Nucleoside compounds

• US 6,495,677 B1
• Filed: 06/16/2000
• Issued: 12/17/2002
• Est. Priority Date: 02/15/2000
• Status: Expired due to Term

• Current Assignee: Valeant Pharmaceuticals North America LLC (Bausch Health Cos., Inc.)
• Original Assignee: Guangyi Wang, Johnson Lau, Kanda S. Ramasamy
• Inventors: Lau, Johnson, Wang, Guangyi, Ramasamy, Kanda S.
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Crane, Lawrence E
• Application Number:
  US09/594,410
• Time in Patent Office: 914 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/052 Imidazole radicals
• CPC Class Codes: C07H 19/056 Triazole or tetrazole radicals
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine 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 compound of Formula 1, in which the sugar is either in 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 selected from H, hydroxyl, protected hydroxyl, —

CH₂OH, —

CH₂PO(OH)₂—

, O-amino acid radical, O-retinoic acid, O-cholesterol, O-cholic acid, O-coumarinic acid, O-salicylic acid, O-succinic acid, O-bile acid radical, O—

P(O)—

(O—

CH₂—

CH₂—

S—

CO—

CH₃)₂;

O-steroid radical;

O-monophosphate derivative radical, O-diphosphate derivative radical, and O-triphosphate 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—

, and phenyl;

with the proviso that R₇ and R₈ are not H at the same time.

2. A nucleoside analog compound of Formula 3, 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 selected from H, HCO—

, R—

C(O)—

, and (R′

O)₂P(O)—

O—

, where R is a C₁-C₁₇ alkyl, alkenyl, or alkynyl group, and R′

is a masking group of the phosphate;

R₃ is independently H or C₁-C₁₈ acyl; and

R₁ and R₂ are not hydrogen at the same time.

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

where R₁ is H or a masking group as designated in claim 2;

R₂ is a masking group of the phosphate having any of the following structures;

where X is O, or S; and

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

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

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

where X is O or S; and

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

5. A nucleoside analog compound of Formula 7, in which the sugar is either in L- or D-configuration:

6. A nucleoside analog compound of Formula 10, in which the sugar is either in the L- or D-configuration:

wherein R is selected from hydrogen, halogen, amide, amidine, alkyl, phenyl, vinyl, and acetylene radical.

7. A nucleoside analog compound of Formula 11, in which the sugar is either in the L- or D- configuration:

wherein X is selected from oxygen, sulphur, Se, and NR; and

R is selected from hydrogen, acetyl, and alkyl.