Methods and compositions for treating flaviviruses and pestiviruses

• US 20070037773A1
• Filed: 09/25/2006
• Published: 02/15/2007
• Est. Priority Date: 05/26/2000
• Status: Active Grant

• Current Assignee: Idenix Pharmaceuticals (Merck & Co., Inc.)
• Original Assignee: Jean-Pierre Sommadossi, Paulo Lacolla
• Inventors: Sommadossi, Jean-Pierre, LaColla, Paulo
• Granted Patent: US 8,343,937 B2
• Time in Patent Office: Days
• US Class Current: 514/45
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• 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: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Claims

1-85. -85. (canceled)

86. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula X, XI or XII:

87-129. -129. (canceled)

130. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound selected from the group consisting of

134. The pharmaceutical composition of claim 130, wherein the compound is selected from the group consisting of

135. The pharmaceutical composition of claim 130, wherein the compound is selected from the group consisting of

136. The pharmaceutical composition of claim 134, wherein the compound has the structure:

137. The pharmaceutical composition of claim 134, wherein the compound has the structure:

138. The pharmaceutical composition of claim 134, wherein the compound has the structure:

139. The pharmaceutical composition of claim 135, wherein the compound has the structure:

140. The pharmaceutical composition of claim 135, wherein the compound has the structure:

141. The pharmaceutical composition of claim 135, wherein the compound has the structure:

142. The pharmaceutical composition of claim 134, wherein the compound has the structure:

143. The pharmaceutical composition of claim 134, wherein the compound has the structure:

144. The pharmaceutical composition of claim 134, wherein the compound has the structure:

145. The pharmaceutical composition of claim 135, wherein the compound has the structure:

146. The pharmaceutical composition of claim 135, wherein the compound has the structure:

147. The pharmaceutical composition of claim 135, wherein the compound has the structure:

148. The pharmaceutical composition as described in any of the preceding claims 130-147, wherein the said compound is in the form of a dosage unit.

149. The pharmaceutical composition as described in claim 148, wherein the dosage unit contains 10 to 1500 mg of said compound.

150. The pharmaceutical composition as described in claim 148 or 149, wherein said dosage unit is a tablet or capsule.

151. The pharmaceutical composition of any one of claims 130-150, wherein the compound is combined with a pharmaceutically acceptable carrier.

152. The pharmaceutical composition of claim 151, wherein the carrier is suitable for oral delivery.

153. The pharmaceutical composition of claim 151, wherein the carrier is suitable for intravenous, parenteral, intradermal, subcutaneous or topical delivery.

166. The method of any of the preceding claims 151-165, wherein the said compound is in the form of a dosage unit.

167. The method of claim 166, wherein the dosage unit contains 10 to 1500 mg of said compound.

168. The method of claim 166 or 167, wherein said dosage unit is a tablet or capsule.

169. The method of any one of claims 151-165, wherein the compound is combined with a pharmaceutically acceptable carrier.

170. The method of claim 169, wherein the carrier is suitable for oral delivery.

171. The method of claim 170, wherein the carrier is suitable for intravenous, parenteral, intradermal, subcutaneous or topical delivery.

131. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVI:

132. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVII:

133. A pharmaceutical composition for the treatment or prophylaxis of a flavivirus or pestivirus in a host, comprising an effective amount of a compound of Formula XVIII:

154. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of selected from the group consisting of

158. The method of claim 154, wherein the compound is selected from the group consisting of

159. The method of claim 154, wherein the compound is selected from the group consisting of

160. The method of claim 158, wherein the compound has the structure:

161. The method of claim 158, wherein the compound has the structure:

162. The method of claim 158, wherein the compound has the structure:

163. The method of claim 159, wherein the compound has the structure:

164. The method of claim 159, wherein the compound has the structure:

165. The method of claim 159, wherein the compound has the structure:

155. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVI:

156. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVII:

157. A method for the treatment or prophylaxis of a flavivirus or pestivirus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula XVIII: