WO1991008775A3 - Derives d'anhydride de l'acide maleique utilises comme agents de conjugaison d'agents anti-tumoraux sur des support desires - Google Patents

Derives d'anhydride de l'acide maleique utilises comme agents de conjugaison d'agents anti-tumoraux sur des support desires Download PDF

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Publication number
WO1991008775A3
WO1991008775A3 PCT/CA1990/000422 CA9000422W WO9108775A3 WO 1991008775 A3 WO1991008775 A3 WO 1991008775A3 CA 9000422 W CA9000422 W CA 9000422W WO 9108775 A3 WO9108775 A3 WO 9108775A3
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WO
WIPO (PCT)
Prior art keywords
hydroxy
nitro
halogen
cyano
lower alkyl
Prior art date
Application number
PCT/CA1990/000422
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English (en)
Other versions
WO1991008775A2 (fr
Inventor
Rene C Gaudreault
Colette Mongrain
Original Assignee
Univ Laval
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 Univ Laval filed Critical Univ Laval
Publication of WO1991008775A2 publication Critical patent/WO1991008775A2/fr
Publication of WO1991008775A3 publication Critical patent/WO1991008775A3/fr

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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
    • C07D487/12—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 three hetero rings
    • C07D487/14—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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

Composés protéiques agissant comme agents de conjugaison d'agents anti-tumoraux, qui correspondent à la formule générale (I), R1 et R2 étant chacun indépendamment des éléments sélectionnés dans le groupe comportant les éléments suivant: atome d'hydrogène, alkyle C1-4, alcoxy C1-4, carboxyalkyle, phényle et phényle substitué par au moins un des composés suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, ou nitro, à condition que R1 et R2 ne soient pas simultanément un atome d'hydrogène et que lorsque R1 ou R2 est un atome d'hydrogène, l'autre ne soit pas -CH2COOH; A étant le résidu d'un agent anti-tumoral contenant au moins un groupe amino disponible pour former une liason amide; et B étant un composé sélectionné dans le groupe composé d'hydroxy; un radical de la formule générale (IIa): -X-R3, X étant O, S ou Se; et R3 étant du phényle; du phényle substitué par au moins un des composés suivants: hydroxy, halogène, alcyle inférieur, alcoxy inférieur, nitro ou cyano; du SO2 alkyle, de l'azobenzène; de l'azobenzène substitué par au moins un des composés suivant: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro ou cyano; de l'isoquinoline; de la pipéridine; du naphtalène; de la pyridine; de la cétopyridine; du benzotriazole substitué par au moins un des composés suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro ou cyano; des imides cycliques contenant 5 à 10 atomes; des imides cycliques contenant 5 à 10 atomes substitués par au moins un des composés suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro, cyano, phényle, phénile substitué par au moins un des composés suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro ou cyano; de la phtalimide; de la phtalimide substituée par au moins un des composés suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro ou cyano; d'alcényle C2-4; d'alcényle C2-4 substitué par au moins un des composants suivants: hydroxy, halogène, alkyle inférieur, alcoxy inférieur, phényle, nitro ou cyano; (a); et un radical de la formule générale (IIb) : -O-NH-CO-R4, R4 étant un alkyle inférieur; un alcoxy inférieur; un phényle; un phényle substitué par au moins un des composants suivants : hydroxy, halogène, alkyle inférieur, alcoxy inférieur, nitro ou cyano; et une lysine ε libre contenant des résidus sélectionnés à partir d'un peptide ou d'une protéine.
PCT/CA1990/000422 1989-11-28 1990-11-28 Derives d'anhydride de l'acide maleique utilises comme agents de conjugaison d'agents anti-tumoraux sur des support desires WO1991008775A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/442,130 US5140013A (en) 1989-11-28 1989-11-28 Maleic anhydride derivatives used as conjugation agents of anti-tumor agents on desired carriers
US442,130 1989-11-28

Publications (2)

Publication Number Publication Date
WO1991008775A2 WO1991008775A2 (fr) 1991-06-27
WO1991008775A3 true WO1991008775A3 (fr) 1991-07-25

Family

ID=23755659

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1990/000422 WO1991008775A2 (fr) 1989-11-28 1990-11-28 Derives d'anhydride de l'acide maleique utilises comme agents de conjugaison d'agents anti-tumoraux sur des support desires

Country Status (3)

