WO1997044000A3 - Dna-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents - Google Patents

Dna-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents Download PDF

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Publication number
WO1997044000A3
WO1997044000A3 PCT/US1997/009055 US9709055W WO9744000A3 WO 1997044000 A3 WO1997044000 A3 WO 1997044000A3 US 9709055 W US9709055 W US 9709055W WO 9744000 A3 WO9744000 A3 WO 9744000A3
Authority
WO
WIPO (PCT)
Prior art keywords
prodrugs
dna
immunoconjugates
binding
agents
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/US1997/009055
Other languages
French (fr)
Other versions
WO1997044000A2 (en
Inventor
Yuqiang Wang
Susan C Wright
James W Larrick
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.)
Panorama Research Inc
Original Assignee
Panorama Research 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 Panorama Research Inc filed Critical Panorama Research Inc
Priority to AU32170/97A priority Critical patent/AU3217097A/en
Priority to EP97927798A priority patent/EP0918752A4/en
Priority to JP09542898A priority patent/JP2000511893A/en
Publication of WO1997044000A2 publication Critical patent/WO1997044000A2/en
Publication of WO1997044000A3 publication Critical patent/WO1997044000A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • 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
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • 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
    • C07H15/24—Condensed ring systems having three or more rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Cephalosporin Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)

Abstract

The present invention relates to novel DNA alkylating agents and the prodrugs of these agents which are useful as antitumor agents and DNA labelling agents. The compounds are hydroxy dihydrobenzindole oligopeptides and prodrugs thereof wherein the monomeric constituents are derived from monocyclic or bicyclic heterocyclic aromatic residues.
PCT/US1997/009055 1996-05-23 1997-05-22 Dna-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents Ceased WO1997044000A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU32170/97A AU3217097A (en) 1996-05-23 1997-05-22 Dna-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents
EP97927798A EP0918752A4 (en) 1996-05-23 1997-05-22 INDOLE DERIVATIVES FIXING DNA, THEIR PRECURSORS AND IMMUNOCONJUGATES AS ANTI-CANCER AGENTS
JP09542898A JP2000511893A (en) 1996-05-23 1997-05-22 DNA-bound indole derivatives as anticancer agents, prodrugs thereof, and immunoconjugates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/652,883 1996-05-23
US08/652,883 US5843937A (en) 1996-05-23 1996-05-23 DNA-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents

Publications (2)

Publication Number Publication Date
WO1997044000A2 WO1997044000A2 (en) 1997-11-27
WO1997044000A3 true WO1997044000A3 (en) 1997-12-31

Family

ID=24618589

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/009055 Ceased WO1997044000A2 (en) 1996-05-23 1997-05-22 Dna-binding indole derivatives, their prodrugs and immunoconjugates as anticancer agents

Country Status (6)

Country Link
US (1) US5843937A (en)
EP (1) EP0918752A4 (en)
JP (1) JP2000511893A (en)
CN (1) CN1165303C (en)
AU (1) AU3217097A (en)
WO (1) WO1997044000A2 (en)

