CN107353316B - 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

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CN107353316B
CN107353316B CN201710598982.2A CN201710598982A CN107353316B CN 107353316 B CN107353316 B CN 107353316B CN 201710598982 A CN201710598982 A CN 201710598982A CN 107353316 B CN107353316 B CN 107353316B
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pain
aliphatic
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CN107353316A (zh
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P·海登
李劲波
董静慧
斯蒂芬·莫斯
拉奎尔·雷维拉-桑切斯
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Tufts University
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    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
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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
    • 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
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CN201710598982.2A 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 CN107353316B (zh)

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Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2850367C (en) * 2011-09-30 2021-06-01 Tufts University Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders
US9163055B2 (en) * 2012-09-28 2015-10-20 Tufts University Methods for treating glaucoma using uridine diphosphate derivatives
US10138265B2 (en) 2013-03-13 2018-11-27 Tufts University Uridine nucleoside derivatives, compositions and methods of use
SI2968385T1 (sl) 2013-03-13 2018-10-30 Tufts University Uridin nukleozid derivati, sestavki in metode uporabe
US10526287B2 (en) 2015-04-23 2020-01-07 Constellation Pharmaceuticals, Inc. LSD1 inhibitors and uses thereof
SG11201707513QA (en) 2015-05-29 2017-10-30 Univ Leland Stanford Junior 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
TWI753037B (zh) 2016-10-26 2022-01-21 美商星座製藥公司 Lsd1抑制劑及其用途
EP4190334A1 (en) * 2018-06-14 2023-06-07 Mayo Foundation for Medical Education and Research Methods and materials for treating glycosylation disorders
WO2021194959A1 (en) * 2020-03-24 2021-09-30 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
EP1011688B1 (en) 1997-08-29 2005-02-02 The University of North Carolina at Chapel Hill Use of uridine 5'-diphosphate and analogs thereof for the treatment of lung diseases
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
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
DK1140104T3 (da) 1998-07-31 2008-01-21 Massachusetts Inst Technology Behandling af Alzheimer's sygdom ved forögelse af cytidinniveauer in vivo
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
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
EP1765075A4 (en) 2004-06-10 2010-11-10 Mclean Hospital Corp PYRIMIDINES, AS FORM. uridine; IN THE TREATMENT OF PATIENTS WITH MANIC-DEPRESSIVE PSYCHOSIS
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
AU2009298802A1 (en) 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
US9221868B2 (en) 2010-12-01 2015-12-29 Bar-Ilan University Uridine di- or tri-phosphate derivatives and uses thereof
CA2850367C (en) 2011-09-30 2021-06-01 Tufts University Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders
US9163055B2 (en) 2012-09-28 2015-10-20 Tufts University Methods for treating glaucoma using uridine diphosphate derivatives
SI2968385T1 (sl) * 2013-03-13 2018-10-30 Tufts University Uridin nukleozid derivati, sestavki in metode uporabe
US10138265B2 (en) 2013-03-13 2018-11-27 Tufts University Uridine nucleoside derivatives, compositions and methods of use

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 (3)

* Cited by examiner, † Cited by third party
Title
"Analgesic Effects of Intrathecal Administration of P2Y Nucleotide Receptor Agonists UTP and UDP in Normal and Neuropathic Pain Model Rats";MAIKO OKADA，et al.;《THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》;20021231;第303卷(第1期);66-73 *
"Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y6 Receptor Agonists：Novel 4-Alkyloxyimino, (S)-Methanocarba, and 50-Triphosphate γ-Ester Modifications";Hiroshi Maruoka，et al.;《J. Med. Chem.》;20100506;第53卷;4488-4501 *
"Synthesis and Structure-Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y2, P2Y4, and P2Y6 Receptors";Ali El-Tayeb，et al.;《J. Med. Chem.》;20061103;第49卷;7076-7087 *

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JP2014528418A (ja) 2014-10-27
CA2850367A1 (en) 2013-04-04
EP2760858A4 (en) 2015-04-22
JP6162125B2 (ja) 2017-07-12
US20130252919A1 (en) 2013-09-26
US8598141B2 (en) 2013-12-03
IN2014CN03043A (https=) 2015-07-03
US20150045319A1 (en) 2015-02-12
US8785620B2 (en) 2014-07-22
US20160318968A1 (en) 2016-11-03
AU2012315671B2 (en) 2017-07-20
CN103906745A (zh) 2014-07-02
CN107353316A (zh) 2017-11-17
WO2013049686A1 (en) 2013-04-04
AU2012315671A1 (en) 2014-04-17
IL231787A (en) 2017-05-29
EP2760858B1 (en) 2018-08-08
US11072627B2 (en) 2021-07-27
US20210347807A1 (en) 2021-11-11
US9227993B2 (en) 2016-01-05
US20190309009A1 (en) 2019-10-10
CN103906745B (zh) 2017-08-25
IL231787A0 (en) 2014-05-28
US20140066613A1 (en) 2014-03-06
CA2850367C (en) 2021-06-01

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