IT1164730B - Cytotoxic aglycone glucuronide(s) more active in acid medium - Google Patents

Cytotoxic aglycone glucuronide(s) more active in acid medium

Info

Publication number
IT1164730B
IT1164730B IT50529/79A IT5052979A IT1164730B IT 1164730 B IT1164730 B IT 1164730B IT 50529/79 A IT50529/79 A IT 50529/79A IT 5052979 A IT5052979 A IT 5052979A IT 1164730 B IT1164730 B IT 1164730B
Authority
IT
Italy
Prior art keywords
aglycone
beta
glucuronide
activity
radio
Prior art date
Application number
IT50529/79A
Other languages
Italian (it)
Other versions
IT7950529A0 (en
Inventor
Adolf W Schwimmer
Irwin Steven Schwartz
David Rubin
Original Assignee
Adolf W Schwimmer
Irwin Steven Schwartz
David Rubin
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
Priority claimed from US05/951,269 external-priority patent/US4584368A/en
Priority claimed from US05/951,270 external-priority patent/US4424348A/en
Priority claimed from US06/011,619 external-priority patent/US4327074A/en
Application filed by Adolf W Schwimmer, Irwin Steven Schwartz, David Rubin filed Critical Adolf W Schwimmer
Publication of IT7950529A0 publication Critical patent/IT7950529A0/en
Application granted granted Critical
Publication of IT1164730B publication Critical patent/IT1164730B/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • 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
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • 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
    • 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
    • C07H15/18—Acyclic radicals, substituted by carbocyclic rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2334/00—O-linked chromogens for determinations of hydrolase enzymes, e.g. glycosidases, phosphatases, esterases
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/924—Hydrolases (3) acting on glycosyl compounds (3.2)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Physiology (AREA)
  • Cell Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Biophysics (AREA)
  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Glucuronide having a cytotoxic aglycone which escorts a more active toxic effect in acid medium than in alkaline medium or which is water-soluble in alkaline medium and insoluble or only slightly water-soluble in acid medium. The cpds. is pref. a beta-D-glucronic acid derivative of 2,4-dinitrophenol, m-chlorocresol, 4,6-dinitroocersol, 4-chloro-3,5-zylanol, chlorothymol, 2-phenyl-6-chlorophenyl, 5-chloro-7-iodo-quinoline-8-o-, podophyllotoxin. p-codo-phenol, phenylsuphazole or pref. methacrylonitrile. Used for treating tumours esp. those having a strong beta-glucuronidose activity. The hyper acidification of the tumour cells causes. decongugation of the glucuronide with release of the aglycone at the site of the tumour cells whilst healthy cells are maintained at an alkaline pH. The aglycone may also contain a radio-active isotope to give an in-situ radio-therapeutic effect. These radioactive glucoronide-aglycones can be used to diagnose and pin-point the presence of tumour cells by hyper acidification and use of a radio-isotope e.g. 131I, 133 I or 35S, which emits a ray capable of being detected in a complete body scan. The invention also allows detection of tumours and bacteria having a beta-glucuronidase, activity by detection of the quantity of free glucuronic acid present in the urine. The invention also allows treatment of bacterial injections where the bacteria has strong beta-ducuronidase activity e.g. streptococcus, staphylococcus and E. coli infections.
IT50529/79A 1978-10-13 1979-10-11 Cytotoxic aglycone glucuronide(s) more active in acid medium IT1164730B (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US05/951,269 US4584368A (en) 1978-10-13 1978-10-13 β-Glucuronidase activity and/or pH-dependent pharmaceuticals and thier methods of production
US05/951,270 US4424348A (en) 1978-10-13 1978-10-13 Methods of manufacture of nitrile-containing glucuronic acid conjugates
US06/011,619 US4327074A (en) 1978-10-13 1979-02-12 Method for diagnosis and selective treatment of infections of bacteria having β-glucuronidase activity

Publications (2)

Publication Number Publication Date
IT7950529A0 IT7950529A0 (en) 1979-10-11
IT1164730B true IT1164730B (en) 1987-04-15

Family

ID=27359461

Family Applications (1)

Application Number Title Priority Date Filing Date
IT50529/79A IT1164730B (en) 1978-10-13 1979-10-11 Cytotoxic aglycone glucuronide(s) more active in acid medium

Country Status (12)

Country Link
JP (1) JPS55500837A (en)
AU (1) AU534068B2 (en)
CA (1) CA1148086A (en)
CH (1) CH652724A5 (en)
DE (1) DE2953223T1 (en)
FR (2) FR2440374B1 (en)
GB (1) GB2055044B (en)
IL (1) IL58352A (en)
IT (1) IT1164730B (en)
NL (1) NL7920107A (en)
SE (1) SE461983B (en)
WO (1) WO1980000791A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4490523A (en) * 1981-11-10 1984-12-25 Ely J. Rubin Mandelonitrile triacetyl glucuronate and process for preparing same
AU594855B2 (en) * 1988-01-15 1990-03-15 Baker Norton Pharmaceuticals, Inc. Glucuronic acid derivatives of opioid antagonists
WO1996030003A1 (en) * 1995-03-30 1996-10-03 Werner Kreutz Medicaments for the selective treatment of tumour tissues
WO2014138722A1 (en) * 2013-03-08 2014-09-12 Cognate3 Llc Process for the preparation of a non-corrosive base solution and methods of using same

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB788855A (en) * 1953-06-30 1958-01-08 Ernst Theodore Krebs Improvements in or relating to mandelo-nitrile-glucuronosides and method of making the same
US2985664A (en) * 1957-05-29 1961-05-23 Ernst T Krebs Hexuronic acid derivatives
US3758455A (en) * 1970-05-14 1973-09-11 Chugai Pharmaceutical Co Ltd Reof mycophenolic acid glucuronide and the process for the preparation the
DE2212014A1 (en) * 1971-04-21 1972-10-26 Deutsche Akademie der Wissenschaf ten zu Berlin, χ 1199 Berlin Enzymatic cleavage of chemotherapeutics transport forms - under acid conditions to give tumour-specific chemotherapy
USRE29465E (en) * 1972-08-14 1977-11-01 Eli Lilly And Company Psoriasis treatment with mycophenolic acid
US3880995A (en) * 1973-05-14 1975-04-29 Lilly Co Eli Treatment of arthritis with mycophenolic acid and derivatives
US3959253A (en) * 1973-07-02 1976-05-25 Merck & Co., Inc. β-D-glucosyluronic acid derivatives
DD122386A1 (en) * 1975-06-24 1976-10-05
JPS5325534A (en) * 1976-08-24 1978-03-09 Rikagaku Kenkyusho Mandelic acid glucosides and their anti-cancerous preparations

Also Published As

Publication number Publication date
AU534068B2 (en) 1984-01-05
DE2953223C2 (en) 1989-05-18
FR2440374B1 (en) 1986-03-21
FR2449284A1 (en) 1980-09-12
AU5112079A (en) 1981-04-16
CH652724A5 (en) 1985-11-29
SE461983B (en) 1990-04-23
CA1148086A (en) 1983-06-14
WO1980000791A1 (en) 1980-05-01
SE8004369L (en) 1980-06-12
JPS55500837A (en) 1980-10-23
GB2055044B (en) 1983-04-20
NL7920107A (en) 1980-08-29
IL58352A (en) 1985-11-29
FR2440374A1 (en) 1980-05-30
IT7950529A0 (en) 1979-10-11
DE2953223T1 (en) 1980-11-27
GB2055044A (en) 1981-02-25

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