | 2004-06-07 | 2009-08-27 | Anadys Pharmaceuticals, Inc. | 3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and uses thereof |
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2006
- 2006-05-09 GB GBGB0609178.9A patent/GB0609178D0/en not_active Ceased
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2007
- 2007-05-09 BR BRPI0711354-4A patent/BRPI0711354A2/pt not_active IP Right Cessation
- 2007-05-09 CN CN2007800169982A patent/CN101443332B/zh not_active Expired - Fee Related
- 2007-05-09 ES ES07732706T patent/ES2365057T3/es active Active
- 2007-05-09 DK DK07732706.2T patent/DK2016081T3/da active
- 2007-05-09 JP JP2009508479A patent/JP5261374B2/ja not_active Expired - Fee Related
- 2007-05-09 PL PL07732706T patent/PL2016081T3/pl unknown
- 2007-05-09 AT AT07732706T patent/ATE506367T1/de active
- 2007-05-09 WO PCT/GB2007/001677 patent/WO2007129083A1/en not_active Ceased
- 2007-05-09 KR KR1020087029280A patent/KR101447522B1/ko not_active Expired - Fee Related
- 2007-05-09 NZ NZ573377A patent/NZ573377A/en not_active IP Right Cessation
- 2007-05-09 PT PT07732706T patent/PT2016081E/pt unknown
- 2007-05-09 SI SI200730661T patent/SI2016081T1/sl unknown
- 2007-05-09 AU AU2007246814A patent/AU2007246814B2/en not_active Ceased
- 2007-05-09 US US12/226,044 patent/US8329664B2/en not_active Expired - Fee Related
- 2007-05-09 EA EA200870505A patent/EA015178B1/ru not_active IP Right Cessation
- 2007-05-09 CA CA 2656780 patent/CA2656780C/en not_active Expired - Fee Related
- 2007-05-09 TW TW096116477A patent/TWI385172B/zh not_active IP Right Cessation
- 2007-05-09 EP EP07732706A patent/EP2016081B1/en not_active Not-in-force
- 2007-05-09 DE DE602007014030T patent/DE602007014030D1/de active Active
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2008
- 2008-10-22 IL IL194806A patent/IL194806A/en active IP Right Grant
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2011
- 2011-07-15 CY CY20111100693T patent/CY1111711T1/el unknown
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2012
- 2012-11-30 US US13/690,794 patent/US8859512B2/en not_active Expired - Fee Related
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2014
- 2014-09-10 US US14/482,125 patent/US9427447B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010018440A1 (en) * | 1996-11-15 | 2001-08-30 | Yale University And The University Of Georgia Research Foundation, Inc. | L-beta-dioxolane uridine analogs and methods for treating and preventing virus infections |
| WO2001083501A1 (en) * | 2000-04-17 | 2001-11-08 | University College Cardiff Consultants Limited | Anti-viral pyrimidine nucleoside analogues |
| WO2001085749A1 (en) * | 2000-05-09 | 2001-11-15 | University College Cardiff Consultants Limited | Anti-viral pyrimidine nucleoside analogues |
Non-Patent Citations (2)
| Title |
|---|
| ANGELL A. ET AL.: "Bicyclic anti-VZV nucleosides: thieno analogues bearing an alkylphenyl side chain have reduced antiviral activity" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 14, no. 10, 17 May 2004 (2004-05-17), pages 2397-2399, XP004841208 ISSN: 0960-894X page 2398, column 1, paragraph 3 page 2398; table 1 * |
| MCGUIGAN S. ET AL.: "Phosphoramidate derivatives of d4T with improved anti-HIV efficacy retain full activity in thymidine kinase-deficient cells" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 6, no. 10, 21 May 1996 (1996-05-21), pages 1183-1186, XP004134894 ISSN: 0960-894X Scheme page 1184 * |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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