US2020181142A1PendingUtilityA1

Derivatives And Methods Of Treating Hepatitis B Infections

77
Assignee: NOVIRA THERAPEUTICS INCPriority: Dec 30, 2014Filed: Dec 3, 2019Published: Jun 11, 2020
Est. expiryDec 30, 2034(~8.5 yrs left)· nominal 20-yr term from priority
C07D 471/04A61K 45/06C12N 2730/10134A61K 31/437C12N 2730/10111A61K 31/501A61K 39/292A61K 38/212C12N 7/00A61K 31/5377A61P 31/12A61K 31/4375C12N 2730/10171A61K 31/4545
77
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Claims

Abstract

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

Claims

exact text as granted — not AI-modified
1 . A compound of Formula II 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         Y is selected from —C(O)— and —SO 2 —; 
         Z is selected from —(CR 5 R 6 ) m —, —(CR 5 R 6 ) m O—, and —(CR 5 R 6 ) m —NR′—; 
         R 1  is selected from C 6 -C 12 -aryl and C 1 -C 9 -heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 or 2 groups each independently selected from —OH, halo, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —O—C 1 -C 6 -alkyl, and C 1 -C 6 -alkyl-OH; 
         R 2  is, at each occurrence, independently selected from H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —O—C 1 -C 6 -alkyl, and C 1 -C 6 -alkyl-OH; 
         R 3  is H, 
         R 4  is selected from C 1 -C 6 -alkyl, (CR 8 R 9 ) p —C 3 -C 8 -cycloalkyl, (CR 8 R 9 ) p —C 2 -C 8 -heterocyclyl, (CR 8 R 9 ) p —C 6 -C 12 -aryl, and (CR 8 R 9 ) p —C 1 -C 9 -heteroaryl, wherein alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1 or 2 groups, each independently selected from —OH, halo, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, —O—C 1 -C 6 -alkyl, C(O)N(R f ) 2 , C(O)OR f , —OCH 2 C(O)OR f , —SO 2 R f , and C 1 -C 6 -alkyl-OH; 
         R 5  is, at each occurrence H, 
         R 6  is, at each occurrence, H, 
         R 7  is selected from H, C 1 -C 6 -alkyl, and C 1 -C 6 -alkyl-OH; 
         R 8  is, at each occurrence, independently selected from H and C 1 -C 6 -alkyl; 
         R 9  is, at each occurrence, H, 
         R a  H; 
         R f  is, at each occurrence, independently selected from H and C 1 -C 6 -alkyl; 
         m is 0, 1, or 2; 
         n is 1; and 
         p is 0 or 1. 
       
     
     
         2 - 6 . (canceled) 
     
     
         7 . The compound of  claim 1 , wherein
 m is 0 or 1; and   R 7  is H or C 1 -C 6 -alkyl.   
     
     
         8 . The compound of  claim 1 , wherein R 1  is C 6- aryl optionally substituted with halo. 
     
     
         9 . (canceled) 
     
     
         10 . The compound of  claim 1 , wherein R 2  is H. 
     
     
         11 . The compound of 1, wherein R 4  is (CR 8 R 9 ) p —C 3 -C 8 -cycloalkyl, (CR 8 R 9 ) p —C 2 -C 8 -heterocyclyl, (CR 8 R 9 ) p —C 6 -C 12 -aryl, or (CR 8 R 9 ) p —C 1 -C 9 -heteroaryl, wherein cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1 or 2 groups, each independently selected from —OH, halo, CN, C 1 -C 6 -haloalkyl, —O—C 1 -C 6 -alkyl, C(O)N(R f ) 2 , C(O)OR f , —OCH 2 C(O)OR f , —SO 2 R f , and C 1 -C 6 -alkyl-OH. 
     
     
         12 . The compound of  claim 1 , wherein R 4  is (CR 8 R 9 ) p —C 6 -C 12 -aryl or (CR 8 R 9 ) p —C 1 -C 6 -heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 or 2 groups, each independently selected from —OH, halo, CN, C 1 -C 6 -alkyl, C 1 —O 6 -haloalkyl, C(O)N(R f ) 2 , C(O)OR f , —OCH 2 C(O)OR f , —SO 2 R f , and C 1 -C 6 -alkyl-OH. 
     
     
         13 . The compound of  claim 1 , wherein
 p is 0 or 1.   
     
     
         14 . (canceled) 
     
     
         15 . The compound of  claim 1 , wherein
 Y is —C(O)—;   Z is NR 7 ; and   R 7  is H or C 1-4 -alkyl.   
     
     
         16 - 41 . (canceled) 
     
     
         42 . The compound of  claim 1 , wherein the compound is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         43 - 54 . (canceled) 
     
     
         55 . The compound of  claim 1 , wherein R 4  is (CR 8 R 9 ) p —C 6 -C 12 -aryl, or (CR 8 R 9 ) p —C 1 -C 9 -heteroaryl, and wherein aryl and heteroaryl are optionally substituted with 1 or 2 groups, each independently selected from —OH, halo, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, alkyl, and C 1 -C 6 -alkyl-OH. 
     
     
         56 . The compound of  claim 1 , wherein the compound of Formula II is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.

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