Antimicrobial compounds and methods of making and using the same

Abstract

The present disclosure relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals. In some embodiments, the present disclosure provides a compound of Formula (A) or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.

1 . A compound of Formula (A): 
       
         
           
           
               
               
           
         
         or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
 J is selected from 
 
       
       
         
           
           
               
               
           
         
         
           X is selected from a 5- or 6-membered heterocyclyl ring and phenyl, wherein each of the 5- or 6-membered heterocyclyl ring and phenyl is optionally substituted with one or more R X ; 
           R 1  is selected from H and C 1-3  alkyl; 
           R 2  is selected from H and C 1-3  alkyl; 
           R 3  is selected from H and C 1-3  alkyl; 
           Or R 2  and R 3  together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring; 
           R 4  is selected from H and C 1-3  alkyl; 
           R 5  is selected from H and C 1-6  alkyl; 
           R 6  is selected from H, C 1-6  alkyl, C 2-6  alkenyl, and C 3-6  cycloalkyl, wherein the C 1-6  alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, OR a , SR a , —C(O)OR a , —SC(NH)NH 2 , C 3-6  cycloalkyl, and 3-6 membered heterocyclyl; 
           R7 is selected from H and C 1-6  alkyl; 
           or R6 and R 7  together with the carbon and nitrogen atoms to which they are attached form a ring having one of the formulas: 
         
       
       
         
           
           
               
               
           
         
         
           wherein the ring is optionally substituted on a ring carbon atom with C 1-6  alkyl, wherein the C 1-6  alkyl is optionally substituted with one or more OH; 
           or R5 and R7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form a ring having one of the formulas: 
         
       
       
         
           
           
               
               
           
         
         
           R8 is selected from H and halogen; 
           each R X  is independently selected from halogen, C 1-6  alkyl, C 1-4  haloalkyl, OR c , N(R c ) 2 , —C(O)OR c , —C(O)R c , C 3-6  cycloalkyl, and aryl, wherein the C 1-6  alkyl is optionally substituted with one or more R b ; 
           or two adjacent R X  come together with the atoms to which they are attached to form a 5- or 6-membered ring; 
           each R a  is independently selected from H and C 1-6  alkyl; 
           each R b  is independently selected from C 2-6  alkenyl, OR c , N(R c ) 2 , —C(O)OR c , C 3-6  cycloalkyl, OC(NH)NH 2 , and aryl; 
           each R c  is independently selected from H, C 1-6  alkyl, aryl, —C(O)aryl, and —(CH 2 )aryl, wherein the C 1-6  alkyl and the aryl are each optionally substituted with one or more R d ; and 
           each R d  is independently selected from C 1-3  alkyl, OH, O(C 1-3  alkyl), NO 2 , NH 2 , NH(C 1-3  alkyl), and N(C 1-3  alkyl) 2 ; or a compound of formula (I): 
         
       
       
         
           
           
               
               
           
         
         
           or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein: 
           X is selected from a 5- or 6-membered heterocyclyl ring and phenyl, wherein each of the 5- or 6-membered heterocyclyl ring and phenyl is optionally substituted with one or more R X . 
           R 1  is selected from H and C 1-3  alkyl; 
           R 2  is selected from H and C 1-3  alkyl; 
           R 3  is selected from H and C 1-3  alkyl; 
           Or R 2  and R 3  together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring; 
           R 4  is selected from H and C 1-3  alkyl; 
           R 5  is selected from H and C 1-6  alkyl; 
           R 6  is selected from H, C 1-6  alkyl, C 2-6  alkenyl, and C 3-6  cycloalkyl, wherein the C 1-6  alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, OR a , SR a , —C(O)OR a , —SC(NH)NH 2 , C 3-6  cycloalkyl, and 3-6 membered heterocyclyl; 
           R7 is selected from H and C 1-6  alkyl; 
           or R6 and R 7  together with the carbon and nitrogen atoms to which they are attached form a ring having one of the formulas: 
         
       
       
         
           
