CN106572989B - 用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂 - Google Patents

用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂 Download PDF

Info

Publication number
CN106572989B
CN106572989B CN201580041767.1A CN201580041767A CN106572989B CN 106572989 B CN106572989 B CN 106572989B CN 201580041767 A CN201580041767 A CN 201580041767A CN 106572989 B CN106572989 B CN 106572989B
Authority
CN
China
Prior art keywords
mds
alkyl
substituted
alkenyl
subject
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
CN201580041767.1A
Other languages
English (en)
Chinese (zh)
Other versions
CN106572989A (zh
Inventor
艾伦·F·利斯特
大卫·A·萨尔曼
约翰·S·科瓦奇
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.)
H Lee Moffitt Cancer Center and Research Institute Inc
Lixte Biotechnology Inc
Original Assignee
H Lee Moffitt Cancer Center and Research Institute Inc
Lixte Biotechnology Inc
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 H Lee Moffitt Cancer Center and Research Institute Inc, Lixte Biotechnology Inc filed Critical H Lee Moffitt Cancer Center and Research Institute Inc
Publication of CN106572989A publication Critical patent/CN106572989A/zh
Application granted granted Critical
Publication of CN106572989B publication Critical patent/CN106572989B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201580041767.1A 2014-07-24 2015-07-23 用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂 Expired - Fee Related CN106572989B (zh)

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

Publications (2)

Publication Number Publication Date
CN106572989A CN106572989A (zh) 2017-04-19
CN106572989B true CN106572989B (zh) 2021-08-27

Family

ID=55163749

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580041767.1A Expired - Fee Related CN106572989B (zh) 2014-07-24 2015-07-23 用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂

Country Status (5)

Country Link
US (3) US10071094B2 (enExample)
EP (1) EP3171870B1 (enExample)
JP (2) JP6453441B2 (enExample)
CN (1) CN106572989B (enExample)
WO (2) WO2016014778A1 (enExample)

Families Citing this family (9)

* 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
US10149847B2 (en) 2012-06-29 2018-12-11 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of diabetes
AU2014251087B2 (en) 2013-04-09 2019-05-02 Lixte Biotechnology, Inc. Formulations of oxabicycloheptanes and oxabicycloheptenes
JP6453441B2 (ja) 2014-07-24 2019-01-16 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
AU2016219853B2 (en) 2015-02-19 2019-05-16 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of depressive and stress disorders
CN113150030A (zh) 2015-05-15 2021-07-23 莱克斯特生物技术公司 氧杂二环庚烷前药
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
DK3551629T3 (da) 2016-12-08 2024-02-12 Lixte Biotechnology Inc Oxabicycloheptaner til modulering af immunrespons
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

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101662939A (zh) * 2007-02-06 2010-03-03 利克斯特生物技术控股公司 氧杂双环庚烷和氧杂双环庚烯，它们的制备及用途

