WO2008050600A1 - Agent thérapeutique ou préventif pour des maladies réfractaires, basé sur la mort cellulaire induite par le stress oxydatif en tant que contexte moléculaire - Google Patents

Agent thérapeutique ou préventif pour des maladies réfractaires, basé sur la mort cellulaire induite par le stress oxydatif en tant que contexte moléculaire Download PDF

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Publication number
WO2008050600A1
WO2008050600A1 PCT/JP2007/069619 JP2007069619W WO2008050600A1 WO 2008050600 A1 WO2008050600 A1 WO 2008050600A1 JP 2007069619 W JP2007069619 W JP 2007069619W WO 2008050600 A1 WO2008050600 A1 WO 2008050600A1
Authority
WO
WIPO (PCT)
Prior art keywords
therapeutic
cell death
group
oxidative stress
compound
Prior art date
Application number
PCT/JP2007/069619
Other languages
English (en)
Japanese (ja)
Inventor
Kazunori Tanaka
Joh-E Ikeda
Noriaki Hirayama
Takuya Kanno
Original Assignee
Neugen Pharma 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 Neugen Pharma Inc. filed Critical Neugen Pharma Inc.
Priority to JP2008540936A priority Critical patent/JPWO2008050600A1/ja
Publication of WO2008050600A1 publication Critical patent/WO2008050600A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/18—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Definitions

  • the present invention relates to a therapeutic or prophylactic agent for intractable diseases whose molecular background is oxidative stress cell death.
  • the C1-C3 alkyl group of the C6-C10 aryl group that may have a C1-C3 alkyl group as a substituent in R 2 is preferably a methyl group.
  • the aryl group is preferably a phenyl group.
  • the C6_C10 aryl group having a C1-C3 alkyl group as a substituent for R 2 is more preferably a 2,4,6-trimethylphenyl group.
  • the compound according to the third aspect of the present invention is a compound represented by the following general formula (3).
  • the compounds represented by the formulas (1), (2), (3), (4A) to (9A), and pharmaceutically acceptable salts thereof used in the present invention include the compounds listed above. All stereoisomers (eg, enantiomers, diastereomers (including cis and trans geometric isomers)), Semi-, and other mixtures are included.
  • Hydroxypropylmethylcellulose shellac, talc, carnauba wax, paraffin, etc.
  • ALS Amyotrophic lateral sclerosis
  • SH-SY5Y cells were seeded in a 96-well microplate (BD Falcon, PRIMARIA, Catalog # 353872) at a cell density of l.OxlO 4 cells / well, cultured for 24 hours, and then 10 M all-trans-retinoic acid (Wako) Differentiation was induced by culturing in the aforementioned medium containing 5 days.
  • Differentiation-induced SH—SY5Y Itoda Tsuki-Bag compound with final concentration of 5 ⁇ ⁇ , 1 ⁇ , 5 ⁇ ⁇ , 10 ⁇ ⁇ , 20 ⁇ ⁇ , 30 ⁇ ⁇ , 40 ⁇ ⁇ , 50 ⁇ ⁇ 1 ⁇ was added and further cultured for 24 hours.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Psychology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un agent thérapeutique ou préventif destiné à une maladie réfractaire, basé sur la mort cellulaire induite par le stress oxydatif en tant que contexte moléculaire. Selon l'invention, ledit agent contient un composé représenté par la formule générale suivante (1) ou par un sel pharmaceutiquement acceptable de celui-ci en tant qu'ingrédient actif. (1) Ladite formule se décompose de la manière suivante : R1 représente un atome d'hydrogène, et R2 représente un groupe aryle en C6-C10 qui peut avoir un groupe alkyle en C1-C3 en tant que substituant ; ou R1 et R2 peuvent être combinés l'un avec l'autre pour former un cycle tétrahydrofuranyle avec l'atome d'oxygène adjacent ; et R3 et R4 sont indépendants l'un de l'autre et représentent un atome d'hydrogène, un groupe pyridyle ou un groupe aryle en C6-C10 alkyle en C1-C3 qui peut présenter un atome d'halogène en tant que substituant.
PCT/JP2007/069619 2006-10-25 2007-10-05 Agent thérapeutique ou préventif pour des maladies réfractaires, basé sur la mort cellulaire induite par le stress oxydatif en tant que contexte moléculaire WO2008050600A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2008540936A JPWO2008050600A1 (ja) 2006-10-25 2007-10-05 酸化ストレス性細胞死を分子背景とする難治性疾患の治療または予防剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006-290084 2006-10-25
JP2006290084 2006-10-25

