US2020140425A1PendingUtilityA1

Compounds for the treatment of tuberculosis

Assignee: BROAD INST INCPriority: Mar 13, 2013Filed: Apr 10, 2019Published: May 7, 2020
Est. expiryMar 13, 2033(~6.6 yrs left)· nominal 20-yr term from priority
C07D 417/12C07D 413/04C07D 285/125C07D 413/14C07D 263/46C07D 413/12C07D 417/04C07D 271/10C07D 271/113A61P 31/06
57
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Claims

Abstract

Disclosed are compounds that can be used for treating tuberculosis.

Claims

exact text as granted — not AI-modified
1 - 24 . (canceled) 
     
     
         25 . A compound of Formula I or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         A 1 , is O; 
         A 2  is N; 
         R 1  is S, N, O, optionally substituted C 1 -C 6  linear or branched alkyl, or sulfonyl, as valence and stability permit; 
         R 2  is null or optionally substituted linear or branched C 1 -C 12  alkyl; 
         R 3  is null, O, H, optionally substituted C 1 -C 6  linear or branched alkyl, or 
       
       
         
           
           
               
               
           
         
       
       as valence and stability permit;
 R 4  is H, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocycle, optionally substituted C 1 -C 6  alkoxy, or an optionally substituted amide; 
 R 5  is an optionally substituted heteroaryl, optionally substituted C 4 -C 6  carbocycle, or optionally substituted C 1 -C 6  linear or branched alkyl. 
 
     
     
         26 . The compound of  claim 25  or a pharmaceutically acceptable salt thereof, wherein R 4  is H, 
       
         
           
           
               
               
           
         
         optionally substituted C 1 -C 6  alkoxy, or optionally substituted alkylamino, 
       
       wherein
 R 7  is H, 
 
       
         
           
           
               
               
           
         
       
       halo, cyano, C 1 -C 6  alkoxy, linear or branched alkyl, haloalkyl, optionally substituted aryl; optionally substituted arylalkyl, halogen substituted C 1 -C 6  alkoxy; and
 R 8  and R 9  are independently H, OH, halo, or C 1 -C 6  alkyl. 
 
     
     
         27 . The compound of  claim 25  or or a pharmaceutically acceptable salt thereof, wherein R 5  is C 1 -C 6  linear or branched alkyl, 
       
         
           
           
               
               
           
         
       
       wherein
 R 6  is H, halo, optionally substituted aryl, C 1 -C 6  linear or branched alkyl, C 1 -C 6  alkoxy, haloalkyl, halogen substituted C 1 -C 6  alkoxy, cyano, or 
 
       
         
           
           
               
               
           
         
       
     
     
         28 - 30 . (canceled) 
     
     
         31 . The compound of  claim 25  or a pharmaceutically acceptable salt thereof, wherein R 3  is null. 
     
     
         32 . The compound of  claim 25  or a pharmaceutically acceptable salt thereof, wherein R 2  is null or C 1 -C 12  alkyl. 
     
     
         33 . The compound of  claim 25  or a pharmaceutically acceptable salt thereof, wherein
 R 1  is S; and 
 R 3  is null. 
 
     
     
         34 . (canceled) 
     
     
         35 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof wherein R 5  is C 1 -C 6  linear or branched alkyl, 
       
         
           
           
               
               
           
         
         wherein 
       
       R 6  is H, halo, optionally substituted aryl, C 1 -C 6  linear or branched alkyl, C 1 -C 6  alkoxy, haloalkyl, halogen substituted C 1 -C 6  alkoxy, cyano, or 
       
         
           
           
               
               
           
         
       
     
     
         36 . The compound of  claim 35 , or a pharmaceutically acceptable salt thereof wherein R 5  is: 
       
         
           
           
               
               
           
         
       
       wherein
 R 6  is H, halo, C 1 -C 6  linear or branched alkyl, C 1 -C 6  haloalkyl, cyano, C 1 -C 6  alkoxy, halogen substituted C 1 -C 6  alkoxy, OH, —O(CH 2 ) q C(═O)O(CH 2 ) p CH 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) q C≡CH, or 
 
       
         
           
           
               
               
           
         
         wherein m, p and q are independently 1-4. 
       
