WO1990003172A2 - Bile acids for treatment of viral infections - Google Patents

Bile acids for treatment of viral infections Download PDF

Info

Publication number
WO1990003172A2
WO1990003172A2 PCT/GB1989/001080 GB8901080W WO9003172A2 WO 1990003172 A2 WO1990003172 A2 WO 1990003172A2 GB 8901080 W GB8901080 W GB 8901080W WO 9003172 A2 WO9003172 A2 WO 9003172A2
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
represent
treatment
disease
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/GB1989/001080
Other languages
French (fr)
Other versions
WO1990003172A3 (en
Inventor
Christopher James Sharpe
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.)
Fisons Ltd
Original Assignee
Fisons Ltd
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 GB888822012A external-priority patent/GB8822012D0/en
Priority claimed from GB888822015A external-priority patent/GB8822015D0/en
Priority claimed from GB888822020A external-priority patent/GB8822020D0/en
Application filed by Fisons Ltd filed Critical Fisons Ltd
Priority to KR1019900701043A priority Critical patent/KR900701278A/en
Publication of WO1990003172A2 publication Critical patent/WO1990003172A2/en
Publication of WO1990003172A3 publication Critical patent/WO1990003172A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • This invention relates to a new use of certain known compounds in the treatment of viral infections caused by enveloped viruses, and to pharmaceutical compositions containing them.
  • bile acids Naturally occuring bile acids are produced by the liver, and certain of these have been used in the treatment of gallstones for a number of years. More recently, European Patent Application 0285285 disclosed the use of bile acids in the treatment of viral infections.
  • R 1 and R 2 both represent (H, ⁇ -OH) or both represent O;
  • R 3 represents (H,H) or 0; and R 4 represents OH or NH(CH 2 ) 2 S0 3 H; and pharmaceutically acceptable salts thereof; provided that , i) when R 1 and R 2 both represent (H, ⁇ -OH) and R 3 represents (H,H) , then R 4 represents NH(CH 2 ) 2 S0 3 H; and ii) when R 1 and R 2 both represent 0 and R 3 represents 0, then R 4 represents NH(CH 2 ) 2 S0 3 H; for use as a pharmaceutical.
  • the compounds which we provide as pharmaceuticals are also known as 3,7-diketocholanic acid [R 1 and R 2 both represent O, R 3 represents (H,H) and R 4 represents OH]; tauro-3,7-diketocholanic acid [R 1 and R 2 both represent O, R 3 represents (H,H) and R 4 represents NH(CH 2 ) 2 S0 3 H] ; taurodehydrocholic acid [R 1 and R 2 both represent 0, R 3 represents 0 and R 4 represents NH(CH 2 ) 2 S0 3 H] ; taurochenodeoxycholic acid [R 1 and R 2 both represent (H, ⁇ -0H), R 3 represents (H,H) and R 4 represents NH(CH 2 ) S0 3 H] ; 3 ⁇ ,7 ⁇ -dihydroxy-12-ketocholanic acid [R 1 and R 2 both represent (H, -0H) , R 3 represents 0 and R 4 represents OH] ; and tauro-3 ⁇ .,7 ⁇ -dihydroxy
  • dehydrocholic acid [R 1 and R 2 both represent O, R 3 represents O and R 4 represents OH] .
  • Tauro derivatives may be obtained from the parent bile acid by a mixed anhydride synthesis, eg using ethyl chloroformate and taurine.
  • bile acids are usually ionised and the terms 'bile acid 1 and "bile salt 1 are used interchangeably.
  • Pharmaceutically acceptable salts of the compounds which may be mentioned include certain alkali metal salts, particularly the sodium salts, and certain alkaline earth metal salts, particularly the calcium salts.
  • enveloped virus we mean a virus having a lipid outer coat. Included in this definition are the human immunodeficiency, influenza, parainfluenza and herpes viruses. Thus, diseases of particular interest are AIDS, influenza, parainfluenza and herpes.
  • the compound of formula I may be administered to a patient by any convenient means which results in their introduction into the systemic circulation.
  • they may be introduced parenterally eg by injection (intravenously, intramuscularly or subcutaneously) , topically, orally, using plasmaphoresis, or by inhalation in the form of a non-pressurised powder or an aerosol formulation.
  • the invention further provides a pharmaceutical composition
  • a pharmaceutical composition comprising as active ingredient at least one compound of formula I as defined above (preferably less than 80%, and more preferably less than 50% by weight) in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