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US6548530B1 (en) 1995-10-03 2003-04-15 The Scripps Research Institute CBI analogs of CC-1065 and the duocarmycins
JP3649617B2 (en) * 1999-03-26 2005-05-18 独立行政法人科学技術振興機構 Compound capable of cleaving double-stranded DNA and method of use thereof
US6783947B1 (en) * 1999-09-09 2004-08-31 Dade Behring Marburg Gmbh Protecting groups for biological labeling
JP2001136974A (en) * 1999-11-16 2001-05-22 Japan Science & Technology Corp Screening method for bioactive pyrrole-imidazole derivatives
US6559125B1 (en) 2000-01-28 2003-05-06 California Institute Of Technology Polyamide-alkylator conjugates and related products and method
DE50104114D1 (en) * 2000-05-02 2004-11-18 Tietze Lutz F NEW PRODRUGS OF 6-HYDROXY-2,3-DIHYDRO-1H-INDOLEN, 5-HYDROXY-1,2-DIHYDRO-3H-PYRROLO 3,2-E] INDOLEN AND 5-HYDROXY-1,2-DIHYDRO-3H- BENZO E] INDOLES AND 6-HYDROXY-1,2,3,4-TETRAHYDRO-BENZO F] CHINOLINE DERIVATIVES FOR A SELECTIVE CANCER THERAPY
JP4061819B2 (en) * 2000-05-12 2008-03-19 独立行政法人科学技術振興機構 Method for synthesizing interstrand crosslinker
JP5010089B2 (en) * 2000-09-19 2012-08-29 スピロジェン リミテッド Compositions of achiral analogs of CC-1065 and duocarmycin and methods of use thereof
JP4862120B2 (en) * 2001-02-22 2012-01-25 ユニヴァーシティ オブ ブラッドフォード Benz-indole and benzo-quinoline derivatives as prodrugs for tumor therapy
US7626026B2 (en) * 2001-02-22 2009-12-01 University Of Bradford Pyrrolo-indole and pyrrolo-quinoline derivatives as prodrugs for tumour treatment
US7129261B2 (en) * 2001-05-31 2006-10-31 Medarex, Inc. Cytotoxic agents
CA2459308A1 (en) * 2001-09-07 2003-03-20 Dale L. Boger Cbi analogues of cc-1065 and the duocarmycins
JP3898532B2 (en) * 2002-03-08 2007-03-28 独立行政法人科学技術振興機構 New hairpin polyamide
US6756397B2 (en) 2002-04-05 2004-06-29 Immunogen, Inc. Prodrugs of CC-1065 analogs
EP1541579A1 (en) * 2002-06-20 2005-06-15 Nippon Suisan Kaisha, Ltd. Produrg, medicinal utilization thereof and process for producing the same
AU2002330482A1 (en) 2002-09-04 2004-03-29 Perseus Proteomics Inc. Method of diagnosing cancer by detecting gpc3
WO2004035571A1 (en) * 2002-10-15 2004-04-29 Rigel Pharmaceuticals, Inc. Substituted indoles and their use as hcv inhibitors
AU2005221959C1 (en) * 2004-03-13 2010-06-17 Kyoto University Novel indole derivative for alkylating specific base sequence of DNA and alkylating agent and drug each comprising the same
GB0505644D0 (en) 2005-03-18 2005-04-27 Univ London Pharmacy Analogues of the azinomycins as anti-tumour agents and as prodrugs
CA2623236A1 (en) * 2005-09-26 2007-04-05 Medarex, Inc. Human monoclonal antibodies to cd70
JP4248544B2 (en) * 2005-12-19 2009-04-02 株式会社椿本チエイン Movable guide for transmission
EP1994000B1 (en) * 2006-02-02 2017-08-23 Syntarga B.V. Water-soluble cc-1065 analogs and their conjugates
KR20090088946A (en) * 2006-12-14 2009-08-20 메다렉스, 인코포레이티드 Human antibodies binding to CD70 and uses thereof
US9901567B2 (en) 2007-08-01 2018-02-27 Syntarga B.V. Substituted CC-1065 analogs and their conjugates
WO2010008726A1 (en) * 2008-06-16 2010-01-21 Immunogen Inc. Novel synergistic effects
AU2009320481C1 (en) * 2008-11-03 2016-12-08 Syntarga B.V. Novel CC-1065 analogs and their conjugates
AU2011243294C1 (en) 2010-04-21 2015-12-03 Syntarga B.V. Novel conjugates of CC-1065 analogs and bifunctional linkers
AU2015205574B2 (en) 2014-01-10 2019-08-15 Byondis B.V. Method for purifying Cys-linked antibody-drug conjugates
CN105899236B (en) 2014-01-10 2019-07-26 斯索恩生物制药有限公司 Show times carcinomycin ADC of improved internal anti-tumor activity
HUE029672T2 (en) 2014-01-10 2017-03-28 Synthon Biopharmaceuticals Bv Duocarmycin adcs for use in treatment of endometrial cancer
EP3160513B1 (en) 2014-06-30 2020-02-12 Glykos Finland Oy Saccharide derivative of a toxic payload and antibody conjugates thereof
MX2020012718A (en) 2018-05-29 2021-02-16 Intocell Inc Novel benzodiazepine derivatives and uses thereof.
KR20210068591A (en) 2018-10-31 2021-06-09 주식회사 인투셀 Fused heterocyclic benzodiazepine derivatives and uses thereof
US20220213052A1 (en) * 2019-05-01 2022-07-07 The University Of North Carolina At Chapel Hill Inhibitors of rna-binding proteins, compositions thereof, and therapeutic uses therof
WO2023118961A1 (en) * 2021-12-21 2023-06-29 Intocell, Inc. Antibody drug conjugates comprising toxins with polar groups and uses thereof

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US4978757A (en) * 1984-02-21 1990-12-18 The Upjohn Company 1,2,8,8a-tetrahydrocyclopropa (C) pyrrolo [3,2-e)]-indol-4(5H)-ones and related compounds
US5008271A (en) * 1988-10-21 1991-04-16 Kyowa Hakko Kogyo Co., Ltd. DC-88A derivatives
JPH0834789A (en) * 1994-07-26 1996-02-06 Kyorin Pharmaceut Co Ltd Pyrroloindolecarboxylic acid ester derivative and method for producing the same
US5502068A (en) * 1995-01-31 1996-03-26 Synphar Laboratories, Inc. Cyclopropylpyrroloindole-oligopeptide anticancer agents
US6548530B1 (en) * 1995-10-03 2003-04-15 The Scripps Research Institute CBI analogs of CC-1065 and the duocarmycins

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ARISTOFF P A: "CC-1065 ANALOGS: SEQUENCE SPECIFIC DNA-ALKYLATING ANTITUMOR AGENTS", ADVANCES IN MEDICINAL CHEMISTRY, JAI PRESS,, US, vol. 02, 1 January 1993 (1993-01-01), US, pages 67 - 110, XP002907327 *
BOGER D.L., YUN W., HAN N.: "1,2,9,9A-TETRAHYDROCYCLOPROPA¬C¾BENZ¬E¾INDOL-4-ONE (CBI) ANALOGS OFCC-1065 AND THE DUOCARMYCINS: SYNTHESIS AND EVALUATION.", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 03., no. 11., 1 January 1995 (1995-01-01), GB, pages 1429 - 1453., XP000886503, ISSN: 0968-0896, DOI: 10.1016/0968-0896(95)00130-9 *
See also references of EP0918752A4 *

Also Published As

Publication number Publication date
EP0918752A4 (en) 2001-11-21
CN1219841A (en) 1999-06-16
WO1997044000A2 (en) 1997-11-27
EP0918752A2 (en) 1999-06-02
US5843937A (en) 1998-12-01
AU3217097A (en) 1997-12-09
JP2000511893A (en) 2000-09-12
CN1165303C (en) 2004-09-08

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