US2023391734A1PendingUtilityA1

Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

Assignee: NEUROPORE THERAPIES INCPriority: Oct 30, 2017Filed: Jun 5, 2023Published: Dec 7, 2023
Est. expiryOct 30, 2037(~11.3 yrs left)· nominal 20-yr term from priority
C07D 249/12A61P 25/28A61K 9/10A61P 3/00C07D 243/10A61K 31/18A61P 25/00A61K 31/4196A61K 31/5377A61K 31/454A61K 31/496A61K 47/36A61K 47/38A61K 47/32C07D 401/10C07D 403/10
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Claims

Abstract

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

Claims

exact text as granted — not AI-modified
1 - 23 . (canceled) 
     
     
         24 . A pharmaceutical composition comprising a at least one compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2 , and R 3  are each independently hydrogen, hydroxy, halogen, optionally substituted C 1-4  alkyl, optionally substituted C 1-4  alkoxy, —CN, —C(O)R x , —C(O)OR x , —S(O) 2 R x , or —NR y R z ; 
         R x , R y , and R z  are each independently H or optionally substituted C 1-4 alkyl, or R y  and R z  taken together with the nitrogen to which they are attached form an optionally substituted monocyclic heterocycloalkyl ring; 
         or a pharmaceutically acceptable salt thereof, and 
         (b) HPMC-AS. 
       
     
     
         25 . (canceled) 
     
     
         26 . The pharmaceutical composition of  claim 24 , wherein the pharmaceutical composition is in the form of a spray dry dispersion (SDD). 
     
     
         27 - 30 . (canceled) 
     
     
         31 . The pharmaceutical composition of  claim 24 , wherein R 1  is hydrogen. 
     
     
         32 . The pharmaceutical composition of  claim 24 , wherein R 1  is —OCH 2 CH 2 —O—CH 2 CH 3  or —OCH 2 CH 2 OCH 3 . 
     
     
         33 . The pharmaceutical composition of  claim 24 , wherein R 1  is —NHCH 2 CH 2 OH or —N(CH 2 CH 3 ) 2 . 
     
     
         34 . The pharmaceutical composition of  claim 24 , wherein R 1  is morpholinyl, 4-methyl-piperazin-1-yl, piperidinyl, or pyrrolidinyl. 
     
     
         35 . The pharmaceutical composition of  claim 24 , wherein R 2  is hydrogen, C 1-4  alkyl, or substituted C 1-4  alkyl. 
     
     
         36 . The pharmaceutical composition of  claim 24 , wherein R 2  is CF 3 . 
     
     
         37 . The pharmaceutical composition of  claim 24 , wherein R 2  is methyl. 
     
     
         38 . The pharmaceutical composition of  claim 24 , wherein R 2  is optionally substituted C 1-4  alkoxy, —CN, or —NR y R z . 
     
     
         39 . The pharmaceutical composition of  claim 24 , wherein R 2  is —N(CH 3 ) 2 . 
     
     
         40 . The pharmaceutical composition of  claim 24 , wherein R 2  is morpholinyl. 
     
     
         41 . The pharmaceutical composition of  claim 24 , wherein R 2  is methoxy, —OCH 2 CH 2 —O—CH 2 CH 3 , or —OCH 2 CH 2 OCH 3 . 
     
     
         42 . The pharmaceutical composition of  claim 24 , wherein R 3  is halogen. 
     
     
         43 . The pharmaceutical composition of  claim 24 , wherein R 3  is chloro. 
     
     
         44 . The pharmaceutical composition of  claim 24 , wherein R 3  is hydrogen. 
     
     
         45 . The pharmaceutical composition of  claim 24 , wherein R 3  is methyl. 
     
     
         46 . The pharmaceutical composition of  claim 24 , wherein R 3  is —CN. 
     
     
         47 . The pharmaceutical composition of  claim 24 , wherein R 3  is morpholinyl. 
     
     
         48 . The pharmaceutical composition of  claim 24 , wherein R 3  is C 1-4  alkoxy. 
     
     
         49 . The pharmaceutical composition of  claim 24 , wherein the compound is selected from the group consisting of 
       
         
           
                 
                 
                 
               
                     
                 
                   Compound 
                     
                     
                 
                   No. 
                   Structure 
                   Name 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   1 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- morpholinophenyl)-2,4-dihydro-3H-1,2,4- triazole-3-thione; 
                 
                     
                 
                   3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-(phenylsulfonyl)phenyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   4 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chlorophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   5 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- methylphenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   6 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-((4-(5-thioxo-1,5-dihydro-4H-1,2,4- triazol-4-yl)phenyl)sulfonyl)benzonitrile; 
                 
                     
                 
                   7 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4- morpholinophenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   8 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-methoxyphenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   9 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-tosylphenyl)-2,4-dihydro-3H-1,2,4- triazole-3-thione; 
                 
                     
                 
                   10 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-fluorophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   11 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   12 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3-methoxyphenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   13 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3-(2- ethoxyethoxy)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   14 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   3-((4-(5-thioxo-1,5-dihydro-4H-1,2,4- triazol-4-yl)phenyl)sulfonyl)benzonitrile; 
                 
                     
                 
                   15 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3- (dimethylamino)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   16 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3- morpholinophenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   17 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-(m-tolylsulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   18 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-((2- hydroxyethyl)amino)phenyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   19 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (piperidin-1-yl)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione; 
                 
                     
                 
                   20 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-(4- methylpiperazin-1-yl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   21 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (diethylamino)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione; 
                 
                     
                 
                   22 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-(2- ethoxyethoxy)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione; 
                 
                     
                 
                   23 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-methyl-3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione; 
                 
                     
                 
                   24 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (pyrrolidin-1-yl)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione; and 
                 
                     
                 
                   25 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   4-(4-((3-(2- methoxyethoxy)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione, 
                 
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         50 . The pharmaceutical composition of  claim 24 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         51 . The pharmaceutical composition of  claim 24 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.

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