AU2018284131B2 - Synthesis of substantially diastereomerically pure phosphate protides - Google Patents

Synthesis of substantially diastereomerically pure phosphate protides Download PDF

Info

Publication number
AU2018284131B2
AU2018284131B2 AU2018284131A AU2018284131A AU2018284131B2 AU 2018284131 B2 AU2018284131 B2 AU 2018284131B2 AU 2018284131 A AU2018284131 A AU 2018284131A AU 2018284131 A AU2018284131 A AU 2018284131A AU 2018284131 B2 AU2018284131 B2 AU 2018284131B2
Authority
AU
Australia
Prior art keywords
compound
diastereoisomer
formula
mixture
formula ila
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.)
Active
Application number
AU2018284131A
Other languages
English (en)
Other versions
AU2018284131A1 (en
Inventor
Venkata Lakshmi Narasimha Rao Dammalapati
Hugh GRIFFITH
Gordon KENNOVIN
Mani Bushan KOTALA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nucana PLC
Original Assignee
Nucana PLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Nucana PLC filed Critical Nucana PLC
Publication of AU2018284131A1 publication Critical patent/AU2018284131A1/en
Application granted granted Critical
Publication of AU2018284131B2 publication Critical patent/AU2018284131B2/en
Priority to AU2022204691A priority Critical patent/AU2022204691B2/en
Priority to AU2024200428A priority patent/AU2024200428B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
    • 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
    • C07H19/16—Purine radicals
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/02—Phosphorylation
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
AU2018284131A 2017-06-14 2018-06-14 Synthesis of substantially diastereomerically pure phosphate protides Active AU2018284131B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2022204691A AU2022204691B2 (en) 2017-06-14 2022-06-30 Synthesis of substantially diastereomerically pure phosphate protides
AU2024200428A AU2024200428B2 (en) 2017-06-14 2024-01-24 Synthesis of substantially diastereomerically pure phosphate protides

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB1709471.5 2017-06-14
GBGB1709471.5A GB201709471D0 (en) 2017-06-14 2017-06-14 Diastereoselective synthesis of hosphate derivatives
PCT/GB2018/051638 WO2018229493A2 (en) 2017-06-14 2018-06-14 Synthesis of phosphate derivatives

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2022204691A Division AU2022204691B2 (en) 2017-06-14 2022-06-30 Synthesis of substantially diastereomerically pure phosphate protides

Publications (2)

Publication Number Publication Date
AU2018284131A1 AU2018284131A1 (en) 2020-01-16
AU2018284131B2 true AU2018284131B2 (en) 2022-04-07

Family

ID=59358400

Family Applications (3)

Application Number Title Priority Date Filing Date
AU2018284131A Active AU2018284131B2 (en) 2017-06-14 2018-06-14 Synthesis of substantially diastereomerically pure phosphate protides
AU2022204691A Active AU2022204691B2 (en) 2017-06-14 2022-06-30 Synthesis of substantially diastereomerically pure phosphate protides
AU2024200428A Active AU2024200428B2 (en) 2017-06-14 2024-01-24 Synthesis of substantially diastereomerically pure phosphate protides

Family Applications After (2)

Application Number Title Priority Date Filing Date
AU2022204691A Active AU2022204691B2 (en) 2017-06-14 2022-06-30 Synthesis of substantially diastereomerically pure phosphate protides
AU2024200428A Active AU2024200428B2 (en) 2017-06-14 2024-01-24 Synthesis of substantially diastereomerically pure phosphate protides

Country Status (18)

