Antibacterial mutilins

Abstract

A compound of formula (I) wherein R and R 2 and the attached nitrogen atom form pyrrolidinyl or piperidinyl. R 1 is a group of formula (II). R 3 and R′ 3 are hydrogen, deuterium or halogen. R 4 , R 5 and R 10 are independently of each other hydrogen or alkyl. R 6 , R 7 and R 8 are hydrogen or deuterium. R 9 is amino, alkyl, aryl, heterocyclyl or mercapto. If X is oxygen, R 9 is additionally hydrogen; R′ 10 is alkyl, X is sulphur, oxygen, NR 10 , or N+(R′ 10 ) 2 ; Y is sulphur or oxygen, and m is 0, 1 or 2, with the proviso that, when R and R 2 and the attached nitrogen atom form piperidinyl, m is O, Y is S and Y is attached in position 3 of the piperidine ring, that group of formula (I) which is attached to the piperidine ring via the residue Y is either in the (S)-configuration or in the (R)-configuration, preferably in the (S)-configuration which is useful as antimicrobial, antibacterial.

1 . A compound of formula I p   
     
       
         
         
             
             
         
       
       wherein 
       R 3p  and R′ 3p  are hydrogen, deuterium, or halogen; 
       R 5p  is hydrogen or one or more substituents; 
       R 6p , R 7p , and R 8p  are hydrogen or deuterium; and 
       if the group attached to the piperidine ring via the sulphur atom is in position 3 of said piperidine ring and R 5p  is hydrogen, then the group attached to the sulphur atom is either in the (S)-configuration or in the (R)-configuration. 
     
   
   
       2 . A compound of  claim 1  in the form of a salt, or in the form of a salt and in the form of a solvate, or in the form of a solvate. 
   
   
       3 . A pharmaceutical composition comprising an effective amount of a compound of  claim 1  and at least one pharmaceutically acceptable carrier or diluent therefor. 
   
   
       4 . A pharmaceutical composition of  claim 3  in free form or in the form of a pharmaceutically acceptable salt. 
   
   
       5 . A compound of formula 
     
       
         
         
             
             
         
       
       wherein 
       R and R 2  together with the nitrogen atom to which they are attached form pyrrolidinyl or piperidinyl, 
       R 1  is a group of formula 
     
     
       
         
         
             
             
         
       
       R 3  and R′ 3  are hydrogen, deuterium or halogen, 
       R 4  is hydrogen or alkyl, 
       R 5  is hydrogen or alkyl, 
       R 6 , R 7  and R 8  are hydrogen or deuterium; 
       R 9  is amino, alkyl, aryl, heterocyclyl or mercapto; and, if X is oxygen, R 9  is additionally hydrogen; 
       R 10  is hydrogen or alkyl, 
       R′ 10  is alkyl, 
       X is sulphur, oxygen, NR 10 , or N + (R′ 10 ) 2 , 
       Y is sulphur or oxygen, and 
       m is 0, 1 or 2; 
       with the proviso that, when R and R 2  together with the nitrogen atom to which they are attached form piperidinyl, m is 0, Y is S and Y is attached in position 3 of said piperidine ring that group of formula I which is attached to the piperidine ring via the residue Y is either in the (S)-configuration or in the (R)-configuration, preferably in the (S)-configuration. 
     
   
   
       6 . A compound of formula I as defined in  claim 5 , wherein
 R 3 , R′ 3 , R 4 , R 5 , R 6 , R 7  and R 8  are hydrogen;
 R 1  is a group of formula 
   
     
       
         
         
             
             
         
       
       R and R 2  together with the nitrogen atom to which they are attached form piperidine or pyrrolidine; 
       R 9  is alkyl; 
       X is oxygen; 
       Y is sulphur; and 
       m is 0 or 1; 
       with the proviso that, when R and R 2  together with the nitrogen atom to which they are attached form piperidinyl, m is 0, Y is S and Y is attached in position 3 of said piperidine ring, that group of formula I which is attached to the piperidine ring via the residue Y is either in the (S)-configuration or in the (R)-configuration, preferably in the (S)-configuration. 
     
   
   
       7 . A method of prophylaxis or treatment of microbial diseases which comprises administering to a subject in need of such treatment an effective amount of a compound of  claim 1 .