JP4392065B2 - 腫瘍および炎症性疾患治療用の新規プロドラッグ - Google Patents

腫瘍および炎症性疾患治療用の新規プロドラッグ Download PDF

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Publication number
JP4392065B2
JP4392065B2 JP05598397A JP5598397A JP4392065B2 JP 4392065 B2 JP4392065 B2 JP 4392065B2 JP 05598397 A JP05598397 A JP 05598397A JP 5598397 A JP5598397 A JP 5598397A JP 4392065 B2 JP4392065 B2 JP 4392065B2
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compound
amino
alkyl
glycosyl
formula
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Expired - Fee Related
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JP05598397A
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English (en)
Japanese (ja)
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JPH101495A (ja
JPH101495A5 (enExample
Inventor
クラウス・ボスレツト
イエルク・チエツク
マンフレート・ゲルケン
ライナー・シユトラウプ
クロード・モネレ
ジヤン−クロード・フロラン
フレデリツク・シユミツト
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サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング
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Application filed by サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング filed Critical サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
JP05598397A 1996-03-12 1997-03-11 腫瘍および炎症性疾患治療用の新規プロドラッグ Expired - Fee Related JP4392065B2 (ja)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP96103866 1996-03-12
DE96103866:8 1996-03-12

Publications (3)

Publication Number Publication Date
JPH101495A JPH101495A (ja) 1998-01-06
JPH101495A5 JPH101495A5 (enExample) 2005-01-20
JP4392065B2 true JP4392065B2 (ja) 2009-12-24

Family

ID=8222555

Family Applications (1)

Application Number Title Priority Date Filing Date
JP05598397A Expired - Fee Related JP4392065B2 (ja) 1996-03-12 1997-03-11 腫瘍および炎症性疾患治療用の新規プロドラッグ

Country Status (24)

