RU2002112250A - Compositions and methods for L-nucleosides, L-nucleotides and their analogues - Google Patents

Claims (53)

1. The compound having the structure

where R represents PO $\genfrac{}{}{0ex}{}{\text{2-}}{\text{3}}$ , (PO ₃ ) $\genfrac{}{}{0ex}{}{\text{3-}}{\text{2}}$ or (PO ₃ ) $\genfrac{}{}{0ex}{}{\text{4-}}{\text{3}}$ . 2. The compound having the structure

3. The compound having the structure

where W is —N (R ₁ ) (R ₂ ) or = Nr ₁ , where R ₁ and R _{2 are} independently hydrogen, linear alkyl, branched alkyl, alkenyl, alkynyl, aralkyl. aralkenyl, aralkinyl or aryl. 4. The compound according to claim 3, where R ₁ or R ₂ independently additionally contains a nitrogen atom, an oxygen atom, a sulfur atom or a halogen atom. 5. A method of treating a viral infection in a patient, wherein a composition is administered that comprises a compound according to claim 1, 2 or 3 in a dosage effective to inhibit the propagation of the virus. 6. The method according to claim 5, where the dosage is from 50 to 500 mg / day. 7. The method according to claim 5, where the dosage is from 500 to 2500 mg / day. 8. The method according to claim 5, where the viral infection is selected from the group consisting of human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, respiratory syncytial virus (RSV) infection, influenza virus infections; and parainfluenza virus infections. 9. The method according to claim 5, wherein the patient is additionally co-administered with a cytokine. 10. The method according to claim 9, where the cytokine is interferon. 11. The method of claim 10, where the interferon is interferon alpha-2b. 12. The method according to claim 5, in which Ribavirin is additionally administered. 13. The compound according to claim 1, where R represents PO $\genfrac{}{}{0ex}{}{\text{2-}}{\text{3}}$ . 14. A method of treating a viral infection in a patient, wherein a composition is jointly administered containing the compound of claim 13 in a dosage effective to inhibit the multiplication of the virus. 15. The compound according to claim 1, where R represents (PO ₃ ) $\genfrac{}{}{0ex}{}{\text{3-}}{\text{2}}$ . 16. A method of treating a viral infection in a patient, wherein a composition is administered containing the compound of claim 15 in a dosage effective to inhibit the multiplication of the virus. 17. The compound according to claim 1, where R represents (PO ₃ ) $\genfrac{}{}{0ex}{}{\text{4-}}{\text{3}}$ . 18. A method for treating a viral infection in a patient, wherein a composition is administered containing the compound of claim 17 in a dosage effective to inhibit the multiplication of the virus. 19. A method of increasing the selectivity of a pharmacologically active molecule with respect to the pharmacological effect in the target cell, in which: take a medicine, and this medicine is 1-β-L-ribofuranosyl-1,2,4-triazole-3-carboxamide; modifying said drug with a modifying group, said modifying group being covalently attached to the drug via a nitrogen atom; and moreover, this modifying group is enzymatically removed from the drug in the target cell. 20. The method according to claim 19, where the modifying group is = NH, and where this modifying group covalently binds to the carbonyl atom in the drug. 21. The method according to claim 19, where the modifying group is —N (R ₁ ) (R ₂ ) or = NR ₁ , where R ₁ and R ₂ independently represent hydrogen, linear alkyl, branched alkyl, alkenyl, alkynyl, aralkyl , aralkenyl, aralkinyl or aryl. 22. The method according to item 21, where R ₁ or R ₂ independently additionally contains a nitrogen atom, an oxygen atom, a sulfur atom or a halogen atom. 23. A method of treating a disease characterized by inflammation of an organ in a patient, wherein: take the compound according to claim 1; and this compound is administered to the patient in a dosage that: (a) induces systemic immunomodulation and non-systemic immunosuppression of Type I and Type II responses, and (b) causes immunosuppression of Type I and Type II responses in the indicated organ of the patient. 24. A method of treating a disease characterized by inflammation of an organ in a patient, wherein: take the compound according to claim 2; and this compound is administered to the patient in a dosage that: (a) induces systemic immunomodulation and non-systemic immunosuppression of Type I and Type II responses, and (b) causes immunosuppression of Type I and Type II responses in the indicated organ of the patient. 25. A method of treating a disease characterized by inflammation of an organ in a patient, wherein: take the compound according to claim 3; and administer to the patient this compound in a dosage that: (a) causes systemic immunomodulation and non-systemic immunosuppression of Type I responses and Type II, and (b) causes immunosuppression of the responses of Type 1 and Type II in the specified organ of the patient. 26. The method according to any one of claims 23-25, wherein said organ is a liver, and where the liver is infected with a virus. 27. The method according to any one of p, where the virus is a hepatitis C virus (HCV). 28. A method of stimulating neuronal growth, in which: recognize that a compound having structure I is effective for stimulating neuronal growth in a given concentration range;