  • Suitable adjuvants, diluents or carriers are: for tablets, capsules and dragees - microcrystalline cellulose, calcium phosphate, diatomaceous earth, a sugar such as lactose, dextrose or mannitol, talc, stearic acid, starch, sodium bicarbonate and/or gelatin; for suppositories - natural or hardened oils or waxes; and for inhalation compositions - coarse lactose.
  • the compound of formula I is preferably in a form having a mass median diameter of from 0.01 to 10 microns.
  • the compositions may also contain suitable preserving, stabilising and wetting agents, solubilisers, sweetening and colouring agents and flavourings.
  • the compositions may, if desired, be formulated in sustained release form.
  • the dosage administered will vary with the compound employed, the mode of administration and the disease indicated. However, in general, satisfactory results are obtained when the compounds are administered at a dosage which produces a concentration in the blood stream of from l-100 ⁇ g/ml, preferably 5-100 ⁇ g/ml.
  • unit dosage forms suitable for administration comprise from lmg to 2500mg, and preferably 2mg to 2000mg of the compound preferably admixed with a solid or liquid pharmaceutically acceptable diluent, carrier or adjuvant.
  • a method of treatment or prophylaxis of a disease caused by an enveloped virus which comprises administration of a therapeutically effective amount of a compound of formula I as defined above to a patient suffering from or at risk of contracting such a disease.
  • the compounds of formula I have the advantage that they are less toxic, more efficacious, are longer acting, have a broader range of activity, are more potent, produce fewer side effects, are more easily absorbed or have other useful pharmacological properties, than compounds previously used against the diseases mentioned above.
  • Test A The antiviral activity of the compounds of formula I which may be used in the present invention were tested in the procedures set out in Tests A and B below. Test A
  • Mammalian lymphocyte (H9IIIB) cells which were chronically infected with HIV were diluted to a concentration of 2xl0 5 ml "1 in a culture medium (RPMI 1640 - which is a mixture of amino acids, salts, glucose and vitamins available from Gibco) .
  • a culture medium RPMI 1640 - which is a mixture of amino acids, salts, glucose and vitamins available from Gibco.
  • 0.5ml aliguots of this solution were placed in the wells of a tissue culture plate together with 0.5ml aliguots of an aqueous solution of "the compound under test.
  • a range of initial concentrations of test compound solution were used (0.4, 4, 40 and 400mgml _1 ) , thus giving final test compound concentrations of 0.1, 1, 10 and lOOmgml -1 in the wells.
  • Uninfected human lymphocyte (8166) cells (1ml of a lxl0 6 ml _1 solution in
  • the infected cell/test compound mixtures were then incubated at 37 ⁇ C. On following days, for example day 1 and day 4, 200 ⁇ l samples of the supernatant liquor from each well were removed and tested for antigen P24, which is produced by the human immunodeficiency virus using the standard Coulter Antigen (P24) ELISA test. The presence of antigen P24 thus indicates the presence of HIV.
  • Test B The test described above gives an indication both of the test compound's inhibitory effect on virus release, and of the test compound's inhibitory effect on virus attachment and penetration.
  • H9IIIB Mammalian lymphocyte (H9IIIB) cells which were chronically infected with HIV were diluted to a concentration of 2xl0 5 ml ⁇ 1 in a culture medium (RPMI).
  • test compound concentrations 0.1, 1, 10 and lOOmgml "1 in the wells.
  • the infected cell/test compound mixtures were then incubated at 37 ⁇ C. On following days, for example day 1 and day 4, 200 ⁇ l samples of the supernatant liquor from each well were removed and tested for antigen P24, which is produced by the human immunodeficiency virus. The presence of antigen P24 thus indicates the presence of HIV.
  • the test described above gives an indication of the test compound's inhibitory effect on virus release.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compounds of formula (I), wherein R?1 and R2¿ both represent (H, α-OH) or both represent O; R3 represents (H, H) or O; and R4 represents OH or NH(CH¿2?)2SO3H; and pharmaceutically acceptable salts thereof; provided that when R?1 and R2¿ both represent (H, α-OH) and R3 represents (H, H), then R4 represents NH(CH¿2?)2SO3H; are useful as pharmaceuticals, in particular in the treatment of diseases caused by enveloped viruses.