Country Link
US (4) US11414452B2 (enExample)
EP (2) EP3638685A1 (enExample)
JP (4) JP7279991B2 (enExample)
KR (2) KR20240127483A (enExample)
CN (3) CN110785425B (enExample)
AU (3) AU2018284131B2 (enExample)
BR (1) BR112019026747A2 (enExample)
CA (2) CA3064177A1 (enExample)
CL (1) CL2019003632A1 (enExample)
EA (1) EA201992873A1 (enExample)
GB (1) GB201709471D0 (enExample)
IL (3) IL302559B2 (enExample)
MA (1) MA49379A (enExample)
MX (3) MX391332B (enExample)
PH (1) PH12019502825A1 (enExample)
SA (1) SA519410795B1 (enExample)
SG (1) SG11201911543UA (enExample)
WO (2) WO2018229495A1 (enExample)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2681227T1 (sl) 2011-03-01 2016-04-29 Nucana Biomed Limited Fosforamidatni derivati 5-fluoro-2'-deoksiuridina za uporabo pri zdravljenju raka
EA033046B1 (ru) 2014-06-25 2019-08-30 НУКАНА ПиЭлСи Состав, содержащий пролекарство гемцитабина
EP3683225A1 (en) 2014-11-28 2020-07-22 Nucana PLC New 2' and/or 5' amino-acid ester phosphoramidate 3'-deoxy adenosine derivatives as anti-cancer compounds
SG11201804774YA (en) 2015-12-11 2018-07-30 NuCana plc Diastereoselective synthesis of phosphate derivatives and of the gemcitabine prodrug nuc-1031
GB201522764D0 (en) 2015-12-23 2016-02-03 Nucana Biomed Ltd Formulations of phosphate derivatives
GB201609600D0 (en) 2016-06-01 2016-07-13 Nucuna Biomed Ltd Cancer treatments
GB201709471D0 (en) * 2017-06-14 2017-07-26 Nucana Biomed Ltd Diastereoselective synthesis of hosphate derivatives
GB201715011D0 (en) 2017-09-18 2017-11-01 Nucana Biomed Ltd Floxuridine synthesis
CN112409421A (zh) * 2020-12-01 2021-02-26 上海兆维科技发展有限公司 一种3’-磷酸酯核苷的制备方法
CN119546313A (zh) 2022-05-12 2025-02-28 努卡那有限公司 使用nuc-7738的癌症治疗
WO2024121527A1 (en) 2022-12-07 2024-06-13 NuCana plc Synthesis of nucleoside derivative nuc-3373

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016030335A1 (en) * 2014-08-25 2016-03-03 Medivir Ab Dioxolane analogues of uridine for the treatment of cancer
WO2016083830A1 (en) * 2014-11-28 2016-06-02 Nucana Biomed Limited New 2' and/or 5' amino-acid ester phosphoramidate 3'-deoxy adenosine derivatives as anti-cancer compounds
WO2016098123A2 (en) * 2014-12-16 2016-06-23 Laurus Labs Private Ltd A recycling process for preparing (s)-2-[(substituted-phenoxy)-phenoxy- phosphorylamino] propionic acid isopropyl ester diastereomers
WO2017207989A1 (en) * 2016-06-01 2017-12-07 Nucana Biomed Limited Adenosine derivatives for use in the treatment of cancer