Country Link
US (1) US5140013A (fr)
AU (1) AU6754290A (fr)
WO (1) WO1991008775A2 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH04334377A (ja) * 1990-12-31 1992-11-20 Akzo Nv 酸−不安定性リンカー分子
US5415925A (en) * 1992-06-10 1995-05-16 Fiberweb North America, Inc. Gamma structure composite nonwoven fabric comprising at least two nonwoven webs adhesively bonded by a lightweight adhesive web
US6180134B1 (en) * 1993-03-23 2001-01-30 Sequus Pharmaceuticals, Inc. Enhanced ciruclation effector composition and method
US6495348B1 (en) * 1993-10-07 2002-12-17 Regents Of The University Of Minnesota Mitomycin biosynthetic gene cluster
US6524812B1 (en) 1993-10-07 2003-02-25 Regents Of The University Of Minnesota Genes encoding resistance to DNA alkylating agents
US6043098A (en) * 1994-05-17 2000-03-28 Spallholz; Julian E. Method for the preparation of free radical pharmaceuticals, diagnostics and devices using selenium conjugates
US5783454A (en) * 1994-05-17 1998-07-21 Spallholz; Julian E. Method for the preparation of free radical pharmaceuticals using selenium conjugates
DE4433890C2 (de) * 1994-09-22 1999-02-18 Deutsches Krebsforsch Konjugat aus einem Wirkstoff und einem nicht als körperfremd angesehenen, nativen Protein
DE19514087A1 (de) * 1995-04-13 1996-10-17 Deutsches Krebsforsch Konjugat aus einem Wirkstoff, einem Polyether und ggfs. einem nicht als körperfremd angesehenen, nativen Protein
US6030997A (en) * 1998-01-21 2000-02-29 Eilat; Eran Acid labile prodrugs
TWI242000B (en) * 1998-12-10 2005-10-21 Univ Southern California Reversible aqueous pH sensitive lipidizing reagents, compositions and methods of use
US8211468B2 (en) * 1999-06-07 2012-07-03 Arrowhead Madison Inc. Endosomolytic polymers
US6706892B1 (en) 1999-09-07 2004-03-16 Conjuchem, Inc. Pulmonary delivery for bioconjugation
BRPI0003386B8 (pt) * 2000-08-08 2021-05-25 Cristalia Produtos Quim Farmaceuticos Ltda pró-droga homo ou heterodiméricas úteis no tratamento de doenças ou disfunções mediadas por fosfodiesterases; composições farmacêuticas contendo a pró-droga ou seus sais farmacêuticos aceitáveis; processo de obtenção destas pró-drogas
EP1506218B1 (fr) * 2002-05-24 2017-04-12 Arrowhead Pharmaceuticals, Inc. Modification reversible de l'interaction membranaire
US20040151766A1 (en) * 2003-01-30 2004-08-05 Monahan Sean D. Protein and peptide delivery to mammalian cells in vitro
AU2006293023A1 (en) 2005-09-22 2007-03-29 Meiji Seika Kaisha, Ltd. Metallo-beta-lactamase inhibitors
US8618096B2 (en) 2008-07-21 2013-12-31 The Regents Of The University Of California Prodrug compositions and methods for using the same in treating cancer and malaria
EP2720540A4 (fr) 2011-06-17 2015-06-03 Arrowhead Madison Inc Anhydrides maléiques disubstitués ayant une cinétique modifié de fermeture de cycle
JP6889433B2 (ja) 2014-02-14 2021-06-18 ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア 薬剤の選択的送達のためのプロドラッグとしての環状ペルオキシド

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE849610A (fr) * 1976-12-20 1977-04-15 Nouveaux derives du naphtacene, leur preparation et les compositions qui les contenant

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1589539A (en) * 1976-12-20 1981-05-13 Inst Int Pathologie Cellulaire Naphthacene derivatives and their salts
US4631190A (en) * 1981-06-26 1986-12-23 Shen Wei C Acidity-sensitive spacer molecule to control the release of pharmaceuticals from molecular carriers
US4542225A (en) * 1984-08-29 1985-09-17 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
US4764363A (en) * 1986-04-04 1988-08-16 The Procter & Gamble Company Hair styling mousse
US4997913A (en) * 1986-06-30 1991-03-05 Oncogen pH-sensitive immunoconjugates and methods for their use in tumor therapy

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE849610A (fr) * 1976-12-20 1977-04-15 Nouveaux derives du naphtacene, leur preparation et les compositions qui les contenant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Biochemical and Biophysical Research Cimmunications, vol. 102, no. 3, 15 October 1981, Academic Press, Inc., (New York, US), W..C Shen et al.: "Cis-aconityl spacer between daunomycin and macro-molecular carriers: a model of PH-sensitive linkage releasing drug from a lysosomotropic conjugate", pages *

Also Published As

Publication number Publication date
WO1991008775A2 (fr) 1991-06-27
US5140013A (en) 1992-08-18
AU6754290A (en) 1991-07-18

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