Description

This invention relates to a new use of certain known compounds in the treatment of viral infections caused by enveloped viruses, and to pharmaceutical compositions containing them.
Naturally occuring bile acids are produced by the liver, and certain of these have been used in the treatment of gallstones for a number of years. More recently, European Patent Application 0285285 disclosed the use of bile acids in the treatment of viral infections.
We have now surprisingly found a small group of bile acids and pharmaceutically acceptable salts thereof which are particularly useful in the treatment of diseases caused by enveloped viruses.
Thus, according to the present invention, there is provided a compound of formula I,
rf
Figure imgf000003_0001
wherein
R1 and R2 both represent (H,α-OH) or both represent O;
R3 represents (H,H) or 0; and R4 represents OH or NH(CH2)2S03H; and pharmaceutically acceptable salts thereof; provided that , i) when R1 and R2 both represent (H,α-OH) and R3 represents (H,H) , then R4 represents NH(CH2)2S03H; and ii) when R1 and R2 both represent 0 and R3 represents 0, then R4 represents NH(CH2)2S03H; for use as a pharmaceutical.
We further provide the use of a compound of formula I as defined above but without proviso (ii) , as active ingredient in the manufacture of a medicament for the treatment or prophylaxis of diseases caused by enveloped viruses.
The compounds which we provide as pharmaceuticals are also known as 3,7-diketocholanic acid [R1 and R2 both represent O, R3 represents (H,H) and R4 represents OH]; tauro-3,7-diketocholanic acid [R1 and R2 both represent O, R3 represents (H,H) and R4 represents NH(CH2)2S03H] ; taurodehydrocholic acid [R1 and R2 both represent 0, R3 represents 0 and R4 represents NH(CH2)2S03H] ; taurochenodeoxycholic acid [R1 and R2 both represent (H,α-0H), R3 represents (H,H) and R4 represents NH(CH2) S03H] ; 3α,7α-dihydroxy-12-ketocholanic acid [R1 and R2 both represent (H, -0H) , R3 represents 0 and R4 represents OH] ; and tauro-3α.,7α-dihydroxy-12-ketocholanic acid [R1 and R2 both represent (H,α-0H), R3 represents 0 and R4 represents NH(CH2)2S03H] .
The compound which we provide for use in the manufacture of a medicament for the treatment or prophylaxis of diseases caused by enveloped viruses in addition to those named above is known as dehydrocholic acid [R1 and R2 both represent O, R3 represents O and R4 represents OH] .
Tauro derivatives may be obtained from the parent bile acid by a mixed anhydride synthesis, eg using ethyl chloroformate and taurine.
At physiological pH, bile acids are usually ionised and the terms 'bile acid1 and "bile salt1 are used interchangeably. Pharmaceutically acceptable salts of the compounds which may be mentioned include certain alkali metal salts, particularly the sodium salts, and certain alkaline earth metal salts, particularly the calcium salts.
By "enveloped virus" we mean a virus having a lipid outer coat. Included in this definition are the human immunodeficiency, influenza, parainfluenza and herpes viruses. Thus, diseases of particular interest are AIDS, influenza, parainfluenza and herpes.
We prefer the compound of formula I as defined above to be dehydrocholic acid or taurochenodeoxycholic acid. The compound of formula I may be administered to a patient by any convenient means which results in their introduction into the systemic circulation. Thus they may be introduced parenterally eg by injection (intravenously, intramuscularly or subcutaneously) , topically, orally, using plasmaphoresis, or by inhalation in the form of a non-pressurised powder or an aerosol formulation.
Thus, the invention further provides a pharmaceutical composition comprising as active ingredient at least one compound of formula I as defined above (preferably less than 80%, and more preferably less than 50% by weight) in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
Examples of suitable adjuvants, diluents or carriers are: for tablets, capsules and dragees - microcrystalline cellulose, calcium phosphate, diatomaceous earth, a sugar such as lactose, dextrose or mannitol, talc, stearic acid, starch, sodium bicarbonate and/or gelatin; for suppositories - natural or hardened oils or waxes; and for inhalation compositions - coarse lactose. The compound of formula I is preferably in a form having a mass median diameter of from 0.01 to 10 microns. The compositions may also contain suitable preserving, stabilising and wetting agents, solubilisers, sweetening and colouring agents and flavourings. The compositions may, if desired, be formulated in sustained release form.
For the above-mentioned therapeutic uses the dosage administered will vary with the compound employed, the mode of administration and the disease indicated. However, in general, satisfactory results are obtained when the compounds are administered at a dosage which produces a concentration in the blood stream of from l-100μg/ml, preferably 5-100μg/ml.
For man the indicated total daily dosage is in the range of from lmg to 2500mg and preferably from lOmg to 2000mg, which may be administered, for example twice weekly, or in divided doses from 1 to 6 times a day or in sustained release form. Thus unit dosage forms suitable for administration, eg oesophageally, comprise from lmg to 2500mg, and preferably 2mg to 2000mg of the compound preferably admixed with a solid or liquid pharmaceutically acceptable diluent, carrier or adjuvant. According to a further aspect of the present invention there is provided a method of treatment or prophylaxis of a disease caused by an enveloped virus, which comprises administration of a therapeutically effective amount of a compound of formula I as defined above to a patient suffering from or at risk of contracting such a disease. The compounds of formula I have the advantage that they are less toxic, more efficacious, are longer acting, have a broader range of activity, are more potent, produce fewer side effects, are more easily absorbed or have other useful pharmacological properties, than compounds previously used against the diseases mentioned above.
The antiviral activity of the compounds of formula I which may be used in the present invention were tested in the procedures set out in Tests A and B below. Test A
Mammalian lymphocyte (H9IIIB) cells which were chronically infected with HIV were diluted to a concentration of 2xl05ml"1 in a culture medium (RPMI 1640 - which is a mixture of amino acids, salts, glucose and vitamins available from Gibco) . 0.5ml aliguots of this solution were placed in the wells of a tissue culture plate together with 0.5ml aliguots of an aqueous solution of "the compound under test. A range of initial concentrations of test compound solution were used (0.4, 4, 40 and 400mgml_1) , thus giving final test compound concentrations of 0.1, 1, 10 and lOOmgml-1 in the wells. Uninfected human lymphocyte (8166) cells (1ml of a lxl06ml_1 solution in a culture medium) were then added to some wells, and culture medium alone (1ml) was added to the remaining wells.
The infected cell/test compound mixtures were then incubated at 37βC. On following days, for example day 1 and day 4, 200μl samples of the supernatant liquor from each well were removed and tested for antigen P24, which is produced by the human immunodeficiency virus using the standard Coulter Antigen (P24) ELISA test. The presence of antigen P24 thus indicates the presence of HIV.
The test described above gives an indication both of the test compound's inhibitory effect on virus release, and of the test compound's inhibitory effect on virus attachment and penetration. Test B
Mammalian lymphocyte (H9IIIB) cells which were chronically infected with HIV were diluted to a concentration of 2xl05ml~1 in a culture medium (RPMI
1640). l.Oml aliquots of this solution were placed in the wells of a tissue culture plate together with l.Oml aliquots of an aqueous solution of the compound under test. A range of initial concentrations of test compound solution were used (0.2, 2, 20 and 200mgml~1) , thus giving test compound concentrations of 0.1, 1, 10 and lOOmgml"1 in the wells.
The infected cell/test compound mixtures were then incubated at 37βC. On following days, for example day 1 and day 4, 200μl samples of the supernatant liquor from each well were removed and tested for antigen P24, which is produced by the human immunodeficiency virus. The presence of antigen P24 thus indicates the presence of HIV. The test described above gives an indication of the test compound's inhibitory effect on virus release.

