N-sulfonyl-4-methyleneamino-3-hydroxy-2-pyridones

Abstract

Compounds of Formula (I): are effective in the treatment of a microbial infection.

1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       wherein: 
 a. R 1  is aryl, optionally substituted with one or more hydrogen, halo, cyano, hydroxy, carboxy, keto, thioketo, amino, acylamino, acyl, amido, phenyl, aryloxy, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, alkoxy, aryl, cycloalkyl, spirocycloalkyl or combinations thereof;  
 b. each R 2  is independently chosen from hydrogen, halo, cyano, hydroxy, carboxy, keto, thioketo, amino, acylamino, acyl, amido, phenyl, aryloxy, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, alkoxy, aryl, and cycloalkyl;  
 c. R 3  and R 4 , together with the nitrogen atom to which they are bonded, join to form heterocycloalkyl moieties, optionally substituted with one or more hydrogen, halo, cyano, hydroxy, carboxy, keto, thioketo, amino, acylamino, acyl, amido, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, heterocycloalkyl, spirocycloalkyl, and combinations thereof; and  
 d. R 5  and R 6  are each independently chosen from hydrogen, halo, cyano, hydroxy, carboxy, keto, thioketo, amino, acylamino, acyl, amido, phenyl, aryloxy, alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, alkoxy, aryl, and cycloalkyl; or  
 optical isomers, diastereomers and enantiomers of the formula above, or a pharmaceutically-acceptable salt thereof.  
 
     
     
         2 . The compound of  claim 1 , wherein R 1  is substituted or unsubstituted phenyl.  
     
     
         3 . The compound of  claim 2 , wherein the phenyl group of R 1  is substituted with an alkyl.  
     
     
         4 . The compound of  claim 1 , wherein R 1  is aryl substituted with a heteroalkyl.  
     
     
         5 . The compound of  claim 1 , wherein R 1  is aryl substituted with an aryl.  
     
     
         6 . The compound of  claim 1 , wherein R 1 , R 2 , R 5 , and R 6 , are hydrogen.  
     
     
         7 . The compound of  claim 1 , wherein R 1  is phenyl, substituted with methyl.  
     
     
         8 . The compound of  claim 1 , wherein R 2  is hydrogen.  
     
     
         9 . The compound of  claim 1 , wherein R 3  and R 4  join to form a heteroaryl.  
     
     
         10 . The compound of  claim 1 , wherein R 3  and R 4  join to form a heterocycloalkyl.  
     
     
         11 . The compound of  claim 9 , wherein the heteroaryl formed by joining of R 3  and R 4  is further substituted with a heteroaryl.  
     
     
         12 . The compound of  claim 9 , wherein the heteroaryl formed by joining of R 3  and R 4  is further substituted with a heterocycloalkyl.  
     
     
         13 . The compound of  claim 10 , wherein the heterocycloalkyl formed by joining of R 3  and R 4  is further substituted with a heteroaryl.  
     
     
         14 . The compound of  claim 10 , wherein the heterocycloalkyl formed by joining of R 3  and R 4  is further substituted with a heterocycloalkyl.  
     
     
         15 . The compound of  claim 1 , wherein R 5  and R 6  are hydrogen.  
     
     
         16 . The compound of  claim 1 , selected from the group consisting of: 
 3-Hydroxy-4-pyrrolidin-1-ylmethyl-1-(toluene-4-sulfonyl)-1H-pyridin-2-one;    3-Hydroxy-4-thiazolidin-3-ylmethyl-1-(toluene-4-sulfonyl)-1H-pyridin-2-one;    4-Azocan-1ylmethyl-3-hydroxy-1-(toluene-4-sulfonyl)-1H-pyridin-2-one; and    4-[1,4′]Bipiperidinyl-1′-ylmethyl-3-hydroxy-1-(toluene-4-sulfonyl)-1H-pyridin-2-one.    
     
     
         17 . A method of treating a microbial infection comprising administering a safe and effective of amount of a compound according to  claim 1 , in a subject in need thereof.  
     
     
         18 . A method of treating a microbial infection comprising administering a safe and effective of amount of a compound according to  claim 16 , in a subject in need thereof.  
     
     
         19 . A pharmaceutical composition comprising: 
 a. a safe and effective of amount of a compound according to  claim 1;     b. a pharmaceutically-acceptable excipient.    
     
     
         20 . A pharmaceutical composition comprising: 
 a. a safe and effective of amount of a compound according to  claim 16;     b. a pharmaceutically-acceptable excipient.