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WO1996013263A2 - Methodes de traitement de maladies virales par des inhibiteurs de la biosynthese des sphingolipides - Google Patents

Methodes de traitement de maladies virales par des inhibiteurs de la biosynthese des sphingolipides Download PDF

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Publication number
WO1996013263A2
WO1996013263A2 PCT/US1995/014070 US9514070W WO9613263A2 WO 1996013263 A2 WO1996013263 A2 WO 1996013263A2 US 9514070 W US9514070 W US 9514070W WO 9613263 A2 WO9613263 A2 WO 9613263A2
Authority
WO
WIPO (PCT)
Prior art keywords
inhibitor
cycloserine
sphingolipid biosynthesis
hiv
sphingolipid
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/US1995/014070
Other languages
English (en)
Other versions
WO1996013263A3 (fr
Inventor
Meir Lev
K. Soma Sundaram
Yaffa Mizrachi
Arye Rubinstein
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.)
Research Corp Technologies Inc
Original Assignee
Research Corp Technologies 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 Research Corp Technologies Inc filed Critical Research Corp Technologies Inc
Publication of WO1996013263A2 publication Critical patent/WO1996013263A2/fr
Publication of WO1996013263A3 publication Critical patent/WO1996013263A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles

Definitions

  • nucleoside analogs can also inhibit the conversion of normal nucleosides into the nucleoside triphosphate used to synthesize DNA. While inhibition of triphosphate formation can slow the rate of viral replication, inhibition of normal nucleoside triphosphate formation can also have detrimental effects upon the cell. While a number of nucleoside analogs are known to inhibit viral replication, these analogs cause side effects such as anemia, neutropenia, neuropathy, pancreatitis and other problems.
  • the present invention also provides a compartmentalized kit for the treatment or prevention of infection by an enveloped virus which comprises a first compartment adapted to contain an inhibitor of sphingolipid biosynthesis.
  • the present invention provides a method of inhibiting replication of an enveloped virus which comprises contacting a virally-infected cell or a cell susceptible to viral infection with a replication- inhibiting effective amount of at least one inhibitor of sphingolipid biosynthesis.
  • a replication-inhibiting effective amount of an inhibitor of sphingolipid biosynthesis is an amount that is sufficient to detectably reduce viral replication.
  • Viral replication can be assayed as described hereinabove.
  • the inhibitor of sphingolipid biosynthesis is L- cycloserine or a derivative or analog thereof, for example dimeric or acetylated L-cycloserine. In a most preferred embodiment the inhibitor of sphingolipid biosynthesis is L-cycloserine.
  • L-cvcloserine inhibited HIV-1 production.
  • CEM cells were treated with L-cycloserine for 24 hr. prior to infection with HIV-1.
  • L-cycloserine at concentrations from 2.5 to 10 ⁇ g/ml, inhibited HIV production in CEM cells as measured by p24 production in the supernatant (Table III) .
  • L-Cycloserine is non-toxic at levels used to inhibit cerebroside biosynthesis in vivo.
  • mice weighing 8-12 g obtained from Harlan Sprague Dawley, Indianapolis, IN were used at 16 days of age (postweaned) for all experiments.
  • mice Five 16 day old mice per group were injected subcutaneously with L-cycloserine (25 mg/kg body wt) alternate days for 2 months. Controls received saline. The animals were killed, and glucocerebrosides were separated from liver and spleen lipids by borate TLC plates as described in Materials and Methods. Values are means ⁇ SEM of five animals per group. Values for spleen were obtained from pooled samples.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Nouvelle méthode d'inhibition de la réplication des virus axée en particulier sur l'utilisation d'un inhibiteur de la biosynthèse des sphingolipides en vue du traitement ou de la prévention d'infections causées par des virus encapsidés dont le VIH. La cyclosérine L est l'inhibiteur préféré de la biosynthèse des sphingolipides. L'invention porte également sur des compositions pharmaceutiques renfermant des inhibiteurs de la biosynthèse des sphingolipides dont la cyclosérine L.
PCT/US1995/014070 1994-11-01 1995-10-30 Methodes de traitement de maladies virales par des inhibiteurs de la biosynthese des sphingolipides Ceased WO1996013263A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US33296994A 1994-11-01 1994-11-01
US08/332,969 1994-11-01

Publications (2)

Publication Number Publication Date
WO1996013263A2 true WO1996013263A2 (fr) 1996-05-09
WO1996013263A3 WO1996013263A3 (fr) 1996-06-13

Family

ID=23300674

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/014070 Ceased WO1996013263A2 (fr) 1994-11-01 1995-10-30 Methodes de traitement de maladies virales par des inhibiteurs de la biosynthese des sphingolipides

Country Status (1)

Country Link
WO (1) WO1996013263A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000041473A3 (fr) * 1999-01-13 2001-11-29 Jomaa Pharmaka Gmbh Utilisation de 3-isoxazolidinones et d'hydroxylaminoacides pour le traitement d'infections

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5302609A (en) * 1992-12-16 1994-04-12 The Regents Of The University Of Michigan Treatment of diabetic nephropathy

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000041473A3 (fr) * 1999-01-13 2001-11-29 Jomaa Pharmaka Gmbh Utilisation de 3-isoxazolidinones et d'hydroxylaminoacides pour le traitement d'infections

Also Published As

Publication number Publication date
WO1996013263A3 (fr) 1996-06-13

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