Pyrazinoic acid conjugates and hybrid conjugates

Abstract

Pyrazinamide (PZA) conjugates and hybrids are provided herein. The PZA conjugates are useful for treating bacterial infections. In one embodiment, the PZA conjugates are useful for treating tuberculosis.

We claim: 
     
         1 . A pyrazinamide conjugate, consisting of 
       
         
           
           
               
               
           
         
       
       or an isolated optical isomer or an isolate isomer thereof. 
     
     
         2 . A pharmaceutical composition comprising a therapeutically effective amount the compound of  claim 1 . 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the composition is formulated for oral administration. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the composition is formulated for parenteral administered composition. 
     
     
         5 . The pharmaceutical composition of  claim 2 , further comprising a pharmaceutically acceptable excipient. 
     
     
         6 . A method for treating a subject with a bacterial infection, comprising administering to the subject a therapeutically effective amount of the pyrazinamide conjugate of  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein the bacterial infection is tuberculosis. 
     
     
         8 . The method of  claim 6 , wherein the bacterial infection is caused by one or more bacteria selected from the group consisting of  Mycobacterium marinum, Mycobacterium fortuitum, Mycobacterium tuberculosis, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumonia, Proteus vulgaris, Pseudomonas aeruginosa,  and  Proteus vulgaris.    
     
     
         9 . A method for treating a subject with a bacterial infection, comprising administering to the subject the pharmaceutical composition of  claim 2 . 
     
     
         10 . The method of  claim 9 , wherein the bacterial infection is tuberculosis. 
     
     
         11 . The method of  claim 9 , wherein the bacterial infection is caused by one or more bacteria selected from the group consisting of  Mycobacterium marinum, Mycobacterium fortuitum, Mycobacterium tuberculosis, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumonia, Proteus vulgaris, Pseudomonas aeruginosa,  and  Proteus vulgaris.    
     
     
         12 . The method of  claim 9 , wherein the composition is administered to the subject according to a regimen selected from 7 days per week for 8 weeks, 5 days per week for 8 weeks, 3 times per week for 7 weeks, or 7 days per week for 2 weeks then twice weekly for 6 weeks. 
     
     
         13 . The method of  claim 9 , wherein a second therapeutic is jointly administered to the subject serially or in combination or alternation with the pyrazinamide conjugate.