CN109689065A - 用于治疗乙型肝炎病毒的磷酰胺化物 - Google Patents

用于治疗乙型肝炎病毒的磷酰胺化物 Download PDF

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Publication number
CN109689065A
CN109689065A CN201780050071.4A CN201780050071A CN109689065A CN 109689065 A CN109689065 A CN 109689065A CN 201780050071 A CN201780050071 A CN 201780050071A CN 109689065 A CN109689065 A CN 109689065A
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substituted
alkyl
amino
alkenyl
alkynyl
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亚伯·德拉罗莎
乔治·佩因特
格雷戈里·R·布鲁姆林
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Emory University
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Emory University
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    • 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
    • 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
    • A61K31/7072—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 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • A61K31/52—Purines, e.g. adenine
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    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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    • 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
    • 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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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
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  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Materials For Medical Uses (AREA)
CN201780050071.4A 2016-06-24 2017-06-23 用于治疗乙型肝炎病毒的磷酰胺化物 Pending CN109689065A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662354471P 2016-06-24 2016-06-24
US62/354,471 2016-06-24
PCT/US2017/038963 WO2017223421A1 (en) 2016-06-24 2017-06-23 Phosphoramidates for the treatment of hepatitis b virus

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CN109689065A true CN109689065A (zh) 2019-04-26

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US (2) US11364257B2 (https=)
EP (1) EP3474863A4 (https=)
JP (2) JP2019525905A (https=)
KR (1) KR20190057277A (https=)
CN (1) CN109689065A (https=)
AU (1) AU2017281531A1 (https=)
BR (1) BR112018076913A2 (https=)
CA (1) CA3029315A1 (https=)
EA (1) EA201990059A1 (https=)
IL (1) IL263859B2 (https=)
PH (1) PH12018550207A1 (https=)
SG (1) SG11201811316YA (https=)
WO (1) WO2017223421A1 (https=)
ZA (1) ZA201900156B (https=)

Cited By (7)

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Publication number Priority date Publication date Assignee Title
CN110642910A (zh) * 2019-09-02 2020-01-03 南开大学 胸苷衍生物及其制备方法和用途
CN111087421A (zh) * 2019-12-24 2020-05-01 南京正大天晴制药有限公司 一种用于手性药物合成的磷酰胺化合物的制备方法
WO2021204059A1 (zh) * 2020-04-08 2021-10-14 北京君科华元医药科技有限公司 单磷酸恩替卡韦丙氨酰胺酚酯及其医药用途
CN113501853A (zh) * 2021-09-13 2021-10-15 南京颐媛生物医学研究院有限公司 4-硫代尿嘧啶脱氧核苷磷酸酯及其抗病毒药物用途
WO2021253376A1 (zh) * 2020-06-19 2021-12-23 南京正大天晴制药有限公司 一种用于手性药物合成的磷酰胺化合物的制备方法
CN115260263A (zh) * 2022-05-23 2022-11-01 深圳扬厉医药技术有限公司 烷基硫芳基克拉夫定磷酰胺类化合物及其应用
CN115715190A (zh) * 2020-04-02 2023-02-24 密歇根大学董事会 用于治疗病毒感染的瑞德西韦和瑞德西韦类似物、溶液剂以及纳米粒子、脂质体和微粒组合物

