Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1997-05-02
1999-10-05
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
588166, 588169, 588170, 588172, 588174, 544 2, 544 5, 544 8, 544 53, 544 57, 544 65, 544 66, 544 88, 544 98, 544157, 544179, 544182, 544214, 544232, 544243, 544337, 546 22, A61K 31685, C07F 902, C07F 906, C07F 928
Patent
active
059624370
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates generally to the treatment of viral infections, and more specifically to the treatment of viral infections with phospholipids and phospholipid derivatives.
BACKGROUND OF THE INVENTION
A current treatment for combating human immunodeficiency virus type 1 (HIV-1) infections is the administration of the nucleoside analog 3'-azido-3'-deoxythymidine (AZT) to an afflicted subject. See, eg., U.S. Pat. No. 4,724,232 to Rideout et al. HIV-1 infection treatment methods have also included the administration of ether lipid compounds in an amount effective to inhibit replication of the virus in infected cells, see, e.g., Kucera et al., AIDS Research and Human Retroviruses 6:491 (1990), and ether lipids conjugated with AZT and other antiviral nucleoside analogs. See PCT Application No. US91/04289 (published Dec. 26, 1991). These compounds appear to act at the plasma membrane to block the endocytic process of HIV-1 into CD4.sup.+ cells and the process of virus assembly, cell fusion and pathogenesis. They also can inhibit the activity of protein kinase C. Given the seriousness of HIV-1 infection worldwide, there is an ongoing need for new methods of combating HIV-1 infections.
Another virus of serious concern, hepatitis B virus (HBV), is one of a family of hepadnaviruses that cause acute and chronic liver disease, including liver cancer. HBV, which is found in the body fluids of infected persons, makes three antigenic proteins during multiplication in liver cells: hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). These three virus antigenic proteins are important as markers for determining virus infection, as antibodies against the virus infection are made in response to these virus proteins in the blood. An HBV vaccine is available to prevent infection, and hyperimmune gamma globulin is available for temporary prophylaxis against developing HBV infection in persons at risk. Clearly specific antiviral agents are needed for treatment and control of HBV infections in humans.
Based on the foregoing, it is an object of the present invention to provide a new treatment method for combating the effects of HIV-1.
It is another object of the present invention to provide compounds and pharmaceutical compositions for carrying out HIV-1 treatment methods.
It is also an object of the present invention to provide a new treatment method for combating the effects of HBV.
It is a second object of the present invention to provide compounds and pharmaceutical compositions for carrying out HBV treatment methods.
SUMMARY OF THE INVENTION
These and other objects are satisfied by the present invention, which provides methods of combating viral infections. As a first aspect, the present invention provides a method of combating a viral infection in a subject in need of such treatment comprising administering to the subject an effective infection-combating amount of a compound of Formula I or a pharmaceutical salt thereof. ##STR1## In the compounds of Formula I, R.sub.1 is a branched or unbranched, saturated or unsaturated C.sub.6 to C.sub.18 alkyl group optionally substituted from 1 to 5 times with --OH, --COOH, oxo, amine, or substituted or unsubstituted aromatic; X is selected from the group consisting of NHCO, CH.sub.3 NCO, CONH, CONCH.sub.3, S, SO, SO.sub.2, O, NH, and NCH.sub.3 ; R.sub.2 is a branched or unbranched, saturated or unsaturated C.sub.6 to C.sub.14 alkyl group optionally substituted from 1 to 5 times with --OH, --COOH, oxo, amine, or substituted or unsubstituted aromatic; Y is selected from the group consisting of NHCO, CH.sub.3 NCO, CONH, CONCH.sub.3, S, SO, SO.sub.2, O, NH, and NCH.sub.3 ; R.sub.6 is a branched or unbranched C.sub.2 to C.sub.6 alkyl group; and R.sub.3, R.sub.4, and R.sub.5 are independently methyl or ethyl, or R.sub.3 and R.sub.4 together form an aliphatic or heterocyclic ring having five or six members and R.sub.5 is methyl or ethyl. Preferred compounds include 1-dodecanamido-2-decyloxypropyl-3-phosphoch
REFERENCES:
patent: 2086585 (1937-07-01), Taub et al.
patent: 2087132 (1937-07-01), Taub et al.
patent: 2108765 (1938-02-01), Domagk
patent: 2209383 (1940-07-01), Bock
patent: 2439969 (1948-04-01), Fourneau
patent: 2445393 (1948-07-01), Fourneau
patent: 2513747 (1950-07-01), Sallman et al.
patent: 2606909 (1952-08-01), Blicke
patent: 2689790 (1954-09-01), Mowry et al.
patent: 2950253 (1960-08-01), Kling et al.
patent: 3054678 (1962-09-01), Michener et al.
patent: 3694473 (1972-09-01), Eibl et al.
patent: 4093714 (1978-06-01), Tolman et al.
patent: 4096278 (1978-06-01), Queuille
patent: 4119714 (1978-10-01), Kny et al.
