WO2009033396A1 - Composés dithiolopyrrolones, leur préparation et leur utilisation - Google Patents

Composés dithiolopyrrolones, leur préparation et leur utilisation Download PDF

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Publication number
WO2009033396A1
WO2009033396A1 PCT/CN2008/072207 CN2008072207W WO2009033396A1 WO 2009033396 A1 WO2009033396 A1 WO 2009033396A1 CN 2008072207 W CN2008072207 W CN 2008072207W WO 2009033396 A1 WO2009033396 A1 WO 2009033396A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
formula
compound
pharmaceutically acceptable
dithiolopyrrolone
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.)
Ceased
Application number
PCT/CN2008/072207
Other languages
English (en)
French (fr)
Chinese (zh)
Inventor
Guoping Wang
Quanhai Liu
Haiyan Sun
Wei Wu
Jian Hou
Lin Yao
Chungang Li
Minyu Liu
Fei Li
Xuejun Wu
Shuai Zhao
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.)
Shanghai Institute of Pharmaceutical Industry
Shanghai Shyndec Pharmaceutical Co Ltd
Original Assignee
Shanghai Institute of Pharmaceutical Industry
Shanghai Modern Pharmaceutical Co Ltd
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 Shanghai Institute of Pharmaceutical Industry, Shanghai Modern Pharmaceutical Co Ltd filed Critical Shanghai Institute of Pharmaceutical Industry
Priority to EP08800719.0A priority Critical patent/EP2192122B1/en
Priority to US12/676,470 priority patent/US8258176B2/en
Priority to JP2010523259A priority patent/JP5186566B2/ja
Publication of WO2009033396A1 publication Critical patent/WO2009033396A1/zh
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A61P37/04—Immunostimulants
    • 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

Definitions

  • the amine reacts to give compound 1-2.
  • compound 1-2 is aminated with a desired amine (e.g., methylamine) at elevated temperature (e.g., 15 CTC) to give compound 1-3.
  • a desired amine e.g., methylamine
  • the compound 1-3 is protected with a trifluoroacetic anhydride to give the compound 1-4.
  • compound 1-4 is deprotected by a mercury salt (such as mercury acetate), dehydrogenated by hydrogen sulfide, and oxidized with an oxidizing agent (such as iodine) to give compound 1-5.
  • the compound 1-5 is hydrolyzed with an acid (e.g., hydrochloric acid) to give a compound of the formula 1-6.
  • the reaction flow chart is as follows:
  • the chloroformate or chloroformamide can be obtained by the following conventional method:
  • the compounds of the present invention can be formulated into pharmaceutical compositions with various conventional pharmaceutical additives such as diluents and excipients.
  • the pharmaceutical composition can be formulated into various types of dosage unit dosage forms, such as tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (solutions and suspensions), etc., depending on the purpose of the treatment. .
  • the administration method of the pharmaceutical composition is not particularly limited.
  • Formulations of various dosage forms can be selected depending on the age, sex and other conditions and symptoms of the patient. For example, tablets, pills, solutions, suspensions, emulsions, granules, and capsules are administered orally; injections can be administered alone or in combination with injectable solutions (eg, glucose solutions and amino acid solutions), if any It is necessary to use a single injection for intramuscular, intradermal, subcutaneous or intraperitoneal injection; suppositories are administered to the rectum.
  • injectable solutions eg, glucose solutions and amino acid solutions
  • mice were subjected to bone marrow smears.
  • the results of microscopic examination showed that the 001, 004, and G-CSF granulosa cell lines proliferated significantly, and the differentiation and maturation accelerated.
  • the granulocyte cell line was severely inhibited after administration in the CTX group, and the blank control group had no specific bone marrow smears.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
PCT/CN2008/072207 2007-09-05 2008-08-29 Composés dithiolopyrrolones, leur préparation et leur utilisation Ceased WO2009033396A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP08800719.0A EP2192122B1 (en) 2007-09-05 2008-08-29 Dithiolopyrrolone compounds, the preparation and the use thereof
US12/676,470 US8258176B2 (en) 2007-09-05 2008-08-29 Dithiolopyrrolone compounds, the preparation and the use thereof
JP2010523259A JP5186566B2 (ja) 2007-09-05 2008-08-29 ジチオロピロロン化合物類、それらの調製及び使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200710045600.X 2007-09-05
CN200710045600XA CN101381371B (zh) 2007-09-05 2007-09-05 二硫杂环戊烯并吡咯酮类化合物及其制备方法和应用