Publications (1)

Publication Number Publication Date
WO2008050600A1 true WO2008050600A1 (fr) 2008-05-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2007/069619 WO2008050600A1 (fr) 2006-10-25 2007-10-05 Agent thérapeutique ou préventif pour des maladies réfractaires, basé sur la mort cellulaire induite par le stress oxydatif en tant que contexte moléculaire

Country Status (2)

Country Link
JP (1) JPWO2008050600A1 (fr)
WO (1) WO2008050600A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012014699A1 (fr) 2010-07-28 2012-02-02 湧永製薬株式会社 Agent thérapeutique pour des maladies neurologiques

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10287634A (ja) * 1997-04-11 1998-10-27 Otsuka Pharmaceut Co Ltd ベンゼン誘導体
JP2002518380A (ja) * 1998-06-18 2002-06-25 ブリストル−マイヤーズ スクイブ カンパニー サイクリン依存キナーゼの炭素置換アミノチアゾール抑制剤
US20030199523A1 (en) * 2002-02-28 2003-10-23 Snutch Terrance P. Heterocyclic calcium in channel blockers
JP2004501863A (ja) * 2000-01-19 2004-01-22 アルテオン　インコーポレーテッド チアゾール、イミダゾールおよびオキサゾール化合物、ならびにタンパク質老化関連疾患の治療
WO2005026137A2 (fr) * 2003-09-06 2005-03-24 Vertex Pharmaceuticals Incorporated Modulateurs de transporteurs a cassette de liaison a l'atp
JP2005518391A (ja) * 2001-12-21 2005-06-23 ノボ　ノルディスク　アクティーゼルスカブ Ｇｋ活性化剤としてのアミド誘導体
JP2006514684A (ja) * 2002-10-30 2006-05-11 バーテックス　ファーマシューティカルズ　インコーポレイテッド Ｒｏｃｋおよび他のプロテインキナーゼとして有用な組成物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10287634A (ja) * 1997-04-11 1998-10-27 Otsuka Pharmaceut Co Ltd ベンゼン誘導体
JP2002518380A (ja) * 1998-06-18 2002-06-25 ブリストル−マイヤーズ スクイブ カンパニー サイクリン依存キナーゼの炭素置換アミノチアゾール抑制剤
JP2004501863A (ja) * 2000-01-19 2004-01-22 アルテオン　インコーポレーテッド チアゾール、イミダゾールおよびオキサゾール化合物、ならびにタンパク質老化関連疾患の治療
JP2005518391A (ja) * 2001-12-21 2005-06-23 ノボ　ノルディスク　アクティーゼルスカブ Ｇｋ活性化剤としてのアミド誘導体
US20030199523A1 (en) * 2002-02-28 2003-10-23 Snutch Terrance P. Heterocyclic calcium in channel blockers
JP2006514684A (ja) * 2002-10-30 2006-05-11 バーテックス　ファーマシューティカルズ　インコーポレイテッド Ｒｏｃｋおよび他のプロテインキナーゼとして有用な組成物
WO2005026137A2 (fr) * 2003-09-06 2005-03-24 Vertex Pharmaceuticals Incorporated Modulateurs de transporteurs a cassette de liaison a l'atp

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE REGISTRY [online] accession no. STN Database accession no. (752219-52-6) *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012014699A1 (fr) 2010-07-28 2012-02-02 湧永製薬株式会社 Agent thérapeutique pour des maladies neurologiques
US8975411B2 (en) 2010-07-28 2015-03-10 Neugen Pharma Inc. Therapeutic agent for neurological diseases
TWI482765B (zh) * 2010-07-28 2015-05-01 Neugen Pharma Inc Treatment of neurological diseases
JP5782032B2 (ja) * 2010-07-28 2015-09-24 株式会社ニュージェン・ファーマ 神経疾患治療薬

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