CN103906745B - 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法 - Google Patents

用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法 Download PDF

Info

Publication number
CN103906745B
CN103906745B CN201280053228.6A CN201280053228A CN103906745B CN 103906745 B CN103906745 B CN 103906745B CN 201280053228 A CN201280053228 A CN 201280053228A CN 103906745 B CN103906745 B CN 103906745B
Authority
CN
China
Prior art keywords
compound
prodrug
salt
pain
compounds
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.)
Expired - Fee Related
Application number
CN201280053228.6A
Other languages
English (en)
Chinese (zh)
Other versions
CN103906745A (zh
Inventor
P·海登
李劲波
董静慧
斯蒂芬·莫斯
拉奎尔·雷维拉-桑切斯
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.)
Tufts University
Original Assignee
Tufts University
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 Tufts University filed Critical Tufts University
Priority to CN201710598982.2A priority Critical patent/CN107353316B/zh
Publication of CN103906745A publication Critical patent/CN103906745A/zh
Application granted granted Critical
Publication of CN103906745B publication Critical patent/CN103906745B/zh
Expired - Fee Related 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
    • C07H19/06—Pyrimidine radicals
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more 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
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • 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
    • C07F9/65742—Esters of oxyacids of phosphorus non-condensed with carbocyclic rings or heterocyclic rings or ring systems
    • 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
    • C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201280053228.6A 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法 Expired - Fee Related CN103906745B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710598982.2A CN107353316B (zh) 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161541919P 2011-09-30 2011-09-30
US61/541,919 2011-09-30
PCT/US2012/058080 WO2013049686A1 (en) 2011-09-30 2012-09-28 Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201710598982.2A Division CN107353316B (zh) 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法

Publications (2)

Publication Number Publication Date
CN103906745A CN103906745A (zh) 2014-07-02
CN103906745B true CN103906745B (zh) 2017-08-25

Family

ID=47996472

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201280053228.6A Expired - Fee Related CN103906745B (zh) 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法
CN201710598982.2A Expired - Fee Related CN107353316B (zh) 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201710598982.2A Expired - Fee Related CN107353316B (zh) 2011-09-30 2012-09-28 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法

Country Status (9)

Country Link
US (6) US8598141B2 (cg-RX-API-DMAC7.html)
EP (1) EP2760858B1 (cg-RX-API-DMAC7.html)
JP (1) JP6162125B2 (cg-RX-API-DMAC7.html)
CN (2) CN103906745B (cg-RX-API-DMAC7.html)
AU (1) AU2012315671B2 (cg-RX-API-DMAC7.html)
CA (1) CA2850367C (cg-RX-API-DMAC7.html)
IL (1) IL231787A (cg-RX-API-DMAC7.html)
IN (1) IN2014CN03043A (cg-RX-API-DMAC7.html)
WO (1) WO2013049686A1 (cg-RX-API-DMAC7.html)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6162125B2 (ja) * 2011-09-30 2017-07-12 タフツ・ユニバーシティ 神経変性障害を処置するためのウリジン二リン酸誘導体、組成物および方法
AU2013323188B2 (en) 2012-09-28 2018-04-19 Tufts University Uridine diphosphate derivatives, prodrugs, compositions and uses thereof
AR095442A1 (es) 2013-03-13 2015-10-14 Univ Tufts Derivados de nucleósido de uridina, composiciones y métodos de uso
CA2904180C (en) * 2013-03-13 2022-05-10 Tufts University Uridine nucleoside derivatives, compositions and methods of use
US10526287B2 (en) 2015-04-23 2020-01-07 Constellation Pharmaceuticals, Inc. LSD1 inhibitors and uses thereof
CA2978521A1 (en) 2015-05-29 2016-12-08 National Yang-Ming University Nucleoside agents for the reduction of the deleterious activity of extended nucleotide repeat containing genes
JP7121731B2 (ja) * 2016-09-26 2022-08-18 タフツ・ユニバーシティ ウリジンヌクレオシド誘導体、組成物及び使用方法
NZ752587A (en) 2016-10-26 2025-09-26 Constellation Pharmaceuticals Inc Lsd1 inhibitors and medical uses thereof
AU2019285303A1 (en) * 2018-06-14 2020-12-17 Katholieke Universiteit Leuven, K.U. Leuven R&D Methods and materials for treating glycosylation disorders
US20230165885A1 (en) * 2020-03-24 2023-06-01 Gliaguard, Inc. Treatment of eye disorders with uridine phosphate derivatives

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101072569A (zh) * 2004-09-15 2007-11-14 麻省理工学院 含有尿苷的组合物及使用其的方法

