US2020392105A1PendingUtilityA1

Acyl Sulfonamides that are BCL Family Antagonists for Use in Clinical Management of Conditions Caused or Mediated by Senescent Cells and for Treating Cancer

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Assignee: UNITY BIOTECHNOLOGY INCPriority: Jun 13, 2018Filed: May 29, 2020Published: Dec 17, 2020
Est. expiryJun 13, 2038(~11.9 yrs left)· nominal 20-yr term from priority
C07D 401/10C07D 403/10A61P 35/00A61P 27/00C07D 401/14A61P 9/10
61
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Claims

Abstract

The aryl sulfonamide compounds of this invention have powerful and cell-type specific Bcl inhibitory activity. Selected compounds in this class promote apoptosis in senescent cells, and are being developed for treating senescent-related conditions. Selected compounds in this class promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

Claims

exact text as granted — not AI-modified
1 . A compound according to formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 X 1  is —Cl; 
 X 2  is —COOH; 
 X 3  is —SO 2 CF 3 ; —SO 2 CH 3 ; or —NO 2    
 X 5  is —F or —H; 
 R 1  is —CH(CH 3 ) 2 ; 
 R 2  is —CH 3 ; 
 R 3  and R 4  are both —H; 
 n 1  is 2; and 
 R 6  is selected from —OH, 
 
       
       
         
           
           
               
               
           
         
         wherein the hydroxyl group in R 6  is optionally phosphorylated, 
         with the proviso that if X 3  is —SO 2 CF 3 , then the hydroxyl group in R 6  must be phosphorylated. 
       
     
     
         2 .- 20 . (canceled) 
     
     
         21 . A method of eliminating senescent cells from a mixed cell population or tissue, comprising contacting the cell population or tissue with a compound according to Formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 X 1  is —Cl; 
 X 2  is —COOH; 
 X 3  is —SO 2 CF 3 ; —SO 2 CH 3 ; or —NO 2    
 X 5  is —F or —H; 
 R 1  is —CH(CH 3 ) 2 ; 
 R 2  is —CH 3 ; 
 R 3  and R 4  are both —H; 
 n 1  is 2; and 
 R 6  is selected from —OH, 
 
       
       
         
           
           
               
               
           
         
         wherein the hydroxyl group in R 6  is optionally phosphorylated. 
       
     
     
         22 . The method of  claim 21 , wherein X 3  is —SO 2 CF 3 . 
     
     
         23 . The method of  claim 21 , wherein X 3  is —SO 2 CH 3 . 
     
     
         24 . The method of  claim 21 , wherein X 3  is —NO 2    
     
     
         25 . The method of  claim 21 , wherein X 5  is —F. 
     
     
         26 . The method of  claim 21 , wherein X 5  is —H. 
     
     
         27 . The method of  claim 21 , wherein R 6  is —OH. 
     
     
         28 . The method of  claim 21 , wherein R 6  is 
       
         
           
           
               
               
           
         
       
     
     
         29 . The method of  claim 21 , wherein R 6  is 
       
         
           
           
               
               
           
         
       
     
     
         30 . The method of  claim 21 , wherein the hydroxyl group in R 6  is phosphorylated. 
     
     
         31 . The method of  claim 21 , wherein if X 3  is —SO 2 CF 3 , then the hydroxyl group in R 6  is phosphorylated. 
     
     
         32 . The method of  claim 21 , wherein the hydroxyl group in R 6  is phosphorylated with —PO 3 H 2 . 
     
     
         33 . The method of  claim 21 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         34 . The method of  claim 21 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         35 . The method of  claim 21 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         36 . The method of  claim 21 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         37 . The method of  claim 21 , wherein the compound is:

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