WO2021223398A1 - Forme cristalline destinée au traitement d'une maladie hépatique et son utilisation - Google Patents

Forme cristalline destinée au traitement d'une maladie hépatique et son utilisation Download PDF

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WO2021223398A1
WO2021223398A1 PCT/CN2020/130060 CN2020130060W WO2021223398A1 WO 2021223398 A1 WO2021223398 A1 WO 2021223398A1 CN 2020130060 W CN2020130060 W CN 2020130060W WO 2021223398 A1 WO2021223398 A1 WO 2021223398A1
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crystal
crystal form
crystals
add
ray powder
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PCT/CN2020/130060
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English (en)
Chinese (zh)
Inventor
高中强
郭维博
何凯敏
田丹
张登科
金伟丽
张海峰
孙江凯
张艳侠
Original Assignee
西安新通药物研究股份有限公司
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Priority claimed from CN202010376833.3A external-priority patent/CN112010905B/zh
Priority claimed from CN202010376938.9A external-priority patent/CN112028940B/zh
Priority claimed from CN202010391424.0A external-priority patent/CN112047990B/zh
Application filed by 西安新通药物研究股份有限公司 filed Critical 西安新通药物研究股份有限公司
Publication of WO2021223398A1 publication Critical patent/WO2021223398A1/fr
Priority to AU2022100062A priority Critical patent/AU2022100062A4/en
Priority to ZA2022/06666A priority patent/ZA202206666B/en

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    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
    • C07C57/13—Dicarboxylic acids
    • C07C57/15—Fumaric acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • 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
    • C07H19/11—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
    • G01N23/20—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
    • G01N23/20—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials
    • G01N23/20008—Constructional details of analysers, e.g. characterised by X-ray source, detector or optical system; Accessories therefor; Preparing specimens therefor
    • G01N23/2005—Preparation of powder samples therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
    • G01N23/20—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials
    • G01N23/207—Diffractometry using detectors, e.g. using a probe in a central position and one or more displaceable detectors in circumferential positions

Definitions

  • the crystal of paradefovir mesylate is selected from one of crystal form A, crystal form B, crystal form C, crystal form D, and crystal form E:
  • the crystal of MB07133 is selected from one of crystal form A, crystal form B, crystal form C, crystal form D, crystal form E, or crystal form F:
  • Figure 1-6 DSC spectrum of tenofovir phosphate a crystal form.
  • Figure 2-5 X-ray powder diffraction pattern of crystal form C paradefovir mesylate.
  • Example 1-21 The stability of tenofovir phosphate type b crystals
  • Example 1-27 Pharmaceutical composition containing tenofovir phosphate type c crystals
  • test parameters are: voltage: 46kv, current: 40mA, copper k ⁇ radiation, ⁇ :
  • This example describes the stability experiment of the crystalline compound of Form B.
  • Example 3-39 The stability of MB07133 crystal form C crystal compound
  • Example 3-40 The stability of MB07133 crystal form D crystal compound
  • Example 3-46 Pharmaceutical composition containing MB07133 crystal form D

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une forme cristalline destinée au traitement d'une maladie hépatique de phosphate de ténofovir (9-[(2R)-2-[(2R,4S)-4-(3-chlorophényl)-2-oxo-1,3,2-dioxaphosphorinane-2-méthoxy]propyl]adénine fumarate), de mésylate de paladovir (mésylate de (+)-cis-9-{2-[4-[(S)-(3-chlorophényl)-2-oxo-1,3,2-dioxaphosphorinane-2-méthylène]-1-éthyl}adénine), de promédicament de cytarabine (4-amino-1-[5-O-(2R,4S)-2-oxy-4-(4-pyridine)-1,3,2-dioxaphosphorinane-2]-β-D-arabinofuranosyl-2(1H)-pyrimidinone ; MB07133), etc. La présente invention concerne également une composition pharmaceutique comprenant la forme cristalline et son utilisation dans la préparation de médicaments.
PCT/CN2020/130060 2020-05-07 2020-11-19 Forme cristalline destinée au traitement d'une maladie hépatique et son utilisation WO2021223398A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2022100062A AU2022100062A4 (en) 2020-05-07 2022-04-27 Crystal form for treating liver disease and use thereof
ZA2022/06666A ZA202206666B (en) 2020-05-07 2022-06-15 Crystal form for treating liver disease and use thereof

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CN202010376938.9 2020-05-07
CN202010376833.3A CN112010905B (zh) 2020-05-07 2020-05-07 甲磺酸帕拉德福韦晶型及其应用
CN202010376833.3 2020-05-07
CN202010376938.9A CN112028940B (zh) 2020-05-07 2020-05-07 替诺福韦磷酸酯晶型及其制备和应用
CN202010391424.0 2020-05-11
CN202010391424.0A CN112047990B (zh) 2020-05-11 2020-05-11 阿糖胞苷前药mb07133晶型及其应用

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1711278A (zh) * 2002-10-31 2005-12-21 美达贝斯制药有限公司 新颖的阿糖胞苷单磷酸盐药物前体
CN1964967A (zh) * 2004-06-08 2007-05-16 症变治疗公司 路易斯酸介导的环状酯的合成
CN101475594A (zh) * 2009-02-06 2009-07-08 廖国超 肝靶向抗病毒前体药物环状磷酸酯及其应用
CN102827206A (zh) * 2012-09-17 2012-12-19 西安新通药物研究有限公司 Pradefovir晶体
CN103333209A (zh) * 2013-07-05 2013-10-02 西安新通药物研究有限公司 替诺福韦前药（hts）新晶体
WO2013167743A1 (fr) * 2012-05-11 2013-11-14 Akron Molecules Gmbh Utilisation de composés pour le traitement de la douleur
CN104710477A (zh) * 2013-12-16 2015-06-17 安徽贝克联合制药有限公司 替诺福韦环膦酸酯化合物及其药学上可接受的盐和其制备方法及应用
CN106659730A (zh) * 2014-07-10 2017-05-10 里普利科股份有限公司 治疗b型肝炎和d型肝炎病毒感染的方法
CN107540710A (zh) * 2016-06-24 2018-01-05 浙江柏拉阿图医药科技有限公司 肝递送抗病毒前体药物核苷环磷酸酯化合物及应用

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1711278A (zh) * 2002-10-31 2005-12-21 美达贝斯制药有限公司 新颖的阿糖胞苷单磷酸盐药物前体
CN1964967A (zh) * 2004-06-08 2007-05-16 症变治疗公司 路易斯酸介导的环状酯的合成
CN101475594A (zh) * 2009-02-06 2009-07-08 廖国超 肝靶向抗病毒前体药物环状磷酸酯及其应用
WO2013167743A1 (fr) * 2012-05-11 2013-11-14 Akron Molecules Gmbh Utilisation de composés pour le traitement de la douleur
CN102827206A (zh) * 2012-09-17 2012-12-19 西安新通药物研究有限公司 Pradefovir晶体
CN103333209A (zh) * 2013-07-05 2013-10-02 西安新通药物研究有限公司 替诺福韦前药（hts）新晶体
CN104710477A (zh) * 2013-12-16 2015-06-17 安徽贝克联合制药有限公司 替诺福韦环膦酸酯化合物及其药学上可接受的盐和其制备方法及应用
CN106659730A (zh) * 2014-07-10 2017-05-10 里普利科股份有限公司 治疗b型肝炎和d型肝炎病毒感染的方法
CN107540710A (zh) * 2016-06-24 2018-01-05 浙江柏拉阿图医药科技有限公司 肝递送抗病毒前体药物核苷环磷酸酯化合物及应用

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