Country Link
US (1) US5935995A (enExample)
EP (1) EP0795334B1 (enExample)
JP (1) JP4392065B2 (enExample)
KR (1) KR100466467B1 (enExample)
CN (1) CN1168733C (enExample)
AT (1) ATE316799T1 (enExample)
AU (1) AU708202B2 (enExample)
BG (1) BG61900B1 (enExample)
BR (1) BRPI9701248B1 (enExample)
CA (1) CA2199664C (enExample)
CZ (1) CZ297994B6 (enExample)
DE (1) DE59712561D1 (enExample)
DK (1) DK0795334T3 (enExample)
ES (1) ES2257756T3 (enExample)
HU (1) HU228764B1 (enExample)
NO (1) NO320322B1 (enExample)
NZ (1) NZ314368A (enExample)
PL (1) PL189604B1 (enExample)
RO (1) RO120951B1 (enExample)
RU (1) RU2191021C2 (enExample)
SG (1) SG50011A1 (enExample)
SI (1) SI0795334T1 (enExample)
TR (1) TR199700178A2 (enExample)
UA (1) UA50719C2 (enExample)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5525606A (en) 1994-08-01 1996-06-11 The United States Of America As Represented By The Department Of Health And Human Services Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines
DE19720312A1 (de) * 1997-05-15 1998-11-19 Hoechst Ag Zubereitung mit erhöhter in vivo Verträglichkeit
CA2328614C (en) * 1999-02-12 2012-06-26 Biostream, Inc. Matrices for drug delivery and methods for making and using the same
US6716452B1 (en) 2000-08-22 2004-04-06 New River Pharmaceuticals Inc. Active agent delivery systems and methods for protecting and administering active agents
IL146284A0 (en) 1999-05-04 2002-07-25 Strakan Ltd Androgen glycosides and pharmaceutical compositions containing the same
US6191119B1 (en) * 1999-10-15 2001-02-20 Supergen, Inc. Combination therapy including 9-nitro-20(S)-camptothecin
US8394813B2 (en) 2000-11-14 2013-03-12 Shire Llc Active agent delivery systems and methods for protecting and administering active agents
DE10058596A1 (de) * 2000-11-25 2002-06-06 Aventis Pharma Gmbh Verfahren zum Screening von chemischen Verbindungen zur Modulierung der Wechselwirkung einer EVH1-Domäne oder eines Proteins mit einer EVH1-Domäne mit einer EVH1-Bindedomäne oder einem Protein mit einer EVH1-Bindedomäne sowie ein Verfahren zum Nachweis besagter Wechselwirkung
US7169752B2 (en) 2003-09-30 2007-01-30 New River Pharmaceuticals Inc. Compounds and compositions for prevention of overdose of oxycodone
US20060014697A1 (en) 2001-08-22 2006-01-19 Travis Mickle Pharmaceutical compositions for prevention of overdose or abuse
US6821998B2 (en) 2001-08-30 2004-11-23 Chemocentryx, Inc. Arylamines as inhibitors of chemokine binding to US28
AU2003244088A1 (en) * 2002-06-20 2004-01-06 Nippon Suisan Kaisha, Ltd. Produrg, medicinal utilization thereof and process for producing the same
US8133881B2 (en) 2003-01-13 2012-03-13 Shire Llc Carbohydrate conjugates to prevent abuse of controlled substances
US7160867B2 (en) * 2003-05-16 2007-01-09 Isotechnika, Inc. Rapamycin carbohydrate derivatives
WO2006038070A2 (en) * 2004-03-30 2006-04-13 Painceptor Pharma Corporation Compositions and methods for modulating gated ion channels
US7825096B2 (en) * 2004-09-08 2010-11-02 The United States Of America As Represented By The Department Of Health And Human Services O6-alkylguanine-DNA alkyltransferase inactivators and beta-glucuronidase cleavable prodrugs
ZA200800314B (en) * 2005-06-29 2009-09-30 Threshold Pharmaceuticals Inc Phosphoramidate alkylator prodrugs
KR20150139620A (ko) * 2007-04-06 2015-12-11 지오팜 온콜로지 인코포레이티드 이소포스포르아미드 머스타드의 염 및 이의 동족체
GB0907551D0 (en) * 2009-05-01 2009-06-10 Univ Dundee Treatment or prophylaxis of proliferative conditions
BR112012004720B1 (pt) * 2009-09-02 2021-06-29 Auckland Uniservices Limited Inibidores de cinase, seus usos, profármaco e composição farmacêutica que o compreende
KR101253399B1 (ko) 2010-10-26 2013-04-11 영남대학교 산학협력단 아포지단백질 ａ－ｉ 및 그 변이체를 포함한 재조합 고밀도지단백질을 이용한 라파마이신 제형
KR101628872B1 (ko) 2014-05-28 2016-06-09 주식회사 레고켐 바이오사이언스 자가-희생 기를 포함하는 화합물
JP7120765B2 (ja) 2015-11-25 2022-08-17 レゴケム バイオサイエンシズ， インク． ペプチド基を含む複合体及びそれに関連する方法
HUE067016T2 (hu) 2015-11-25 2024-09-28 Ligachem Biosciences Inc Önfeláldozó csoportokat tartalmazó konjugátumok és ezekkel kapcsolos eljárások
CN107847605B (zh) 2015-11-25 2021-12-24 乐高化学生物科学股份有限公司 包含分支接头的抗体-药物缀合物及其相关方法
US11229708B2 (en) 2015-12-04 2022-01-25 Seagen Inc. Conjugates of quaternized tubulysin compounds
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
JP7664680B2 (ja) 2017-03-29 2025-04-18 リガケム バイオサイエンシズ， インク． ピロロベンゾジアゼピン二量体前駆体及びそのリガンド－リンカーコンジュゲート化合物
KR20200118827A (ko) 2018-02-02 2020-10-16 마베릭스 온콜로지, 잉크. 젬시타빈 모노포스페이트의 소분자 약물 컨쥬게이트
US11827703B2 (en) 2018-05-09 2023-11-28 Legochem Biosciences, Inc. Compositions and methods related to anti-CD19 antibody drug conjugates
KR20210028544A (ko) 2019-09-04 2021-03-12 주식회사 레고켐 바이오사이언스 인간 ror1에 대한 항체를 포함하는 항체 약물 접합체 및 이의 용도