     
     
         37 . (canceled) 
     
     
         38 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof wherein R 6  is H, halo, methyl, ethyl, or propyl, CF 3 , cyano, OH, —O(CH 2 ) q C(═O)O(CH 2 ) p CH 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , or —O(CH 2 ) q C≡CH. 
     
     
         39 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof wherein R 6  is H, methyl, ethyl, or propyl, CF 3 , halo, C 1 -C 6  alkoxy, OH, —O(CH 2 ) q C(═O)O(CH 2 ) p CH 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , or —O(CH 2 ) q C≡CH. 
     
     
         40 . The compound of  claim 36 , or a pharmaceutically acceptable salt thereof wherein R 6  is halo. 
     
     
         41 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof wherein R 1  is S or sulfonyl. 
     
     
         42 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof wherein R 1  is N. 
     
     
         43 . The compound of claim  1 , or a pharmaceutically acceptable salt thereof wherein R 1  is optionally substituted C 1 -C 6  linear or branched alkyl. 
     
     
         44 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof wherein:
 R 1  is S;   R 2  null or optionally substituted linear or branched C 1 -C 12  alkyl;   R 3  is null or O; and   R 4  is H, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocycle, optionally substituted C 1 -C 6  alkoxy, or an optionally substituted amide.   
     
     
         45 . The compound of  claim 44 , or a pharmaceutically acceptable salt thereof wherein:
 R 4  is H, —C≡CH, —C≡C(CH 2 ) t OH, —C(═O)O(CH 2 ) t CH 3 , —O(CH 2 ) u CH 3 , —O(CH 2 ) q C(═O)O(CH 2 ) p CH 3     
       
         
           
           
               
               
           
         
       
       optionally substituted C 1 -C 6  alkoxy, optionally substituted alkylamino, or C 1 -C 6  carbocycle, wherein
 R 7  is H, O, 
 
       
         
           
           
               
               
           
         
       
       halo, cyano, —C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) m N 3 , —O(CH 2 ) m C≡CH, C 1 -C 6  alkoxy, optionally substituted C 1 -C 6  linear or branched alkyl, haloalkyl, optionally substituted aryl; optionally substituted arylalkyl, or halogen substituted C 1 -C 6  alkoxy; and
 R 8  and R 9  are independently H, OH, ═O, halo, or C 1 -C 6  alkyl. 
 m, p and q are independently 1-6; and 
 t and u are independently 0-6. 
 
     
     
         46 . The compound of  claim 25  or a pharmaceutically acceptable salt thereof, wherein the compound has the Formula I-b, I-c, I-d, or I-e: 
       
         
           
           
               
               
           
         
       
       wherein
 R 4  is H, —C≡CH, —C≡C(CH 2 ) t OH, —C(═O)O(CH 2 ) t CH 3 , —O(CH 2 ) u CH 3 , —O(CH 2 ) q C(═O)(O)CH 2 ) p CH 3 , 
 
       
         
           
           
               
               
           
         
       
       optionally substituted C 1 -C 6  alkoxy, optionally substituted alkylamino, or C 1 -C 6  carbocycle,
 R 7  is H, O, 
 
       
         
           
           
               
               
           
         
       
       halo, cyano, —C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) m N 3 , —O(CH 2 ) m C≡CH, C 1 -C 6  alkoxy, optionally substituted C 1 -C 6  linear or branched alkyl, haloalkyl, optionally substituted aryl; optionally substituted arylalkyl, or halogen substituted C 1 -C 6  alkoxy; and
 R 8  and R 9  are independently H, OH, ═O, halo, or C 1 -C 6  alkyl; 
 R 5  is 
 
       
         
           
           
               
               
           
         
         R 6  is H, halo, C 1 -C 6  linear or branched alkyl, C 1 -C 6  haloalkyl, cyano, C 1 -C 6  alkoxy, halogen substituted C 1 -C 6  alkoxy, OH, —O(CH 2 ) q C(═O)O(CH 2 ) p CH 3 , —O(CH 2 ) q C(═O)N(H)(CH 2 ) p O(CH 2 ) m N 3 , —O(CH 2 ) q C≡CH, or 
       
       
         
           
           
               
               
           
         
         wherein m, p, q, and z are independently 1-6; 
         t and u are independently 0-6. 
       
     
     
         47 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         48 . The compound of  claim 25 , or a pharmaceutically acceptable salt thereof, provided that the compound is not selected from: 
     
     
         49 - 55 . (canceled)

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