Claims

1. A compound of formula I,
Figure imgf000010_0001
wherein
R1 and R2 both represent (H,α-OH) or both represent 0;
RJ represents (H,H) or O; and
R>4* represents OH or NH(CH2)2S03H; and pharmaceutically acceptable salts thereof; provided that i) when R1 and R2 both represent (H,α-0H) and R3 represents (H,H) , then R4 represents NH(CH2)2S03H; and ii) when 1 and R2 both represent O and R3 represents O, then R4 represents NH(CH2)2S03H; for use as a pharmaceutical.
2. The use of a compound of formula I as defined in claim 1, but without proviso (ii) , as active ingredient in the manufacture of a medicament for the treatment of diseases caused by an enveloped virus.
3. The use according to claim 2, wherein the disease is AIDS .
4. The use according to claim 2, wherein the disease is influenza or parainfluenza.
5. The use according to claim 2, wherein the disease is herpes.
6. The use according to any one of claims 2 to 5, wherein the compound of formula I is dehydrocholic acid.
7. The use according to any one of claims 2 to 5, wherein the compound of formula I is taurochenodeoxycholic acid.
8. A pharmaceutical composition comprising as active ingredient at least one compound of formula I as defined in claim 1 in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
9. A method of treatment or prophylaxis of a disease caused by an enveloped virus, which comprises administration of a therapeutically effective amount of a compound of formula I as defined in claim 2 to a patient suffering from or at risk of contracting such a disease.
PCT/GB1989/001080 1988-09-20 1989-09-14 Bile acids for treatment of viral infections Ceased WO1990003172A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1019900701043A KR900701278A (en) 1988-09-20 1989-09-14 Bile acids for the treatment of viral infections

