Riminophenazines with 2-(heteroaryl) amino substituents and their anti-microbial activity

Abstract

The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments. A general representation of the 2-(heteroaryl)amino-riminophenazines is shown below.

1 . A compound having a structure of: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is a substituent selected from the group consisting of H, alkyl, alkoxy, monoalkylamino, dialkylamino, heterocycloalkyl containing at least one nitrogen atom, halo, CF 3 , OCF 3 , SCH 3 , SOCH 3 , and combinations of any two or three thereof, wherein the two or three substituents are the same; 
         R 2  is a substituent selected from the group consisting of alkyl, and cycloalkyl; 
         R 3  is a substituent selected from the group consisting of H, alkyl, alkoxy, monoalkylamino, dialkyl amino, heterocycloalkyl containing at least one nitrogen atom, halo, NHCOCH 3 , and combinations of any two or three thereof, wherein the two or three substituents are the same or different; 
         R 4  is a substituent selected from the group consisting of H, alkyl, alkoxy, halo, or monoalkylamino, dialkylamino, and heterocycloalkyl containing at least one nitrogen atom; 
         X is N; 
         Y is CH or N; and 
         Z is CH or N. 
       
     
     
         2 . (canceled) 
     
     
         3 . The compound of  claim 1 , wherein one or more of R 1 , R 3 , and R 4  are heterocycloalkyl containing at least one nitrogen atom and wherein the heterocycloalkyl further comprises one or more additional heteroatoms selected from the group consisting of O, S or NR′, wherein R′ is an alkyl group. 
     
     
         4 . (canceled) 
     
     
         5 . The compound of  claim 1 , wherein R 2  is cycloalkyl and wherein the cycloalkyl further comprises O, S, or NR′, wherein R′ is an alkyl group. 
     
     
         6 . (canceled) 
     
     
         7 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer or stabilizer. 
     
     
         8 . (canceled) 
     
     
         9 . The pharmaceutical composition of  claim 7 , further comprising one or more additional anti-infective treatments. 
     
     
         10 . A method of preventing and treating microbial infection comprising administering the pharmaceutical composition of  claim 7 . 
     
     
         11 . The method of  claim 10 , wherein the microbial infection is caused by  Mycobacterium tuberculosis.    
     
     
         12 - 26 . (canceled)