JP6453441B2 - 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤 - Google Patents

骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤 Download PDF

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JP6453441B2
JP6453441B2 JP2017504104A JP2017504104A JP6453441B2 JP 6453441 B2 JP6453441 B2 JP 6453441B2 JP 2017504104 A JP2017504104 A JP 2017504104A JP 2017504104 A JP2017504104 A JP 2017504104A JP 6453441 B2 JP6453441 B2 JP 6453441B2
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mds
composition
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lenalidomide
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JP2017523178A (ja
JP2017523178A5 (OSRAM
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リスト、アラン・エフ．
サルマン、デイビッド・エー．
コバッチ、ジョン・エス．
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エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド
エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド
リクスト・バイオテクノロジー，インコーポレイテッド
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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
    • A61K31/33—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics

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  • Health & Medical Sciences (AREA)
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  • Chemical & Material Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
JP2017504104A 2014-07-24 2015-07-23 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤 Expired - Fee Related JP6453441B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201462028729P 2014-07-24 2014-07-24
US62/028,729 2014-07-24
US201462029327P 2014-07-25 2014-07-25
US62/029,327 2014-07-25
PCT/US2015/041714 WO2016014783A1 (en) 2014-07-24 2015-07-23 Protein phosphatase 2a inhibitors for treating myelodysplastic syndromes

Related Child Applications (1)

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JP2018232414A Division JP6862404B2 (ja) 2014-07-24 2018-12-12 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤

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JP2017523178A JP2017523178A (ja) 2017-08-17
JP2017523178A5 JP2017523178A5 (OSRAM) 2018-08-30
JP6453441B2 true JP6453441B2 (ja) 2019-01-16

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JP2017504104A Expired - Fee Related JP6453441B2 (ja) 2014-07-24 2015-07-23 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤
JP2018232414A Expired - Fee Related JP6862404B2 (ja) 2014-07-24 2018-12-12 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤

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US (3) US10071094B2 (OSRAM)
EP (1) EP3171870B1 (OSRAM)
JP (2) JP6453441B2 (OSRAM)
CN (1) CN106572989B (OSRAM)
WO (2) WO2016014783A1 (OSRAM)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019069969A (ja) * 2014-07-24 2019-05-09 エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010147612A1 (en) 2009-06-18 2010-12-23 Lixte Biotechnology, Inc. Methods of modulating cell regulation by inhibiting p53
EP2867239A4 (en) 2012-06-29 2015-12-23 Lixte Biotechnology Inc OXABICYCLOHEPTANES AND OXABICYCLOHEPTENES FOR THE TREATMENT OF DIABETES
WO2014168941A1 (en) 2013-04-09 2014-10-16 Lixte Biotechnology, Inc. Formulations of oxabicycloheptanes and oxabicycloheptenes
AU2016219853B2 (en) 2015-02-19 2019-05-16 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of depressive and stress disorders
MX393461B (es) 2015-05-15 2025-03-24 Lixte Biotechnology Inc Farmacos precursores de oxabicicloheptanos
JP6964593B2 (ja) * 2016-01-27 2021-11-10 リクスト・バイオテクノロジー，インコーポレイテッド ホスファターゼ阻害剤を使用して骨髄異形成症候群を処置するための臨床レジメン
US12168008B2 (en) 2016-12-08 2024-12-17 Lixte Biotechnology, Inc. Oxabicycloheptanes for modulation of immune response
CN113694071B (zh) * 2021-08-31 2025-08-15 上海交通大学医学院附属瑞金医院 清除和/或溶解衰老细胞和/或抑制细胞衰老的化合物用于治疗精神障碍