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US11628182B2 (en) * 2018-04-12 2023-04-18 Zogenix Mds, Inc. Prodrugs of deoxynucleosides for treatment of diseases cased by unbalanced nucleotide pools
WO2020045628A1 (ja) * 2018-08-31 2020-03-05 ダイキン工業株式会社 核酸アナログ及び抗ｂ型肝炎ウイルス剤
US11166976B2 (en) 2018-11-08 2021-11-09 Aligos Therapeutics, Inc. S-antigen transport inhibiting oligonucleotide polymers and methods
WO2020103929A1 (zh) * 2018-11-23 2020-05-28 正大天晴药业集团股份有限公司 低聚核苷酸及前体药物
CN114206896B (zh) 2019-07-17 2024-12-17 纽科利制药公司 环状脱氧核糖核苷酸化合物
WO2021067480A1 (en) * 2019-10-02 2021-04-08 University Of Washington Compositions and methods for treatment of hepatitis b virus infection
US12552820B2 (en) 2020-04-21 2026-02-17 Ligand Pharmaceuticals Incorporated Benzyloxy phosph(on)ate compounds
WO2022251594A1 (en) * 2021-05-27 2022-12-01 Antios Therapeutics, Inc. Pharmacokinetics and dose-related improvments in subjects treated with phosphoramidate clevudine prodrugs
WO2022256490A2 (en) * 2021-06-03 2022-12-08 Antios Therapeutics, Inc. Improved synthesis of phosphoramidates for the treatment of hepatitis b virus
CA3243401A1 (en) * 2022-01-28 2023-08-03 Glaxosmithkline Intellectual Property Development Limited Polytherapy for the treatment of hepatitis B virus infections

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110642910A (zh) * 2019-09-02 2020-01-03 南开大学 胸苷衍生物及其制备方法和用途
CN110642910B (zh) * 2019-09-02 2020-10-30 南开大学 胸苷衍生物及其制备方法和用途
CN111087421A (zh) * 2019-12-24 2020-05-01 南京正大天晴制药有限公司 一种用于手性药物合成的磷酰胺化合物的制备方法
CN111087421B (zh) * 2019-12-24 2022-10-18 南京正大天晴制药有限公司 一种用于手性药物合成的磷酰胺化合物的制备方法
CN115715190A (zh) * 2020-04-02 2023-02-24 密歇根大学董事会 用于治疗病毒感染的瑞德西韦和瑞德西韦类似物、溶液剂以及纳米粒子、脂质体和微粒组合物
WO2021204059A1 (zh) * 2020-04-08 2021-10-14 北京君科华元医药科技有限公司 单磷酸恩替卡韦丙氨酰胺酚酯及其医药用途
US12590097B2 (en) 2020-04-08 2026-03-31 Beijing Junke Huayuan Med Tech Co., Ltd. Substituted entecavir monophosphate alaninamide phenolic esters for resisting hepatitis b virus
WO2021253376A1 (zh) * 2020-06-19 2021-12-23 南京正大天晴制药有限公司 一种用于手性药物合成的磷酰胺化合物的制备方法
CN113501853A (zh) * 2021-09-13 2021-10-15 南京颐媛生物医学研究院有限公司 4-硫代尿嘧啶脱氧核苷磷酸酯及其抗病毒药物用途
CN115260263A (zh) * 2022-05-23 2022-11-01 深圳扬厉医药技术有限公司 烷基硫芳基克拉夫定磷酰胺类化合物及其应用
CN115260263B (zh) * 2022-05-23 2025-02-21 浙江扬厉医药技术有限公司 烷基硫芳基克拉夫定磷酰胺类化合物及其应用

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US20190350954A1 (en) 2019-11-21
WO2017223421A1 (en) 2017-12-28
IL263859A (en) 2019-01-31
US20220280542A1 (en) 2022-09-08
EA201990059A1 (ru) 2019-07-31
JP2022116024A (ja) 2022-08-09
ZA201900156B (en) 2019-08-28
US11364257B2 (en) 2022-06-21
SG11201811316YA (en) 2019-01-30
AU2017281531A1 (en) 2019-01-17
PH12018550207A1 (en) 2019-04-15
EP3474863A1 (en) 2019-05-01
IL263859B1 (en) 2023-03-01
JP2019525905A (ja) 2019-09-12
CA3029315A1 (en) 2017-12-28
IL263859B2 (en) 2023-07-01
BR112018076913A2 (pt) 2019-04-02
EP3474863A4 (en) 2020-03-25

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Application publication date: 20190426