patent: 4159988 (1979-07-01), Eibl et al.
patent: 4235877 (1980-11-01), Fullerton
patent: 4329302 (1982-05-01), Hanahan et al.
patent: 4426525 (1984-01-01), Hozumi et al.
patent: 4444766 (1984-04-01), Bosies et al.
patent: 4471113 (1984-09-01), Maccoss
patent: 4540521 (1985-09-01), Garst et al.
patent: 4619917 (1986-10-01), Lee et al.
patent: 4661509 (1987-04-01), Gordon et al.
patent: 4816450 (1989-03-01), Bell et al.
patent: 4826823 (1989-05-01), Cook et al.
patent: 4835263 (1989-05-01), Nguyen et al.
patent: 4837023 (1989-06-01), Eibl
patent: 4841039 (1989-06-01), Chu et al.
patent: 4880782 (1989-11-01), Eckstein et al.
patent: 5034394 (1991-07-01), Daluge
patent: 5116992 (1992-05-01), Braquet et al.
patent: 5138045 (1992-08-01), Cook et al.
Jia et al., Dismide Analogs of Phosphatidyl Choline as Potential Anti-AIDS Agents, J. Chem. Soc. Perkins Trans. I, No. 21, pp. 2521-2523, Nov. 7, 1993.
STN Printout for Van den Berg et al., Competitive Inhibition Of Lipolytic Enzymes. VI. Inhibition Of Two Human Phospholipases A2 By Acylamino Phospholipid Analogs, Biochim. Biophys. Acta, vol. 1124, No. 1, pp. 66-70, 1992.
STN Printout for De Haas et al., Competitive Inhibition Of Lipolytic Enzymes. IV. Structural Details Of Acylamino Phospholipid Analogs Important For The Potent Inhibitory Effects On Pancreatic Phospholipase A2, Biochim. Biophys. Acta. vol. 1046, No. 3, 1990.
Aggarwal, "Synthesis and Biological Evaluation of Prodrugs of Zidovudine", J. Med. Chem., 33, 1505-10 (1990).
Boldanova, et al., "Protective effect of Phosphatidylcholine-containing Liposomes in Experimental Toxic Hepatitis", Vopr. Med. Khim. 32, No. 3 (1986) Chemical Abstracts, 105, p. 67, Abstract No. 35587k (1986).
Bosies, et al., "Chemical Abstracts", 115CA:72142p 1991.
Chen, "Design and Synthesis of Novel Nucleoside Analogs as Potential Antiviral Agents", Abstract American Assoc. of Pharmaceutical Scientists, Orlando Fl., (1993).
Crumpton, "Novel Lipid Analogs with Cytostatic and Cytocidal Activity", Submitted to Anticancer Res., vol. 8, No. 6, pp. 1361-1366 (Nov.--Dec. 1988).
Daniel, "Alkyl-Linked Diglycerides Inhibit Protein Kinase C Activation by Diacylglycerols", Biochemical & Biophysical Res. Comm., 151, 291-97 (Feb. 29, 1988).
Dietzfelbinger, "Cytotoxic and Purging Effects of ET-18-OCH3 in Human Malignant Lymphoid Cell Lines in Vitro", Abstract 2472, Proceedings of the American Assoc. for Cancer Res., 31, 416 (Mar. 1990).
Fields, "Human Immunodeficiency Virus Induces Phosphorylation of its Cell Surface Receptor", Nature, 333, 278-80 (May 19, 1988).
Harada, "Infection of HTLV-III/LAV in HTLV-I-Carrying Cells MT-2 and MT-4 and Application in a Plaque Assay", Science, 229, 563-229 (Aug. 9, 1985).
Himmelmann, "Studies on the Cross Resistance Pattern of Membrane-Toxic Lipids in Vitro", Abstract 2448, Proceedings of the American Assoc. for Cancer Res., 31, 416 (Mar. 1990).
Hsu, L., et al., "Synthesis of Anti-Restricted Pyramidine Acyclic Nucleosides", Journal of Organic Chemistry, vol. 57, No. 12, pp. 3354-3358, (1992).
Kasnar, B., et al., Synthesis of 2',3'-Dideoxy-and 3'-Azido-2', 3'-Dideoxy-Pyridazine Nucleosides as Potential Antiviral Agents Nucleosides & Nucleotides, 13(1-3), pp. 359-479, (1994).
Korba, "Use of a Standardized Cell Culture Assay to Assess Activities of Nucleoside Analogs Against Hepatitus B Virus Replication", Antiviral Res., 19, 55-70 (1992).
Krugner-hig
Ishaq Khalid S.
Kucera Louis S.
Morris-Natschke Susan L.
Coleman Brenda
Raymond Richard L.
Wake Forest University
LandOfFree
Lipid analogs for treating viral infections does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Lipid analogs for treating viral infections, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lipid analogs for treating viral infections will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1171561