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
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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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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
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
AU2014243707B2 (en) * 2013-03-13 2018-08-30 Tufts University Uridine nucleoside derivatives, compositions and methods of use
WO2016172496A1 (en) 2015-04-23 2016-10-27 Constellation Pharmaceuticals, Inc. Lsd1 inhibitors and uses thereof
KR20180030461A (ko) 2015-05-29 2018-03-23 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 연장된 뉴클레오타이드 반복을 포함하는 유전자의 유해 영향 감소를 위한 뉴클레오사이드 제제
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
HUE063848T2 (hu) 2016-10-26 2024-02-28 Constellation Pharmaceuticals Inc LSD1 gátlók és gyógyászati alkalmazásaik
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
US6143279A (en) 1997-08-29 2000-11-07 The University Of North Carolina At Chapel Hill Uridine 5'-diphosphate and analogs useful for treating lung diseases
US8314064B2 (en) * 1998-07-31 2012-11-20 Massachusetts Institute Of Technology Uridine administration stimulates membrane production
US8143234B2 (en) 1998-07-31 2012-03-27 Massachusetts Institute Of Technology Uridine administration improves phosphatide synthesis, synaptic transmission and cognitive function
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
DK2145627T3 (da) 1998-07-31 2014-07-21 Massachusetts Inst Technology Anvendelse af uridin i kombination med cholin til behandling af en humør-lidelse eller en følelsesmæssig lidelse.
US20070004670A1 (en) 1998-07-31 2007-01-04 Richard Wurtman Compositions containing citicoline, and methods of use thereof
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
US7737128B2 (en) 2004-06-10 2010-06-15 The 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
CN101765369A (zh) 2007-03-19 2010-06-30 俄勒冈州由俄勒冈州立大学代表州高等教育委员会行使 曼尼希碱n-氧化物药物
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
WO2012073237A1 (en) 2010-12-01 2012-06-07 Bar-Ilan University Uridine di- or tri-phosphate derivatives and uses thereof
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
AU2014243707B2 (en) 2013-03-13 2018-08-30 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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AU2012315671A1 (en) 2014-04-17
CA2850367C (en) 2021-06-01
US8598141B2 (en) 2013-12-03
IL231787A0 (en) 2014-05-28
JP6162125B2 (ja) 2017-07-12
CN103906745B (zh) 2017-08-25
EP2760858A1 (en) 2014-08-06
JP2014528418A (ja) 2014-10-27
US20190309009A1 (en) 2019-10-10
US20150045319A1 (en) 2015-02-12
IN2014CN03043A (enExample) 2015-07-03
US11072627B2 (en) 2021-07-27
EP2760858B1 (en) 2018-08-08
CN103906745A (zh) 2014-07-02
US8785620B2 (en) 2014-07-22
US20160318968A1 (en) 2016-11-03
AU2012315671B2 (en) 2017-07-20
US20130252919A1 (en) 2013-09-26
CN107353316A (zh) 2017-11-17
US20140066613A1 (en) 2014-03-06
US9227993B2 (en) 2016-01-05
WO2013049686A1 (en) 2013-04-04
CA2850367A1 (en) 2013-04-04
EP2760858A4 (en) 2015-04-22

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