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0621073B2 (ja) 1986-03-06 1994-03-23 日水製薬株式会社 中枢抑制剤
JP3032053B2 (ja) 1991-09-06 2000-04-10 日水製薬株式会社 ウリジン誘導体及びこれを含有する医薬
US5962459A (en) 1996-05-28 1999-10-05 Polifarma S.P.A. Therapeutic active agent for treatment of neuron degenerative diseases
ID29198A (id) 1997-08-29 2001-08-09 Univ North Carolina Pemakaian uridin 5'-difosfat dan persamaannya untuk mengobati penyakit paru-paru
US8314064B2 (en) * 1998-07-31 2012-11-20 Massachusetts Institute Of Technology Uridine administration stimulates membrane production
US20060069061A1 (en) 1998-07-31 2006-03-30 Dick Wurtman Compositions containing uridine and choline, and methods utilizing same
US8518882B2 (en) 1998-07-31 2013-08-27 Massachusetts Institute Of Technology Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same
US20070004670A1 (en) 1998-07-31 2007-01-04 Richard Wurtman Compositions containing citicoline, and methods of use thereof
US8143234B2 (en) 1998-07-31 2012-03-27 Massachusetts Institute Of Technology Uridine administration improves phosphatide synthesis, synaptic transmission and cognitive function
PT2322187E (pt) 1998-07-31 2014-07-24 Massachusetts Inst Technology Utilização de uridina em combinação com colina para o tratamento de disfunções de memória
GB0004297D0 (en) 2000-02-23 2000-04-12 Ucb Sa 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses
US6875751B2 (en) 2000-06-15 2005-04-05 Idenix Pharmaceuticals, Inc. 3′-prodrugs of 2′-deoxy-β-L-nucleosides
US20050074819A1 (en) * 2003-10-01 2005-04-07 Japan Health Sciences Foundation Screening method of drug for treatment of neuropathic pain
WO2005122767A1 (en) 2004-06-10 2005-12-29 Mclean Hospital Corporation Pyrimidines, such as uridine, in treatments for patients with bipolar disorder
US7851456B2 (en) 2005-06-29 2010-12-14 Inspire Pharmaceuticals, Inc. P2Y6 receptor agonists for treating lung diseases
EP2136626A4 (en) 2007-03-19 2011-02-23 Oregon State Mannich base n-oxide drugs
US7964580B2 (en) 2007-03-30 2011-06-21 Pharmasset, Inc. Nucleoside phosphoramidate prodrugs
WO2010039548A2 (en) 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
CN103339136A (zh) 2010-12-01 2013-10-02 巴伊兰大学 尿苷二-或三-磷酸衍生物以及其用途
JP6162125B2 (ja) 2011-09-30 2017-07-12 タフツ・ユニバーシティ 神経変性障害を処置するためのウリジン二リン酸誘導体、組成物および方法
AU2013323188B2 (en) * 2012-09-28 2018-04-19 Tufts University Uridine diphosphate derivatives, prodrugs, compositions and uses thereof
CA2904180C (en) 2013-03-13 2022-05-10 Tufts University Uridine nucleoside derivatives, compositions and methods of use
AR095442A1 (es) 2013-03-13 2015-10-14 Univ Tufts Derivados de nucleósido de uridina, composiciones y métodos de uso

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101072569A (zh) * 2004-09-15 2007-11-14 麻省理工学院 含有尿苷的组合物及使用其的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
《Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y6 Receptor Agonists:Novel 4-Alkyloxyimino, (S)-Methanocarba, and 50-Triphosphate γ-Ester Modifications》;Hiroshi Maruoka;《J.Med.Chem》;20100506;第53卷;全文 *
《Synthesis and Structure-Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y2, P2Y4, and P2Y6 Receptors》;Ali El-Tayeb;《J.Med.Chem》;20061103;第49卷;7078 *

Also Published As

Publication number Publication date
US20210347807A1 (en) 2021-11-11
WO2013049686A1 (en) 2013-04-04
US20150045319A1 (en) 2015-02-12
US9227993B2 (en) 2016-01-05
CA2850367A1 (en) 2013-04-04
US8598141B2 (en) 2013-12-03
IL231787A0 (en) 2014-05-28
IN2014CN03043A (cg-RX-API-DMAC7.html) 2015-07-03
JP2014528418A (ja) 2014-10-27
US8785620B2 (en) 2014-07-22
CN107353316B (zh) 2020-08-18
IL231787A (en) 2017-05-29
EP2760858B1 (en) 2018-08-08
US20130252919A1 (en) 2013-09-26
US20140066613A1 (en) 2014-03-06
US20190309009A1 (en) 2019-10-10
CN103906745A (zh) 2014-07-02
CA2850367C (en) 2021-06-01
EP2760858A4 (en) 2015-04-22
EP2760858A1 (en) 2014-08-06
US11072627B2 (en) 2021-07-27
US20160318968A1 (en) 2016-11-03
JP6162125B2 (ja) 2017-07-12
AU2012315671A1 (en) 2014-04-17
AU2012315671B2 (en) 2017-07-20
CN107353316A (zh) 2017-11-17

Similar Documents

Publication Publication Date Title
CN103906745B (zh) 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法
JP6913698B2 (ja) ウリジン二リン酸誘導体、プロドラッグ、組成物およびそれらの使用
TWI640533B (zh) 脲嘧啶核苷衍生物、組合物及使用方法
US10138265B2 (en) Uridine nucleoside derivatives, compositions and methods of use
NZ712391B2 (en) Uridine nucleoside derivatives, compositions and methods of use

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20170825