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB8822012.4 1988-09-20
GB888822012A GB8822012D0 (en) 1988-09-20 1988-09-20 Method of treatment
GB888822015A GB8822015D0 (en) 1988-09-20 1988-09-20 Method of treatment
GB8822020.7 1988-09-20
GB888822020A GB8822020D0 (en) 1988-09-20 1988-09-20 Method of treatment
GB8822015.7 1988-09-20

Publications (2)

Publication Number Publication Date
WO1990003172A2 true WO1990003172A2 (en) 1990-04-05
WO1990003172A3 WO1990003172A3 (en) 1990-06-28

Family

ID=27264092

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1989/001080 Ceased WO1990003172A2 (en) 1988-09-20 1989-09-14 Bile acids for treatment of viral infections

Country Status (6)

Country Link
EP (2) EP0435926A1 (en)
JP (1) JPH04500670A (en)
KR (1) KR900701278A (en)
AU (1) AU4328189A (en)
PT (1) PT91745B (en)
WO (1) WO1990003172A2 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994000126A1 (en) * 1992-06-30 1994-01-06 Montefarmaco S.P.A. The use of bile acids as antiviral agents
DE4316347C1 (en) * 1993-02-26 1994-08-18 Ina Dr Levi Process for the preparation of a pharmaceutical preparation and use thereof for the treatment of certain diseases
US5635612A (en) * 1993-02-23 1997-06-03 The Trustees Of Princeton University Method of forming multiple glycosidic linkages in a single step
US5700916A (en) * 1993-02-23 1997-12-23 Trustees Of Princeton University Solution and solid-phase formation of glycosidic linkages
CN115414370A (en) * 2022-10-14 2022-12-02 华中农业大学 Application of sodium taurocholate in preparing medicine for treating or preventing influenza virus infection

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5846964A (en) * 1993-07-19 1998-12-08 Tokyo Tanabe Company Limited Hepatitis C virus proliferation inhibitor
US9136083B2 (en) 2013-03-15 2015-09-15 Regal Beloit America, Inc. Enclosed bus bar fuse holder
JP2025014084A (en) * 2021-12-07 2025-01-29 慶應義塾 Virus proliferation inhibitors

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3591687A (en) * 1968-03-13 1971-07-06 George A Bray Bile acids and derivatives thereof as anorectic agents
BE792826A (en) * 1971-12-16 1973-03-30 Intellectual Property Dev Corp COMPOSITION AND METHOD FOR REDUCING THE LEVELS OF CHOLESTEROL AND LIPIDS IN MAMMALS
IT1101649B (en) * 1978-12-15 1985-10-07 Lehner Ag PROLONGED ACTION PHARMACEUTICAL COMPOSITION CONTAINING BILE ACIDS
AU2272883A (en) * 1982-12-22 1984-06-28 Herpes Pharmaceutical Inc. Pharmaceutical compositions of steriods for treatment of herpes simplex infections
GB8417895D0 (en) * 1984-07-13 1984-08-15 Marples B A Pharmaceutical anti-fungal composition
GB8706313D0 (en) * 1987-03-17 1987-04-23 Health Lab Service Board Treatment & prevention of viral infections
JPH06302932A (en) * 1993-04-09 1994-10-28 Toyo Electric Mfg Co Ltd Printed wiring board

