Tuberculosis treatment using pleuromutilin derivatives

Abstract

A method of preventing or treating diseases caused by Mycobacterium , comprising administering to a subject in need of such treatment an effective amount of a pleuromutilin.

We claim: 
     
         1 . A compound selected from the group consisting of compounds of formulae as set out in TABLE 1: 
       
         
           
                 
               
                   TABLE 1 
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . A compound of formula 
       
         
           
           
               
               
           
         
         wherein
 the dotted line is a bond (double bond between positions a=b), R 1A  is hydrogen and R 2A  is not present, or 
 the dotted line is no bond (single bond between positions a-b) and R 1A  and R 2A  independently of each other are hydrogen, halogen or deuterium, 
 R 3A  is (C 1-6 )alkyl, 
 R 4A  is hydrogen, (C 1-6 )alkyl, a group —C(═NH)—NH 2 , or the residue of an amino acid, 
 R 5A  is hydrogen, or 
 R 4A  and R 5A  together are a group ═CH—NH 2 , 
 R 6A  is hydrogen or deuterium, and 
 m A  is 0, 1, 2, 3, 4, or 5. 
 
       
     
     
         3 . A compound of formula 
       
         
           
           
               
               
           
         
         wherein
 R 1C  has the meaning of R 1A  as defined in  claim 2 , 
 R 2C  has the meaning of R 2A  as defined in  claim 2 , 
 the dotted line has the meaning as defined in  claim 2 , 
 R 4C  has the meaning of R 6A  as defined in  claim 2 , and 
 R 3C  is amino, (C 1-4 )alkylamino, di(C 1-4 )alkylamino, the residue of an amino acid, hydroxy, or (C 1-4 )alkoxy. 
 
       
     
     
         4 . A compound of formula 
       
         
           
           
               
               
           
         
         wherein
 R 1D  has the meaning of R 1A  as defined in  claim 2 , 
 R 2D  has the meaning of R 2A  as defined in  claim 2 , 
 R 4D  has the meaning of R 6A  as defined in  claim 2 , 
 the dotted line has the meaning as defined in  claim 2 , and 
 R 3D  is aliphatic heterocyclyl of 4 to 8 ring members, and comprising one nitrogen atom as the heteroatom, or (C 4-8 )cycloalkyl, which heterocyclyl or cycloalkyl is substituted by hydroxy or oxo. 
 
       
     
     
         5 . The compound of  claim 2  in the form of a salt. 
     
     
         6 . The compound of  claim 2  for use as a pharmaceutical. 
     
     
         7 . A pharmaceutical composition comprising a compound of  claim 2  in association with at least one pharmaceutical excipient. 
     
     
         8 . The pharmaceutical composition according to  claim 6 , further comprising another pharmaceutically active agent. 
     
     
         9 . A pharmaceutical composition comprising a pleuromutilin in association with at least one pharmaceutical excipient, and further comprising another pharmaceutically active agent useful in the treatment of  Mycobacterium  infections. 
     
     
         10 . The compound of  claim 2  for use in the preparation of a medicament for the treatment of microbial diseases. 
     
     
         11 . A method of treatment of microbial diseases, wherein said method comprises administering to a subject in need of such treatment an effective amount of a compound of  claim 2 .