MODIFIED FLUORINATED NUCLEOSIDE ANALOGUES

• US 20080070861A1
• Filed: 09/12/2007
• Published: 03/20/2008
• Est. Priority Date: 05/30/2003
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Pharmasset Incorporated (Gilead Sciences Inc.)
• Inventors: CLARK, JEREMY
• Granted Patent: US 10,287,311 B2
• Time in Patent Office: Days
• US Class Current: 514/49
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/048 Pyridine radicals
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals

Abstract

The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Claims

1-129. -129. (canceled)

130. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D or β

-L) or its pharmaceutically acceptable salt of the structure;

wherein

R¹ and R⁷ are independently H, a monophosphate, a diphosphate, a triphosphate, a H-phosphonate, an alkyl, an alkyl sulfonyl, or an arylalkyl sulfonyl; and

R⁴ is NH₂ or OH.

131. The method for the treatment of hepatitis C infection of claim 130, wherein R⁷ is H and R¹ is a monophosphate, a diphosphate, or a triphosphate.

132. The method for the treatment of hepatitis C infection of claim 130, wherein R⁷ is H and R¹ is a diphosphate, or a triphosphate.

133. The method for the treatment of hepatitis C infection of claim 130, wherein R⁷ is H and R¹ is a triphosphate.

134. The method for the treatment of hepatitis C infection of claim 130, wherein R¹ and R⁷ are H.

144. The method of as recited in any one of claims 130-143, wherein the antivirally effective amount of the nucleoside is administered in combination or alternation with at least one treatment selected from among an antiviral treatment, an antibacterial treatment, an anticancer treatment, and interferon.

135. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D) or its pharmaceutically acceptable salt thereof of the formula;

136. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D) or its pharmaceutically acceptable salt thereof of the formula;

137. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of a pharmaceutical composition comprising

a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D or β

-L) or its pharmaceutically acceptable salt of the structure;

wherein

R¹ and R⁷ are independently H, a monophosphate, a diphosphate, a triphosphate, a H-phosphonate, an alkyl, an alkyl sulfonyl, or an arylalkyl sulfonyl; and

R⁴ is NH₂ or OH;

and

a pharmaceutically acceptable carrier.

138. The method for the treatment of hepatitis C infection of claim 137, wherein R⁷ is H and R¹ is a monophosphate, a diphosphate, or a triphosphate.

139. The method for the treatment of hepatitis C infection of claim 137, wherein R⁷ is H and R¹ is a diphosphate, or a triphosphate.

140. The method for the treatment of hepatitis C infection of claim 137, wherein R⁷ is H and R¹ is a triphosphate.

141. The method for the treatment of hepatitis C infection of claim 137, wherein R¹ and R⁷ are H.

142. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of

a pharmaceutical composition comprising a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D) or its pharmaceutically acceptable salt thereof of the formula;

and

a pharmaceutically acceptable carrier.

143. A method for the treatment of hepatitis C infection, which comprises:

administering to a mammal in need thereof an antivirally effective amount of a pharmaceutical composition comprising

a (2′

R)-2′

-deoxy-2′

-fluoro-2′

-C-methyl nucleoside (β

-D) or its pharmaceutically acceptable salt thereof of the formula;

and

a pharmaceutically acceptable carrier.