Nucleoside compounds and uses thereof

• US 6,815,542 B2
• Filed: 12/13/2002
• Issued: 11/09/2004
• Est. Priority Date: 06/16/2000
• Status: Expired due to Term

• Current Assignee: Valeant Research & Development (Bausch Health Cos., Inc.)
• Original Assignee: Ribapharm Inc. (Bausch Health Cos., Inc.)
• Inventors: Girardet, Jean-Luc, Hong, Zhi, Lau, Johnson, Ramasamy, Kanda
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Owens, Jr., Howard V.
• Application Number:
  US10/318,476
• Publication Number:
  US 20040002596A1
• Time in Patent Office: 697 Days
• Field of Search: 536/28.6, 536/28.7, 536/28.8
• US Class Current: 536/28.6
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: C07H 19/052 Imidazole radicals
• CPC Class Codes: C07H 19/056 Triazole or tetrazole radicals

Abstract

Nucleosides, novel nucleoside analog compounds and their novel prodrug forms are disclosed. The novel compounds, prodrugs, or pharmaceutically acceptable esters or salts thereof may be used in pharmaceutical compositions, and such compositions may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. The novel compounds may also be used to modulate aspects of the immune system, including modulation of Type 1 and Type 2 activity.

Claims

1. A nucleoside analog of Formula 1, in which the sugar is either in the L- or D-configuration:

wherein Z is O, CH₂, or S;

R is independently H, hydroxyl, protected hydroxyl or halogen;

R₁, R₂, R₃, R₄, R₅, are independently selected from H, halogen, CN, CH₂OH, lower alkyl, vinyl, and acetylene radical;

with the proviso that

when R₂ is hydroxyl, then, R that is attached to the same carbon as that of R₂ is not halogen;

when R₃ is hydroxyl, then, R that is attached to the same carbon as that of R₃ is not halogen;

R₆ is O-monoboranophosphate radical, O-diboranophosphate radical, O-triboranophosphate radical, O-monoboranophosphate derivative radical, O-diboranophosphate derivative radical, or O-triboranophosphate derivative radical;

R₇ is selected from H, alkyl, CH₃COO—

, CH₃COO-phenyl-CH₂—

O—

CO—

, phenyl, —

(CH₂)n-COOH, coumarinic acid, salicylic acid, dithiosuccinoyl derivative radical, reductase mediated cleavable group, phosphonoformic acid radical, and phosphoramidate group radical;

R₈ is selected from H, H*HCl, H*HBr, lower alkyl, phenyl, CH₃COO—

, CH₃COO—

Phenyl-CH₂—

O—

CO—

, carbamate, and phenyl; and

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.

2. A nucleoside analog of Formula 2, in which the sugar is either in the L- or D-configuration:

wherein X is O or NH;

R₁ is a masking group of the amino group;

R₂ is monoboranophosphate radical, diboranophosphate radical, triboranophosphate radical, monoboranophosphate derivative radical, diboranophosphate derivative radical, triboranophosphate derivative radical, monophosphate radical, diphosphate radical, triphosphate radical, stabilized monophosphate radical, stabilized diphosphate radical, or stabilized triphosphate radical;

R₃ is independently H or C₁-C₁₈ acyl; and

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.

3. The nucleoside analog of claim 2 having a structure according to Formula 3:

where R₁ is a masking group having any of the following structures;

where X is O or S;

Z is R₂ is monoboranophosphate radical, diboranophosphate radical, triboranophosphate radical, stabilized monophosphate radical, stabilized diphosphate radical, or stabilized triphosphate radical;

R is straight or branched C₁-C₁₈ alkyl, alkenyl, alkynyl, aryl, or aralkyl; and

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.

4. A nucleoside analog of Formula 4, in which the sugar is either in the L- or D-configuration:

wherein Y is O or NH;

wherein R₁ is H or a masking group as designated in claim 3;

R₂ is H, phosphate radical to form a diphosphate, diphosphate radical to form a triphosphate, or a masking group of the phosphate having any of the following structures;

where X is O, or S;

R is straight or branched C₁-C₁₈ alkyl, alkenyl, alkynyl, aryl, or aralkyl; and

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.

5. A nucleoside analog of Formula 5, in which the sugar is either in the L- or D-configuration:

wherein Y is O or NH;

wherein X is R₂ is monoboranophosphate radical, diboranophosphate radical, triboranophosphate radical, monoboranophosphate derivative radical, diboranophosphate derivative radical, triboranophosphate derivative radical, stabilized monophosphate radical, stabilized diphosphate radical, or stabilized triphosphate radical; and

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.

6. A nucleoside analog of Formula 6, in which the sugar is either in the L- or D-configuration:

wherein the nucleoside analog optionally forms a pharmacologically acceptable salt with an acid or a base.