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994000126A1 (en) * 1992-06-30 1994-01-06 Montefarmaco S.P.A. The use of bile acids as antiviral agents
US5635612A (en) * 1993-02-23 1997-06-03 The Trustees Of Princeton University Method of forming multiple glycosidic linkages in a single step
US5639866A (en) * 1993-02-23 1997-06-17 Princeton University Single-step formation of multiple glycosidic linkages
US5700916A (en) * 1993-02-23 1997-12-23 Trustees Of Princeton University Solution and solid-phase formation of glycosidic linkages
US5792839A (en) * 1993-02-23 1998-08-11 Trustees Of Princeton University Catalytic method of forming a glycosidic linkage
US5861492A (en) * 1993-02-23 1999-01-19 The Trustees Of Princeton University Solution and solid-phase formation of glycosidic linkages
US6194393B1 (en) * 1993-02-23 2001-02-27 The Trustees Of Princeton University Solution and solid-phase formation of glycosidic linkages
DE4316347C1 (en) * 1993-02-26 1994-08-18 Ina Dr Levi Process for the preparation of a pharmaceutical preparation and use thereof for the treatment of certain diseases
CN115414370A (en) * 2022-10-14 2022-12-02 华中农业大学 Application of sodium taurocholate in preparing medicine for treating or preventing influenza virus infection

Also Published As

Publication number Publication date
PT91745B (en) 1995-05-31
AU4328189A (en) 1990-04-18
JPH04500670A (en) 1992-02-06
EP0435926A1 (en) 1991-07-10
WO1990003172A3 (en) 1990-06-28
PT91745A (en) 1990-03-30
EP0365139A2 (en) 1990-04-25
KR900701278A (en) 1990-12-01
EP0365139A3 (en) 1990-08-01

Similar Documents

Publication Publication Date Title
US4933169A (en) Antiviral inhalation therapy
AU778967B2 (en) Treatments based on discovery that nitric oxide synthase is a paraquat diaphorase
WO1999025357A1 (en) USE OF 9-DEOXY-2', 9-α-METHANO-3- OXA-4,5,6- TRINOR-3, 7-(1',3'-INTERPHENYLENE) -13,14-DIHYDRO- PROSTAGLANDIN F1 TO TREAT PERIPHERAL VASCULAR DISEASE
JP2904827B2 (en) Use of trifluoromethylphenyltetrahydropyridine in the preparation of a pharmaceutical composition useful for treating anxiety and anxiety-depressive disorders
US5554655A (en) Method of treating HIV infection
EP0607252B1 (en) Compositions for the treatment of hiv infection
IL105090A (en) N-(phosphonoacetyl)-l-aspartic acid as broad spectrum antiviral
WO1990003172A2 (en) Bile acids for treatment of viral infections
EA017705B1 (en) Method for inhibiting orthopoxvirus infections
AU728461B2 (en) Pharmaceutical compositions
JPS63145279A (en) Drug product
GB2162745A (en) Nasal compositions
Hostetler et al. Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice
DE60032915T2 (en) GALLIUM COMPLEXES OF 3-HYDROXY-4-PYRONES FOR THE TREATMENT OF INFECTIONS CAUSED BY INTRA-CELLULAR PROCYNOTES, DNA AND RETRO VIRUSES
KR0143410B1 (en) Phamaceutical composition for the treatment of hepatitis-b infections
CA1092510A (en) Compositions containing 5'-amino-5' deoxythymidine and pharmaceutically acceptable salts thereof
EP0183352A2 (en) Use of suramin for clinical treatment of infection with any of the members of the family of human-t-cell leukemia (htvl) viruses including lymphadenopathy virus (lav)
IE44580B1 (en) Therapeutic compositions and use thereof
US4436732A (en) Medicated compound for treating diseases infected by virus of the herpes group
KR100227095B1 (en) Anti-hiv agent
US5955498A (en) Agent for prophylaxis and therapy of diseases
EP0082667A1 (en) Pharmaceutical compositions
CA2167841A1 (en) Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes
US4230725A (en) Antiviral agent
US5612319A (en) Postexposure prevention of HIV infection or seroconversion

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AU BB BG BR DK FI HU JP KP KR LK MC MG MW NO RO SD SU US

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE BF BJ CF CG CH CM DE FR GA GB IT LU ML MR NL SE SN TD TG

AK Designated states

Kind code of ref document: A3

Designated state(s): AU BB BG BR DK FI HU JP KP KR LK MC MG MW NO RO SD SU US

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE BF BJ CF CG CH CM DE FR GA GB IT LU ML MR NL SE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 1989910885

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1989910885

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1989910885

Country of ref document: EP