US2016083413A1PendingUtilityA1

2'-chloro nucleoside analogs for hcv infection

42
Assignee: IDENIX PHARMACEUTICALS INCPriority: Oct 8, 2012Filed: Oct 22, 2015Published: Mar 24, 2016
Est. expiryOct 8, 2032(~6.2 yrs left)· nominal 20-yr term from priority
A61P 31/04A61P 31/14A61P 43/00C07H 19/06A61K 31/403A61K 31/497A61P 1/16C07H 19/11C07H 19/213C07H 19/23A61K 31/7105A61K 31/7072C07H 19/16A61K 31/7068A61K 38/212A61K 31/706A61K 45/06A61K 31/7064C07H 19/14C07H 19/20C07H 19/12A61K 31/7076A61K 31/708C07H 19/10
42
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Claims

Abstract

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

Claims

exact text as granted — not AI-modified
1 - 2 . (canceled) 
     
     
         3 . A compound according to Formula III: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof; 
         wherein B is a nucleobase; 
         R 1  is phenyl; 
         X is an N-linked amino acid ester; and 
         W is O. 
       
     
     
         4 - 41 . (canceled) 
     
     
         42 . The compound according to  claim 3 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         43 . The compound according to  claim 42 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
       
     
     
         44 . The compound according to  claim 3 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         45 . The compound according to  claim 44 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The compound according to  claim 3 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         47 . The compound of  claim 46 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         48 . A nucleoside composition comprising a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein said compound is a designated enantiomer and said composition is substantially free of other stereoisomers of said compound. 
       
     
     
         49 . A pharmaceutical composition comprising a compound of  claim 3  or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof; and a pharmaceutically acceptable carrier. 
     
     
         50 . The pharmaceutical composition according to  claim 49 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         51 . The pharmaceutical composition according to  claim 50 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
       
     
     
         52 . The pharmaceutical composition according to  claim 49 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         53 . The pharmaceutical composition according to  claim 52 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         54 . The pharmaceutical composition according to  claim 53 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound. 
     
     
         55 . The pharmaceutical composition according to  claim 49 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         57 . The pharmaceutical composition according to  claim 56 , wherein said compound is a designated enantiomer, and said composition is substantially free of other stereoisomers of said compound. 
     
     
         58 . A method for the treatment of a human infected with a hepatitis C virus, comprising the administration to said human an effective amount of a compound according to  claim 3  or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
     
     
         59 . The method according to  claim 58 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         60 . The method according to  claim 59 , wherein said compound is according to the structure: 
       
         
           
           
               
               
           
         
       
     
     
         61 . The method according to  claim 58 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         62 . The method according to  claim 61 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         63 . The method according to  claim 58 , wherein said compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof. 
       
     
     
         64 . The method according to  claim 63 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         65 . The method of  claim 58 , wherein the compound is administered in combination with a second anti-viral agent selected from the group consisting of an interferon, a nucleotide analogue, a polymerase inhibitor, an NS3 protease inhibitor, an NS5A inhibitor, an entry inhibitor, a non-nucleoside polymerase inhibitor, a cyclosporine immune inhibitor, an NS4A antagonist, an NS4B-RNA binding inhibitor, a locked nucleic acid mRNA inhibitor, a cyclophilin inhibitor, and combinations thereof. 
     
     
         66 . The method of  claim 65 , wherein said compound is 
       
         
           
           
               
               
           
         
       
     
     
         67 . The method of  claim 66 , wherein said second anti-viral agent is an NS3 protease inhibitor. 
     
     
         68 . The method of  claim 66 , wherein said second anti-viral agent is an NS5A inhibitor.

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