US2016016987A1PendingUtilityA1

Substituted nucleosides, nucleotides and analogs thereof

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Assignee: ALIOS BIOPHARMA INCPriority: Dec 21, 2012Filed: Aug 26, 2015Published: Jan 21, 2016
Est. expiryDec 21, 2032(~6.4 yrs left)· nominal 20-yr term from priority
C07H 19/207A61P 31/14C07H 19/16C07H 19/06C07H 19/10C07H 19/173C07H 19/213C07H 19/20A61K 31/7076A61P 31/20
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Claims

Abstract

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

Claims

exact text as granted — not AI-modified
1 . (canceled) 
     
     
         2 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure: 
       
         
           
           
               
               
           
         
         wherein: 
         B 1  is 
       
       
         
           
           
               
               
           
         
         R 1  is methyl or ethynyl; 
         R 2  is hydroxyl or fluoro; 
         R 3  is hydroxyl; 
         R 4  is hydrogen or 
       
       
         
           
           
               
               
           
         
         R 5A  is O − , OH, or an optionally substituted N-linked α-amino acid ester derivative; 
         R 5B  is O − , OH, an —O-optionally substituted aryl, or 
       
       
         
           
           
               
               
           
         
       
       where n is 0 or 1;
 R 6B  is H; 
 R 6C  is H or unsubstituted C 1-6  alkyl; 
 R 9 , R 10  and R 11  are independently absent or hydrogen; and 
 Z 1  is O or S. 
 
     
     
         3 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Z 1  is S. 
     
     
         4 . The compound of  claim 3 , or a pharmaceutically acceptable salt thereof, wherein B 1  is 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 6C  is H or methyl. 
     
     
         6 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1  is methyl. 
     
     
         7 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1  is ethynyl. 
     
     
         8 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2  is hydroxyl. 
     
     
         9 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2  is fluoro. 
     
     
         10 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 5A  is an optionally substituted N-linked a-amino acid ester derivative; and R 5B  is an —O-optionally substituted aryl. 
     
     
         11 . The compound of  claim 10 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted N-linked α-amino acid ester derivative is N-alaninyl isopropyl ester, N-alaninyl cyclohexyl ester, N-alaninyl neopentyl ester, N-valinyl isopropyl ester or N-leucinyl isopropyl ester. 
     
     
         12 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 5A  is O −  or OH; and R 5B  is O − , OH or 
       
         
           
           
               
               
           
         
       
     
     
         13 . The compound of  claim 12 , or a pharmaceutically acceptable salt thereof, wherein n is 1. 
     
     
         14 . The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein Z 1  is O. 
     
     
         15 . The compound of  claim 14 , or a pharmaceutically acceptable salt thereof, wherein B 1  is 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1  is methyl. 
     
     
         17 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1  is ethynyl. 
     
     
         18 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 2  is hydroxyl. 
     
     
         19 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 2  is fluoro. 
     
     
         20 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1  is methyl and R 2  is fluoro. 
     
     
         21 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 5A  is an optionally substituted N-linked a-amino acid ester derivative; and R 5B  is an —O-optionally substituted aryl. 
     
     
         22 . The compound of  claim 21 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted N-linked α-amino acid ester derivative is N-alaninyl isopropyl ester, N-alaninyl cyclohexyl ester, N-alaninyl neopentyl ester, N-valinyl isopropyl ester or N-leucinyl isopropyl ester. 
     
     
         23 . The compound of  claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 5A  is O −  or OH; and R 5B  is O − , OH or 
       
         
           
           
               
               
           
         
       
     
     
         24 . The compound of  claim 23 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

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