           
               
               
           
         
         
           wherein the ring is optionally substituted on a ring carbon atom with C 1-6  alkyl, wherein the C 1-6  alkyl is optionally substituted with one or more OH; 
           or R5 and R 7  together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form a ring having one of the formulas: 
         
       
       
         
           
           
               
               
           
         
         
           R8 is selected from H and halogen; 
           each R X  is independently selected from halogen, C 1-6  alkyl, C 1-4  haloalkyl, OR c , N(R c ) 2 , —C(O)OR c , —C(O)R c , C 3-6  cycloalkyl, and aryl, wherein the C 1-6  alkyl is optionally substituted with one or more R b ; 
           or two adjacent R X  come together with the atoms to which they are attached to form a 5- or 6-membered ring; 
           each R a  is independently selected from H and C 1-6  alkyl; 
           each R b  is independently selected from C 2-6  alkenyl, OR c , N(R c ) 2 , —C(O)OR c , C 3-6  cycloalkyl, OC(NH)NH 2 , and aryl; 
           each R c  is independently selected from H, C 1-6  alkyl, aryl, —C(O)aryl, and —(CH 2 )aryl, wherein the C 1-6  alkyl and the aryl are each optionally substituted with one or more R d ; and 
           each R d  is independently selected from C 1-3  alkyl, OH, O(C 1-3  alkyl), NO 2 , NH 2 , NH(C 1-3  alkyl), and N(C 1-3  alkyl) 2 . 
         
       
     
     
         2 . The compound of  claim 1 , wherein each of R 1 , R 2 , and R 3  is H. 
     
     
         3 . The compound of  claim 1 , wherein two of R 1 , R 2 , and R 3  are H, and the other is C 1-3  alkyl. 
     
     
         4 . The compound of  claim 1 , wherein two of R 1 , R 2 , and R 3  are H, and the other is methyl. 
     
     
         5 . The compound of  claim 1 , wherein one of R 1 , R 2 , and R 3  is H, and the other two are C 1-3  alkyl. 
     
     
         6 . The compound of  claim 1 , wherein one of R 1  R 2 , and R 3  is H, and the other two are methyl. 
     
     
         7 . The compound of  claim 1 , wherein R 1  is H; and R 2 , and R 3  together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring. 
     
     
         8 . The compound of  claim 1 , wherein R 1  is H; and R 2  and R 3  together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form an imidazoline. 
     
     
         9 . The compound of  claim 1 , wherein R 4  is H. 
     
     
         10 . The compound of  claim 1 , wherein R 4  is C 1-3  alkyl. 
     
     
         11 . The compound of  claim 1 , wherein one of R 5  and R 7  is H and the other is C 1-6  alkyl. 
     
     
         12 . The compound of  claim 1 , wherein R 5  is H and R 7  is C 1-6  alkyl. 
     
     
         13 . The compound of  claim 1 , wherein R 5  and R 7  together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 1 , wherein R 5  and R 7  together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form 
       
         
           
           
               
               
           
         
       
       wherein the ring is optionally substituted with C 1-6  alkyl, wherein the C 1-6  alkyl is optionally substituted with one or more OH. 
     
     
         15 . The compound of  claim 1 , wherein R 5  and R 7  together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 1 , wherein R 5  and R 7  together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 1 , wherein R 6  and R 7  together with the carbon and nitrogen atoms to which they are attached form a ring of formula 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 1 , wherein R 6  and R 7  together with the carbon and nitrogen atoms to which they are attached form a ring of formula 
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound of  claim 1 , wherein R 6  is selected from H and C 1-6  alkyl optionally substituted with one or more substituents selected from the group consisting of halogen and OR a . 
     
     
         20 .- 27 . (canceled) 
     
     
         28 . The compound of  claim 1 , wherein X is selected from a 5-membered heterocyclyl ring and phenyl, wherein each of the 5-membered heterocyclyl ring and phenyl is optionally substituted with one or more R X . 
     
     
         29 .- 344 . (canceled)