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3836676A1 (de) * 1988-10-28 1990-05-03 Hoechst Ag Die verwendung von 4h-1-benzopyran-4-on-derivaten, neue 4h-1-benzopyran-4-on-derivate und diese enthaltende arzneimittel
US5284856A (en) * 1988-10-28 1994-02-08 Hoechst Aktiengesellschaft Oncogene-encoded kinases inhibition using 4-H-1-benzopyran-4-one derivatives
CA2025899A1 (en) * 1989-01-23 1990-07-24 Reinhard Bredehorst Site specific in-vivo activation of therapeutic drugs
DE4106389A1 (de) * 1991-02-28 1992-09-03 Behringwerke Ag Fusionsproteine zur prodrug-aktivierung, ihre herstellung und verwendung
AU649421B2 (en) * 1990-05-18 1994-05-26 Sanofi-Aventis Deutschland Gmbh Isoxazole-4-carboxamides and hydroxyalkylidene-cyanoacetamides, drugs containing these compounds and use of such drugs
FR2676058B1 (fr) * 1991-04-30 1994-02-25 Hoechst Lab Prodrogues glycosylees, leur procede de preparation et leur utilisation dans le traitement des cancers.
EP0538799B1 (en) * 1991-10-25 1995-03-15 TUNGSRAM Részvénytársaság Single-capped low-pressure discharge lamp
DE4233152A1 (de) * 1992-10-02 1994-04-07 Behringwerke Ag Antikörper-Enzym-Konjugate zur Prodrug-Aktivierung
CA2081281A1 (en) * 1992-10-23 1994-04-24 Shing-Ming Wang Activation of glucuronide prodrugs by ligand-beta-glucuronidase conjugates for chemotherapy
DE4236237A1 (de) * 1992-10-27 1994-04-28 Behringwerke Ag Prodrugs, ihre Herstellung und Verwendung als Arzneimittel
DE4314556A1 (de) * 1993-05-04 1994-11-10 Behringwerke Ag Modifizierte Antikörperenzymkonjugate und Fusionsproteine sowie ihre Anwendung zur tumorselektiven Therapie
EP0647450A1 (en) * 1993-09-09 1995-04-12 BEHRINGWERKE Aktiengesellschaft Improved prodrugs for enzyme mediated activation
DE4417865A1 (de) * 1994-05-20 1995-11-23 Behringwerke Ag Kombination von Tumornekrose-induzierenden Substanzen mit Substanzen, die durch Nekrosen aktiviert werden, zur selektiven Tumortherapie

Also Published As

Publication number Publication date
MX9701832A (es) 1998-07-31
NZ314368A (en) 1998-10-28
BG101290A (en) 1997-09-30
BRPI9701248B1 (pt) 2022-01-18
US5935995A (en) 1999-08-10
BR9701248A (pt) 1999-10-13
EP0795334A3 (de) 1997-09-24
UA50719C2 (uk) 2002-11-15
NO971116D0 (no) 1997-03-11
AU1620597A (en) 1997-09-18
DE59712561D1 (de) 2006-04-13
HUP9700579A3 (en) 1999-05-28
DK0795334T3 (da) 2006-06-06
RU2191021C2 (ru) 2002-10-20
NO320322B1 (no) 2005-11-21
BG61900B1 (bg) 1998-09-30
JPH101495A (ja) 1998-01-06
HUP9700579A2 (en) 1997-12-29
CN1168733C (zh) 2004-09-29
ATE316799T1 (de) 2006-02-15
ES2257756T3 (es) 2006-08-01
CZ74297A3 (en) 1997-09-17
KR100466467B1 (ko) 2005-06-29
CZ297994B6 (cs) 2007-05-16
TR199700178A2 (tr) 1997-09-21
CN1163895A (zh) 1997-11-05
NO971116L (no) 1997-09-15
SG50011A1 (en) 1998-06-15
HU9700579D0 (en) 1997-04-28
CA2199664A1 (en) 1997-09-12
BR9701248A8 (pt) 2013-06-18
PL318878A1 (en) 1997-09-15
RO120951B1 (ro) 2006-10-30
PL189604B1 (pl) 2005-08-31
EP0795334B1 (de) 2006-02-01
AU708202B2 (en) 1999-07-29
EP0795334A2 (de) 1997-09-17
HU228764B1 (en) 2013-05-28
CA2199664C (en) 2008-05-20
SI0795334T1 (sl) 2006-06-30
KR970065550A (ko) 1997-10-13

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