Analogs of Nitrofuran Antibiotics to Combat Resistance

Abstract

Novel compounds and methods of killing or inhibiting the growth of bacteria.

What is claimed is: 
     
         1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is C 6 -C 10  aryl, biaryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C 6 -C 10  aryl, biaryl, or mono- or bicyclic heteroaryl is optionally substituted with halogen, —OR 5 , —NR 5 R 6 , —S(O) 2 NR 5 R 6 , or —N(R 5 )SO 2 R 6 ; 
         R 2  is hydrogen; 
         or R 1  and R 2  combine with the atoms to which they are attached to form a 3- to 7-membered heterocycloalkyl optionally substituted by oxo; 
         R 3  is C 6 -C 10  aryl, biaryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C 6 -C 10  aryl aryl, biaryl, and mono- or bicyclic heteroaryl is optionally substituted by —OR 5  or nitro; 
         R 4  is hydrogen; 
         R 5  and R 6  are each individually hydrogen, C 1 -C 6  alkyl, C 6 -C 10  aryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C 1 -C 6  alkyl, C 6 -C 10  aryl, and mono- or bicyclic heteroaryl is optionally substituted with halogen or —OC 1 -C 6  alkyl; 
         or a pharmaceutically acceptable salt thereof, 
         provided the compound is not 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is mono- or bicyclic heteroaryl optionally substituted by nitro. 
     
     
         3 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is quinolyl optionally substituted by —OR 5 . 
     
     
         4 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is napthyl optionally substituted by —OR 5 . 
     
     
         5 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3  is furanyl optionally substituted by nitro. 
     
     
         6 . The compound of  claim 1 , having the formula (II) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . The compound of  claim 1 , having the formula (III) 
       
         
           
           
               
               
           
         
         wherein Z is CH or N; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         8 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is monocylic heteroaryl optionally substituted with halogen. 
     
     
         9 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is C 6 -C 10  aryl optionally substituted with halo, —OR 5 , —NR 5 R 6 , —S(O) 2 NR 5 R 6 , or —N(R 5 )SO 2 R 6 . 
     
     
         10 . The compound of  claim 7 , wherein R 1  is C 6 -C 10  aryl optionally substituted by —OH, —OC 1 -C 6  alkyl, O-aryl, —N(C 1 -C 6  alkyl) 2 , —S(O) 2 N(C 1 -C 6  alkyl) 2 , —N(H)S(O) 2 —C 6 -C 10  aryl, —N(H)S(O) 2 -monocylic heteroaryl, or —N(H)S(O) 2 -bicylic heteroaryl, wherein each hydrogen atom in C 6 -C 10  aryl, or mono- or bicyclic heteroaryl is optionally substituted with halogen or —OC 1 -C 6  alkyl. 
     
     
         11 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1  is biaryl. 
     
     
         12 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         13 . The compound, of  claim 10 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 11 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claim 10 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 13 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         17 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and optionally at least one diluent, carrier or excipient. 
     
     
         18 . A method of treating a bacterial infection comprising administering to a subject in need of such treatment an effective amount of at least one compound of  claim 1 , or a pharmaceutically acceptable salt thereof.