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8404716B2 (en) 2002-10-15 2013-03-26 Celgene Corporation Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine
US7189740B2 (en) * 2002-10-15 2007-03-13 Celgene Corporation Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes
WO2006052842A2 (en) 2004-11-09 2006-05-18 The Trustees Of The University Of Pennsylvania Methods for diagnosis of myelodysplastic syndromes (mds)
EP1986619A4 (en) 2006-02-06 2010-04-28 Lixte Biotechnology Inc USE OF PHOSPHATASES FOR THE TREATMENT OF TUMORS BY N-COR OVEREXPRESSION
TWI449524B (zh) * 2006-09-07 2014-08-21 Stemline Therapeutics Inc 以斑螫酸酐（ｃａｎｔｈａｒｉｄｉｎ）及斑螫酸酐類似物進行之癌症治療
US7998957B2 (en) 2007-02-06 2011-08-16 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicylcoheptenes, their preparation and use
CA2718472A1 (en) 2007-08-03 2009-02-12 Lixte Biotechnology, Inc. Use of phosphatases to treat neuroblastomas and medulloblastomas
ES2628748T3 (es) 2007-10-01 2017-08-03 Lixte Biotechnology, Inc. Inhibidores de la HDAC
WO2010014220A1 (en) 2008-08-01 2010-02-04 Lixte Biotechnology, Inc. Neuroprotective agents for the prevention and treatment of neurodegenerative diseases
WO2010014141A1 (en) 2008-08-01 2010-02-04 Lixte Biotechnology, Inc. Methods for regulating cell mitosis by inhibiting serine/threonine phosphatase
US8227473B2 (en) 2008-08-01 2012-07-24 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes, their preparation and use
WO2010147612A1 (en) 2009-06-18 2010-12-23 Lixte Biotechnology, Inc. Methods of modulating cell regulation by inhibiting p53
US20120135522A1 (en) 2009-06-18 2012-05-31 Kovach John S Methods of modulating cell regulation by inhibiting p53
WO2011094683A2 (en) 2010-01-29 2011-08-04 H. Lee Moffitt Cancer Center And Research Institute, Inc. Method of identifying myelodysplastic syndromes
US20140235649A1 (en) 2011-05-24 2014-08-21 Lixte Biotechnology, Inc. Use of phosphatase inhibitors or histone deacetylase inhibitors to treat diseases characterized by loss of protein function
WO2013056211A2 (en) * 2011-10-13 2013-04-18 H. Lee Moffitt Cancer Center & Research Institute, Inc. Telomerase reverse transcriptase deficience as diagnostic marker of myelodysplastic syndrome
EP2867239A4 (en) 2012-06-29 2015-12-23 Lixte Biotechnology Inc OXABICYCLOHEPTANES AND OXABICYCLOHEPTENES FOR THE TREATMENT OF DIABETES
EP2870161B1 (en) 2012-06-29 2018-08-08 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of reperfusion injury
US9738933B2 (en) * 2012-12-05 2017-08-22 H. Lee Moffitt Cancer Center And Research Institute, Inc. RNF41 as a biomarker predicting response to lenalidomide in non-del(5q) MDS
EP2964026A4 (en) 2013-03-05 2016-08-17 Lixte Biotechnology Inc HDAC INHIBITORS FOR THE TREATMENT OF TRAUMATIC BRAIN INJURY
US20160009727A1 (en) 2013-03-15 2016-01-14 Lixte Biotechnology, Inc. Sanguinarine analog pp2c inhibitors for cancer treatment
WO2014168941A1 (en) 2013-04-09 2014-10-16 Lixte Biotechnology, Inc. Formulations of oxabicycloheptanes and oxabicycloheptenes
WO2015073802A1 (en) 2013-11-15 2015-05-21 Lixte Biotechnology, Inc. Protein phosphatase inhibitors that cross the blood brain barrier
US20170136008A1 (en) 2014-06-20 2017-05-18 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of ovarian cancer
US10071094B2 (en) * 2014-07-24 2018-09-11 H. Lee Moffitt Cancer Center And Research Institute, Inc. Protein phosphatase 2A inhibitors for treating myelodysplastic syndromes
CN107072991A (zh) 2014-09-12 2017-08-18 莱克斯特生物技术公司 磷酸酶抑制剂的人类给药
WO2016061193A1 (en) 2014-10-15 2016-04-21 Lixte Biotechnology, Inc. Process of synthesizing 3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo[2.2.1] heptane-2-carboxylic acid
AU2016219853B2 (en) 2015-02-19 2019-05-16 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of depressive and stress disorders
MX393461B (es) 2015-05-15 2025-03-24 Lixte Biotechnology Inc Farmacos precursores de oxabicicloheptanos

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019069969A (ja) * 2014-07-24 2019-05-09 エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド 骨髄異形成症候群を治療するためのタンパク質ホスファターゼ２ａ阻害剤

Also Published As

Publication number Publication date
EP3171870A4 (en) 2017-12-27
WO2016014783A1 (en) 2016-01-28
US20190046525A1 (en) 2019-02-14
US20170209434A1 (en) 2017-07-27
JP2017523178A (ja) 2017-08-17
JP2019069969A (ja) 2019-05-09
US10434100B2 (en) 2019-10-08
US10071094B2 (en) 2018-09-11
EP3171870B1 (en) 2021-10-20
EP3171870A1 (en) 2017-05-31
WO2016014778A1 (en) 2016-01-28
CN106572989B (zh) 2021-08-27
CN106572989A (zh) 2017-04-19
US20170340628A1 (en) 2017-11-30
JP6862404B2 (ja) 2021-04-21

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