Tuberculosis treatment

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.

1 . Use of a pleuromutilin in the preparation of a medicament for the treatment of diseases caused by  Mycobacterium.    
   
   
       2 . A method of treating diseases mediated by  Mycobacterium , comprising administering to a subject in need of such treatment an effective amount of a pleuromutilin.  
   
   
       3 . A method according to  claim 2  wherein  Mycobacterium  is  Mycobacterium tuberculosis.    
   
   
       4 . A method according to  claim 2  wherein a pleuromutilin is a compound comprising the basic structural elements as set out in formula  
     
       
         
         
             
             
         
       
     
     wherein R is vinyl or ethyl and the dotted line is a bond or is no bond.  
   
   
       5 . Use or a method according to  claim 4  wherein a pleuromutilin is selected from the group consisting of 
 a compound of formula                          a compound of formula,                          a compound of formula                          a compound of formula                          a compound of formula                          a compound of formula                          a compound of formula                          a compound of formula                          a compound of formula                          and    a compound of                          
   
   
       6 . A compound selected from the group consisting of compounds of formulae as set out in TABLE 1:  
     
       
         
               
             
                 TABLE 1 
               
                   
               
                   
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                   
               
           
              
              
              
             
             
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
   
   
       7 . 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.  
 
   
   
       8 . A 14-O-(oximino-(C 3-8 )cycloalkyl-sulfanylmethylcarbonyl)-pleuromutilin and a 14-O-(hydrazono-(C 3-8 )cycloalkyl-sulfanylmethylcarbonyl)-pleuromutilin.  
   
   
       9 . A compound of formula  
     
       
         
         
             
             
         
       
       wherein  
       R 1B  has the meaning of R 1A  as defined in  claim 7 ,  
       R 2B  has the meaning of R 2A  as defined in  claim 7 ,  
       R 10B  has the meaning of R 6A  as defined in  claim 7 ,  
       the dotted line has the meaning as defined in  claim 7 ,  
       m B  has the meaning of m a  as defined above,  
       R 3B  is hydrogen or (C 1-6 )alkyl,  
       X B  is —O—R 4B  or —NR 5B R 6B ,  
       R 4B  is hydrogen or (C 1-6 )alkyl, optionally substituted by a group —NR 7B R 8B ,  
       R 5B  and R 6B  independently of each other are (C 1-4 )alkyl,  
       R 7B  and R 8B  independently of each other are (C 1-4 )alkyl, or  
       R 7B  and R 8B  together with the nitrogen atom to which they are attached form aliphatic heterocyclyl, having 5 to 8 ring members, and  
       R 9B  is hydrogen or (C 1-4 )alkyl.  
     
   
   
       10 . A compound of formula  
     
       
         
         
             
             
         
       
       wherein  
       R 1C  has the meaning of R 1A  as defined in  claim 7 ,  
       R 2C  has the meaning of R 2A  as defined in  claim 7 ,  
       the dotted line has the meaning as defined in  claim 7 ,  
       R 4C  has the meaning of R 6A  as defined in  claim 7 , 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.  
     
   
   
       11 . A compound of formula  
     
       
         
         
             
             
         
       
       wherein  
       R 1D  has the meaning of R 1A  as defined in  claim 7 ,  
       R 2D  has the meaning of R 2A  as defined in  claim 7 ,  
       R 4D  has the meaning of R 6A  as defined in  claim 7 ,  
       the dotted line has the meaning as defined in  claim 7 , 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.  
     
   
   
       12 . A compound of  claim 7  in the form of a salt.  
   
   
       13 . A compound of  claim 7  for use as a pharmaceutical.  
   
   
       14 . A pharmaceutical composition comprising a compound of  claim 7  in association with at least one pharmaceutical excipient.  
   
   
       15 . A pharmaceutical composition according to  claim 13 , further comprising another pharmaceutically active agent.  
   
   
       16 . 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.  
   
   
       17 . A compound of  claim 7  for use in the preparation of a medicament for the treatment of microbial diseases.  
   
   
       18 . A method of treatment of microbial diseases, which method comprises administering to a subject in need of such treatment an effective amount of a compound of  claim 7.