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE279248C (enExample)
US3792039A (en) 1971-12-27 1974-02-12 Miles Lab Poly 2'-fluoro-2'-deoxyuridylic acid
US4500707A (en) * 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4357324A (en) 1981-02-24 1982-11-02 The United States Of America As Represented By The Department Of Health And Human Services Prodrug derivatives of 9β-D-arabinofuranosyl-2-fluoroadenine
US4668777A (en) * 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US7462605B2 (en) 1998-01-23 2008-12-09 Celmed Oncology (Usa), Inc. Phosphoramidate compounds and methods of use
IL137164A0 (en) 1998-01-23 2001-07-24 Newbiotics Inc Enzyme catalyzed therapeutic agents
US6683061B1 (en) 1999-07-22 2004-01-27 Newbiotics, Inc. Enzyme catalyzed therapeutic activation
GB0317009D0 (en) 2003-07-21 2003-08-27 Univ Cardiff Chemical compounds
EP1827460A4 (en) 2004-12-09 2012-03-14 Univ Minnesota NUCLEOSIDE WITH ANTIVIRAL AND ANTI-CANCER EFFECT
GB0505781D0 (en) 2005-03-21 2005-04-27 Univ Cardiff Chemical compounds
CA2618335C (en) 2005-08-15 2015-03-31 F.Hoffmann-La Roche Ag Antiviral phosphoramidates of 4'-substituted pronucleotides
GB0623493D0 (en) 2006-11-24 2007-01-03 Univ Cardiff Chemical compounds
US7951789B2 (en) * 2006-12-28 2011-05-31 Idenix Pharmaceuticals, Inc. Compounds and pharmaceutical compositions for the treatment of viral infections
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
US20090206007A1 (en) 2008-02-20 2009-08-20 Air Products And Chemicals, Inc. Process and apparatus for upgrading coal using supercritical water
JP2012514657A (ja) 2009-01-09 2012-06-28 ユニバーシテイ・カレツジ・オブ・カーデイフ・コンサルタンツ・リミテツド ウィルス感染を治療するためのグアノシンヌクレオシド化合物のホスホルアミダート誘導体
EP2623104A1 (en) 2009-03-20 2013-08-07 Alios Biopharma, Inc. Substituted nucleoside and nucleotide analogs
TWI598358B (zh) 2009-05-20 2017-09-11 基利法瑪席特有限責任公司 核苷磷醯胺
US8618076B2 (en) 2009-05-20 2013-12-31 Gilead Pharmasset Llc Nucleoside phosphoramidates
JP2013527145A (ja) 2010-03-31 2013-06-27 ギリード・ファーマセット・エルエルシー リン含有活性化剤の立体選択的合成
TW201136945A (en) 2010-03-31 2011-11-01 Pharmasset Inc Purine nucleoside phosphoramidate
NZ606141A (en) 2010-07-19 2015-03-27 Gilead Sciences Inc Methods for the preparation of diasteromerically pure phosphoramidate prodrugs
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
PT3042910T (pt) 2010-11-30 2019-04-16 Gilead Pharmasset Llc 2'-espiro-nucleósidos para utilização na terapia da hepatite c
AU2011349278C1 (en) 2010-12-22 2017-01-19 Alios Biopharma, Inc. Cyclic nucleotide analogs
SI2681227T1 (sl) 2011-03-01 2016-04-29 Nucana Biomed Limited Fosforamidatni derivati 5-fluoro-2'-deoksiuridina za uporabo pri zdravljenju raka
EP2890704B1 (en) * 2012-08-31 2018-02-28 Novartis AG 2'-ethynyl nucleoside derivatives for treatment of viral infections
CN104903339A (zh) 2012-11-16 2015-09-09 卡迪夫大学学院顾问有限公司 用于制备核苷前体药物的方法
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
WO2015081133A2 (en) 2013-11-27 2015-06-04 Idenix Pharmaceuticals, Inc. Nucleotides for the treatment of liver cancer
CZ307789B6 (cs) 2014-04-15 2019-05-09 Zentiva, K.S. Způsob výroby biologicky účinných fosforamidátových léčiv
EP3131914B1 (en) * 2014-04-16 2023-05-10 Idenix Pharmaceuticals LLC 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv
PL3160978T3 (pl) 2014-06-25 2020-11-30 NuCana plc Proleki gemcytabiny
EA033046B1 (ru) 2014-06-25 2019-08-30 НУКАНА ПиЭлСи Состав, содержащий пролекарство гемцитабина
JP6646663B2 (ja) 2014-07-22 2020-02-14 ニューカナ バイオメッド リミテッドＮｕｃａｎａ Ｂｉｏｍｅｄ Ｌｉｍｉｔｅｄ ゲムシタビン−［フェニル（ベンゾキシ−ｌ−アラニニル）］ホスフェートの製造方法リン酸誘導体を製造する方法
GB201417644D0 (en) 2014-10-06 2014-11-19 Nucana Biomed Ltd Method of separating phosphate diastereoisomers
CN105646629A (zh) 2014-11-25 2016-06-08 广州市恒诺康医药科技有限公司 L-核苷类化合物及其应用
WO2016145142A1 (en) 2015-03-10 2016-09-15 Emory University Nucleotide and nucleoside therapeutics compositions and uses related thereto
KR20180021697A (ko) 2015-05-14 2018-03-05 뉴카나 피엘씨 암 치료
CN106543252A (zh) 2015-09-16 2017-03-29 博瑞生物医药（苏州）股份有限公司 核苷氨基磷酸酯类前药的制备方法及其中间体
CN106543220A (zh) 2015-09-16 2017-03-29 博瑞生物医药（苏州）股份有限公司 氨基磷酸酯化合物及其制备方法和晶体
CN112156102B (zh) 2015-09-16 2023-10-03 济南高合医疗科技有限公司 一种nuc-1031单一异构体的晶型及其制备方法
WO2017060661A1 (en) 2015-10-05 2017-04-13 Nucana Biomed Limited Combination therapy
CN108431016A (zh) * 2015-11-16 2018-08-21 艾可瑞恩治疗公司 核酸前体药物
SG11201804774YA (en) 2015-12-11 2018-07-30 NuCana plc Diastereoselective synthesis of phosphate derivatives and of the gemcitabine prodrug nuc-1031
CA3008749C (en) 2015-12-23 2024-01-02 NuCana plc Treatment of ovarian cancer or biliary tract cancer with a combination of gemcitabine-(phenyl-benzoxy-l-alaninyl)]-phosphate and cisplatin
GB201522764D0 (en) 2015-12-23 2016-02-03 Nucana Biomed Ltd Formulations of phosphate derivatives
GB201609600D0 (en) 2016-06-01 2016-07-13 Nucuna Biomed Ltd Cancer treatments
GB201609601D0 (en) 2016-06-01 2016-07-13 Nucana Biomed Ltd Phosphoramidate compounds
GB201709471D0 (en) * 2017-06-14 2017-07-26 Nucana Biomed Ltd Diastereoselective synthesis of hosphate derivatives
GB201713916D0 (en) 2017-08-30 2017-10-11 Nucana Biomed Ltd Treatment regimens