where Y is 1-β-L-ribofuranosyl, 1-β-L-ribofuranosyl-5-phosphate, 1-β-1-ribofuranosyl-5-diphosphate, 1-β-L-ribofuranosyl-5-triphosphate, 1- β-D-ribofuranosyl, 1-β-D-ribofuranosyl-5-phosphate, 1-β-D-ribofuranosyl-5-diphosphate or 1-β-D-ribofuranosyl-5-triphosphate; and supply neurons with the indicated compound in a given concentration range. 29. The method of claim 28, wherein the compound is ribavirin. 30. The method according to p, where the compound is a phosphorylated ribavirin. 31. The method of claim 28, wherein the compound is Levovirin ™. 32. The method according to p, where the compound is a phosphorylated Levovirin ™. 33. The method of claim 28, wherein said compound is administered as part of a treatment of a patient’s disease in a dosage range effective to increase the Type 1 response and reduce the Type 2 response in the patient. 34. The method according to p, in which additionally carry out targeted delivery to unipolar neuronal cells among neurons. 35. The method according to p, in which additionally carry out targeted delivery to bipolar neuronal cells among neurons. 36. The method according to p. where neurons are part of neuronal tissue that includes at least four of the following cell types: astrocyte, dendrocyte, myelin sheath cell, neuroglia cell, unipolar neuronal cell, bipolar neuronal cell, multipolar neuronal cell and receptor cell. 37. An antiviral drug composition comprising a first compound having a direct antiviral effect and an indirect antiviral effect; and a second compound that increases the overall antiviral effect, wherein this general antiviral effect includes a direct antiviral effect and an indirect antiviral effect, and wherein said second compound specifically binds a hapten selected from the group consisting of a viral protein and a cytokine. 38. The antiviral drug composition according to clause 37, where the first compound is a nucleoside analogue. 39. The antiviral drug composition according to clause 37, where the nucleoside analogue is ribavirin. 40. The antiviral drug composition according to clause 37, where the nucleoside analogue is Levovirin ™. 41. The antiviral drug composition according to clause 37 or clause 38, where the nucleoside analogue is in the form of a prodrug. 42. The antiviral drug composition according to clause 37, where the direct antiviral effect includes inhibition of viral replication. 43. The antiviral drug composition according to clause 37, where the indirect antiviral effect includes a shift in the balance of Type 1 / Type 2 in the direction of the response of Type 1. 44. The antiviral drug composition according to clause 37, where the indirect antiviral effect includes suppression of the response of Type 1 and Type 2. 45. The antiviral drug composition according to clause 37, where the second compound is an antibody. 46. The antiviral drug composition of claim 45, wherein the antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a synthesized antibody, and an antibody fragment. 47. The antiviral drug composition according to clause 37, where the viral protein is a protein of a virus selected from the group consisting of human immunodeficiency virus (HIV), hepatitis virus, influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). 48. The antiviral drug composition according to clause 37, where the viral protein is a reverse transcriptase. 49. The antiviral drug composition according to clause 37, where the cytokine is a Type 1 cytokine. 50. The antiviral drug composition according to clause 37, where the first compound and the second compound have a synergistic effect. 51. The antiviral drug composition of claim 37, wherein at least one of said first compound and second compound selectively accumulates in an organ. 52. The antiviral drug composition of claim 51, wherein said organ is selected from the group consisting of a liver and a brain. 53. The antiviral drug composition of claim 37, wherein the first compound is Ribavirin and the second compound is an antibody that specifically binds a Type 2 cytokine.