WO2005032594A3 - Alkylators linked to polyamides as dna binding agents - Google Patents

Alkylators linked to polyamides as dna binding agents Download PDF

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Publication number
WO2005032594A3
WO2005032594A3 PCT/US2004/032617 US2004032617W WO2005032594A3 WO 2005032594 A3 WO2005032594 A3 WO 2005032594A3 US 2004032617 W US2004032617 W US 2004032617W WO 2005032594 A3 WO2005032594 A3 WO 2005032594A3
Authority
WO
WIPO (PCT)
Prior art keywords
alkylators
polyamides
linked
dna binding
binding agents
Prior art date
Application number
PCT/US2004/032617
Other languages
French (fr)
Other versions
WO2005032594A2 (en
Inventor
Zoltan Szekely
Humcha K Hariprakasha
Christopher J Michejda
Original Assignee
Us Gov Health & Human Serv
Zoltan Szekely
Humcha K Hariprakasha
Christopher J Michejda
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 Us Gov Health & Human Serv, Zoltan Szekely, Humcha K Hariprakasha, Christopher J Michejda filed Critical Us Gov Health & Human Serv
Publication of WO2005032594A2 publication Critical patent/WO2005032594A2/en
Publication of WO2005032594A3 publication Critical patent/WO2005032594A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
    • 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

Abstract

The invention provides an alkylator that is an analog of a compound based on 5-oxo-1a,2,3,5-tetrahydro-1H-3-aza-cyclopropa[c]indene-7-carboxylic acid, 9a-chloromethyl-4-oxo-2,4,9,9a-tetrahydro-1H-2-aza-cyclopropa[1,5]cyclopenta[1,2-a]naphthalene-7-carboxylic acid, or 4-oxo-1,2,4,5,8,8a-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-6-carboxylic acid and conjugates thereof.
PCT/US2004/032617 2003-10-03 2004-10-01 Alkylators linked to polyamides as dna binding agents WO2005032594A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US50854303P 2003-10-03 2003-10-03
US60/508,543 2003-10-03

Publications (2)

Publication Number Publication Date
WO2005032594A2 WO2005032594A2 (en) 2005-04-14
WO2005032594A3 true WO2005032594A3 (en) 2006-02-02

Family

ID=34421756

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/032617 WO2005032594A2 (en) 2003-10-03 2004-10-01 Alkylators linked to polyamides as dna binding agents

Country Status (1)

Country Link
WO (1) WO2005032594A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9901567B2 (en) 2007-08-01 2018-02-27 Syntarga B.V. Substituted CC-1065 analogs and their conjugates
CN106967062A (en) 2008-11-03 2017-07-21 辛塔佳股份有限公司 The analogs of novel C C 1065 and its conjugate
TR201802539T4 (en) 2010-04-21 2018-03-21 Syntarga Bv Conjugates of CC-1065 analogs and bifunctional binders.
IN2014MN02175A (en) * 2012-04-30 2015-08-28 Ucl Business Plc
EP3092010B1 (en) 2014-01-10 2018-07-11 Synthon Biopharmaceuticals B.V. Method for purifying cys-linked antibody-drug conjugates
AU2015205509B2 (en) 2014-01-10 2019-08-15 Byondis B.V. Duocarmycin ADCs showing improved in vivo antitumor activity
CA2935430C (en) 2014-01-10 2018-09-18 Synthon Biopharmaceuticals B.V. Duocarmycin adcs for use in treatment of endometrial cancer

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030894A2 (en) * 2000-09-19 2002-04-18 Taiho Pharmaceutical Co., Ltd. Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins
WO2002095022A2 (en) * 2001-05-21 2002-11-28 Universite De Geneve Sequence-specific dna binding compounds and their use in targeting telomeres and other dna sequences
WO2003072058A2 (en) * 2002-02-27 2003-09-04 The Government Of The United States Of America, Representated By The Secretary, Deparment Of Health And Human Services Dna-binding polyamide drug conjugates

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030894A2 (en) * 2000-09-19 2002-04-18 Taiho Pharmaceutical Co., Ltd. Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins
WO2002095022A2 (en) * 2001-05-21 2002-11-28 Universite De Geneve Sequence-specific dna binding compounds and their use in targeting telomeres and other dna sequences
WO2003072058A2 (en) * 2002-02-27 2003-09-04 The Government Of The United States Of America, Representated By The Secretary, Deparment Of Health And Human Services Dna-binding polyamide drug conjugates

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BARALDI P. G. ET AL: "Design, synthesis, DNA binding and biological evaluation of water soluble hybrid molecules containing two pyrazole analogues of the alkylating cyclopropylpyrroloindole (CPI) subunit of the antitumor agent CC-1065 and polypyrrole minor groove binders", J MED CHEM, vol. 44, 2001, pages 2536 - 2543, XP008049589 *
COZZI P. ET AL: "Recent anticancer cytotoxic agents", CURR MED CHEM-ANTICANCER AGENTS, vol. 4, 2004, pages 93 - 121, XP008049617 *
SONDHI S. M. ET AL: "Lexitropsin conjugates:action on DNA targets", CURRENT MEDICINAL CHEMISTRY, vol. 4, 1997, pages 313 - 358, XP008049616 *
TOTH J. ET AL: "Cytotoxicity and sequence specificity of C-and N-terminus conjugates of N-methylpyrrole polyamides with seco-cyclopropaneindoline", MED CHEM RES, vol. 12, 2003, pages 87 - 93, XP008049619 *
TOTH J. ET AL: "Sequence selective recognition of DNA by hairpin conjugates of a racemic seco-cyclopropaneindoline-2-benzoburancarboxamide and polyamides", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 12, 2002, pages 2245 - 2248, XP008049673 *

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Publication number Publication date
WO2005032594A2 (en) 2005-04-14

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