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016030335A1 (en) * 2014-08-25 2016-03-03 Medivir Ab Dioxolane analogues of uridine for the treatment of cancer
WO2016083830A1 (en) * 2014-11-28 2016-06-02 Nucana Biomed Limited New 2' and/or 5' amino-acid ester phosphoramidate 3'-deoxy adenosine derivatives as anti-cancer compounds
WO2016098123A2 (en) * 2014-12-16 2016-06-23 Laurus Labs Private Ltd A recycling process for preparing (s)-2-[(substituted-phenoxy)-phenoxy- phosphorylamino] propionic acid isopropyl ester diastereomers
WO2017207989A1 (en) * 2016-06-01 2017-12-07 Nucana Biomed Limited Adenosine derivatives for use in the treatment of cancer

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
McGuigan, C. et al.; J. Med. Chem., 54, 7247-7258 (2011). DOI: 10.1021/jm200815w. *
Ross, B. S. et al.; J. Org. Chem., 76, 8311-8319 (2011). DOI:10.1021/jo201492m. *
Serpi, M. et al.; ChemistryOpen, 6, 424-436 (2017). DOI: 10.1002/open.201700019. *
Simmons, B. et al.; Org. Lett., 19, 2218-2221 (2017). DOI: 10.1021/acs.orglett.7b00469. *

Also Published As

Publication number Publication date
IL312228B2 (en) 2025-06-01
WO2018229493A2 (en) 2018-12-20
US12054511B2 (en) 2024-08-06
US20200181186A1 (en) 2020-06-11
GB201709471D0 (en) 2017-07-26
CA3064177A1 (en) 2018-12-20
CN110753697A (zh) 2020-02-04
CA3065682A1 (en) 2018-12-20
CN110753697B (zh) 2023-10-13
US20200181190A1 (en) 2020-06-11
KR102695300B1 (ko) 2024-08-16
SA519410795B1 (ar) 2023-11-19
KR20200016864A (ko) 2020-02-17
MX390901B (es) 2025-03-21
WO2018229493A3 (en) 2019-02-07
AU2024200428A1 (en) 2024-02-08
US11414452B2 (en) 2022-08-16
IL271159A (en) 2020-01-30
IL312228B1 (en) 2025-02-01
IL312228A (en) 2024-06-01
EP3638684A2 (en) 2020-04-22
CN110785425A (zh) 2020-02-11
MX2019014907A (es) 2020-02-13
MX2019014914A (es) 2020-02-13
JP2020523381A (ja) 2020-08-06
US11897913B2 (en) 2024-02-13
CN117486959A (zh) 2024-02-02
MX391332B (es) 2025-03-21
IL302559B2 (en) 2024-09-01
MX2022003822A (es) 2022-05-25
CN110785425B (zh) 2023-11-21
IL302559B1 (en) 2024-05-01
KR20240127483A (ko) 2024-08-22
JP2023095954A (ja) 2023-07-06
US20250171487A1 (en) 2025-05-29
EP3638685A1 (en) 2020-04-22
AU2022204691A1 (en) 2022-08-04
IL302559A (en) 2023-07-01
IL271159B1 (en) 2023-06-01
JP2020523378A (ja) 2020-08-06
JP7248209B2 (ja) 2023-03-29
JP7279991B2 (ja) 2023-05-23
JP2024138523A (ja) 2024-10-08
JP7525687B2 (ja) 2024-07-30
US20220402962A1 (en) 2022-12-22
SG11201911543UA (en) 2020-01-30
EA201992873A1 (ru) 2020-05-19
IL271159B2 (en) 2023-10-01
AU2022204691B2 (en) 2023-11-23
MA49379A (fr) 2020-04-22
PH12019502825A1 (en) 2020-10-26
AU2018284131A1 (en) 2020-01-16
BR112019026747A2 (pt) 2020-06-30
CL2019003632A1 (es) 2020-08-14
WO2018229495A1 (en) 2018-12-20
AU2024200428B2 (en) 2025-10-16

Similar Documents

Publication Publication Date Title
AU2022204691B2 (en) Synthesis of substantially diastereomerically pure phosphate protides
AU2016367237B2 (en) Diastereoselective synthesis of phosphate derivatives and of the gemcitabine prodrug NUC-1031
EP3172218B1 (en) Process for the preparation of gemcitabine-[phenyl(benzoxy-l-alaninyl)] phosphate
EP3684780B1 (en) Floxuridine synthesis
EA043691B1 (ru) Получение фосфатных производных
EA047265B1 (ru) Получение фосфатных производных
HK1232546B (en) Process for the preparation of gemcitabine-[phenyl(benzoxy-l-alaninyl)] phosphate
HK1232546A1 (en) Process for the preparation of gemcitabine-[phenyl(benzoxy-l-alaninyl)] phosphate

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)