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US8404716B2 (en) 2002-10-15 2013-03-26 Celgene Corporation Methods of treating myelodysplastic syndromes with a combination therapy using lenalidomide and azacitidine
US7879569B2 (en) 2004-11-09 2011-02-01 The Trustees Of The University Of Pennsylvania Methods for diagnosis of myelodysplastic syndromes (MDS)
WO2007092414A2 (en) 2006-02-06 2007-08-16 Lixte Biotechnology Holdings, Inc. Use of phosphatases to treat tumors overexpressing n-cor
US20080267947A1 (en) * 2006-09-07 2008-10-30 Cirrito Thomas P Cancer therapy with cantharidin and cantharidin analogs
EP2185173A4 (en) 2007-08-03 2011-01-12 Lixte Biotechnology Inc USE OF PHOSPHATASES FOR THE TREATMENT OF NEUROBLASTOMES AND MEDULLOGASTOMES
EA018618B1 (ru) 2007-10-01 2013-09-30 Ликсте Байотекнолоджи, Инк. Ингибиторы hdac
WO2010147612A1 (en) 2009-06-18 2010-12-23 Lixte Biotechnology, Inc. Methods of modulating cell regulation by inhibiting p53
WO2010014220A1 (en) 2008-08-01 2010-02-04 Lixte Biotechnology, Inc. Neuroprotective agents for the prevention and treatment of neurodegenerative diseases
CA2730428A1 (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
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
US20150005250A1 (en) * 2011-10-13 2015-01-01 H. Lee Moffitt Cancer Center And Research Institute, Inc. Telomerase reverse transcriptase deficiency as diagnostic marker of myelodysplastic syndrome
US10149847B2 (en) 2012-06-29 2018-12-11 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of diabetes
WO2014005080A1 (en) * 2012-06-29 2014-01-03 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
US20160008336A1 (en) 2013-03-05 2016-01-14 Lixte Biotechnology, Inc. Hdac inhibitors for the treatment of traumatic brain injury
WO2014149494A1 (en) 2013-03-15 2014-09-25 Lixte Biotechnology, Inc. Sanguinarine analog pp2c inhibitors for cancer treatment
AU2014251087B2 (en) 2013-04-09 2019-05-02 Lixte Biotechnology, Inc. Formulations of oxabicycloheptanes and oxabicycloheptenes
JP2016538281A (ja) 2013-11-15 2016-12-08 リクスト・バイオテクノロジー，インコーポレイテッド 血液脳関門を通過するタンパク質ホスファターゼ阻害剤
EP3157336A4 (en) 2014-06-20 2018-01-24 Lixte Biotechnology, Inc. Oxabicycloheptanes and oxabicycloheptenes for the treatment of ovarian cancer
JP6453441B2 (ja) * 2014-07-24 2019-01-16 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
EP3191096A4 (en) 2014-09-12 2018-03-21 Lixte Biotechnology, Inc. Human dosing of phosphatase inhibitor
US9994584B2 (en) 2014-10-15 2018-06-12 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
CN113150030A (zh) 2015-05-15 2021-07-23 莱克斯特生物技术公司 氧杂二环庚烷前药

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101662939A (zh) * 2007-02-06 2010-03-03 利克斯特生物技术控股公司 氧杂双环庚烷和氧杂双环庚烯，它们的制备及用途

Also Published As

Publication number Publication date
CN106572989A (zh) 2017-04-19
US20170340628A1 (en) 2017-11-30
JP2017523178A (ja) 2017-08-17
US10071094B2 (en) 2018-09-11
US20190046525A1 (en) 2019-02-14
WO2016014783A1 (en) 2016-01-28
WO2016014778A1 (en) 2016-01-28
EP3171870A1 (en) 2017-05-31
JP2019069969A (ja) 2019-05-09
EP3171870A4 (en) 2017-12-27
JP6862404B2 (ja) 2021-04-21
US10434100B2 (en) 2019-10-08
EP3171870B1 (en) 2021-10-20
US20170209434A1 (en) 2017-07-27
JP6453441B2 (ja) 2019-01-16

Similar Documents

Publication Publication Date Title
CN106572989B (zh) 用于治疗骨髓增生异常综合征的蛋白磷酸酶2a抑制剂
AU2016213972B2 (en) Combinations of IRS/Stat3 dual modulators and anti-cancer agents for treating cancer
JP2018535244A (ja) 関節疾患及び皮膚疾患の治療のためのラパマイシンとメトホルミンの併用
EP2906564B1 (en) Treating brain cancer using agelastatin a (aa) and analogues thereof
US20220184066A1 (en) Clinical regimen for treating myelodysplastic syndrome with phosphatase inhibitor
KR102382771B1 (ko) 증식성 질환을 위한 조합 치료
CN115605210A (zh) 用于治疗心律失常的烟酰胺单核苷酸和双烟酰胺二核苷酸衍生物
EP2780011B1 (en) Combination therapy for ovarian cancer
CN114867475B (zh) 衣康酸酯及其衍生物/类似物诱导毛发生长的用途
WO2019146130A1 (ja) 胆道がん用抗腫瘍剤および胆道がんの処置方法
BR112020009596A2 (pt) combinações de moduladores duplos de irs/stat3 e anticorpos anti pd-1/pd-l1 para tratar câncer
HK1238548B (en) Protein phosphatase 2a inhibitors for treating myelodysplastic syndromes
AU2008248188A1 (en) Dihydropyridine derivative for treating cancer or a pre-cancerous condition and other conditions
WO2021222350A1 (en) Methods of use for single molecule compounds providing multi-target inhibition to treat covid-19
CN115551518A (zh) 使用n2-喹啉或异喹啉取代的嘌呤衍生物的癌症联合疗法
WO2021146127A1 (en) Use of n2-quincline or isoquinoline substituted purine derivatives in cancer treatment

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for 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: 20210827