Publications (1)

Publication Number Publication Date
WO2009033396A1 true WO2009033396A1 (fr) 2009-03-19

Family

ID=40451580

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2008/072207 Ceased WO2009033396A1 (fr) 2007-09-05 2008-08-29 Composés dithiolopyrrolones, leur préparation et leur utilisation

Country Status (5)

Country Link
US (1) US8258176B2 (https=)
EP (1) EP2192122B1 (https=)
JP (1) JP5186566B2 (https=)
CN (1) CN101381371B (https=)
WO (1) WO2009033396A1 (https=)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102219724B (zh) * 2010-05-17 2014-10-01 上海现代制药股份有限公司 吡咯酮类化合物及其制备方法和应用
CN106310264B (zh) * 2015-06-29 2019-05-10 上海医药工业研究院 包含二硫杂环戊烯并吡咯酮衍生物的组合物
CN109535174B (zh) * 2018-12-20 2020-06-12 桂林医学院 一种n-芳基二硫吡咯酮-吡喃酮杂合衍生物及其制备方法和应用
CN110981888B (zh) * 2019-11-28 2020-07-28 桂林医学院 N-芳基二硫吡咯酮脲类和氨基酯类衍生物及其制备和应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2170498A (en) 1985-02-04 1986-08-06 Ici Plc Processes for making fungicidal dithiolopyrrolones
JPS63284181A (ja) 1987-05-14 1988-11-21 Nippon Kayaku Co Ltd ジチオロピロ−ル系化合物およびそれを有効成分とする農園芸用殺菌剤
WO1999012543A1 (en) 1997-09-05 1999-03-18 John Malcolm Webster Dithiolopyrrolones and their corresponding monoxides and dioxides as antineoplastic agents
JPH11279179A (ja) 1998-03-25 1999-10-12 Nippon Kayaku Co Ltd ジチオロピロール系化合物およびこれを有効成分とする農園芸用病害虫防除剤
US6020360A (en) 1996-09-18 2000-02-01 Webster; John M. Anticancer property of dithiolopyrrolones
WO2003080624A2 (en) 2002-03-26 2003-10-02 Welichem Biotech Inc. Dithiolopyrrolone derivatives useful in the treatment of proliferative diseases

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4799803B2 (ja) 2000-09-08 2011-10-26 マサチューセッツ インスティテュート オブ テクノロジー Ｇ−ｃｓｆアナログ組成物および方法
CA2663829C (en) * 2006-09-29 2012-02-07 Celestial Pharmaceuticals (Shenzhen) Ltd. Dithiolopyrrolones compounds and their therapeutical applications

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2170498A (en) 1985-02-04 1986-08-06 Ici Plc Processes for making fungicidal dithiolopyrrolones
JPS63284181A (ja) 1987-05-14 1988-11-21 Nippon Kayaku Co Ltd ジチオロピロ−ル系化合物およびそれを有効成分とする農園芸用殺菌剤
US6020360A (en) 1996-09-18 2000-02-01 Webster; John M. Anticancer property of dithiolopyrrolones
WO1999012543A1 (en) 1997-09-05 1999-03-18 John Malcolm Webster Dithiolopyrrolones and their corresponding monoxides and dioxides as antineoplastic agents
JPH11279179A (ja) 1998-03-25 1999-10-12 Nippon Kayaku Co Ltd ジチオロピロール系化合物およびこれを有効成分とする農園芸用病害虫防除剤
WO2003080624A2 (en) 2002-03-26 2003-10-02 Welichem Biotech Inc. Dithiolopyrrolone derivatives useful in the treatment of proliferative diseases
CN1642959A (zh) * 2002-03-26 2005-07-20 维理生物技术公司 具有治疗作用的新型二硫杂环戊烯并吡咯酮类化合物

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HELVETICA CHIMICA ACTA, vol. 85, 2002, pages 4453
See also references of EP2192122A4 *

Also Published As

Publication number Publication date
JP2010538023A (ja) 2010-12-09
US20100210856A1 (en) 2010-08-19
EP2192122A1 (en) 2010-06-02
EP2192122B1 (en) 2014-01-01
US8258176B2 (en) 2012-09-04
EP2192122A4 (en) 2011-05-11
CN101381371B (zh) 2011-05-18
CN101381371A (zh) 2009-03-11
JP5186566B2 (ja) 2013-04-17

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