Novel antibacterial agents for the treatment of gram positive infections

Abstract

The present invention relates to novel lipopeptide compounds, pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The compounds of the invention are particularly useful against a variety of bacteria, including resistant strains. The compounds are useful as antibacterial agents against Clostridium difficile.

What is claimed is: 
     
         1 . A compound of Formula I 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof, wherein:
 R is: 
 
       
         
           
           
               
               
           
         
         A is chosen from alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, and NHR A ; and 
         R A  is chosen from alkyl and cycloalkyl. 
       
     
     
         2 . The compound of  claim 1   
       wherein:
 R is: 
 
       
         
           
           
               
               
           
         
          and wherein v is an integer from 3 to 7. 
       
     
     
         3 . A compound of Formula (II) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         4 . A pharmaceutical composition comprising a compound according to  claim 3 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         5 . A method of treating or preventing a bacterial infection comprising administering to a subject in need thereof a therapeutically-effective amount of the pharmaceutical composition according to  claim 4 . 
     
     
         6 . The method according to  claim 5 , wherein the subject is a human, an animal, a cell culture, or a plant. 
     
     
         7 . The method according to  claim 6 , wherein the subject is a human. 
     
     
         8 . The method according to  claim 5 , wherein the bacterial infection is caused by a gram-positive bacteria. 
     
     
         9 . The method according to  claim 8 , wherein the bacteria is a  Clostridium difficile  strain. 
     
     
         10 . The method according to  claim 9 , wherein the  Clostridium difficile  strain is a Nap1  Clostridium difficile  strain. 
     
     
         11 . The method according to  claim 8 , wherein the bacteria is an antibiotic resistant bacteria. 
     
     
         12 . The method according to  claim 11 , wherein the antibiotic resistant bacteria is daptomycin resistant  Staphylococcus aureus,  daptomycin resistant  Enterococcus faecium,  daptomycin resistant  Enterococcus. faecalis,  methicillin resistant  Staphylococcus aureus,  or a mixture of bacteria comprising at least one of the antibiotic resistant bacteria. 
     
     
         13 . The method according to  claim 11 , wherein the antibiotic-resistant bacteria is resistant to vancomycin, methicillin, glycopeptide antibiotics, penicillin or daptomycin. 
     
     
         14 . The method according to  claim 8 , wherein the bacterial infection is  Clostridium Difficile  Associated Disease (CDAD). 
     
     
         15 . The method according to  claim 14 , wherein the  Clostridium Difficile  Associated Disease arises from or is exacerbated by a Nap1  Clostridium difficile  infection.