Antimicrobial agents

Abstract

Antimicrobial compounds of formula I are disclosed: R 1 —X—R 2 wherein X is a group comprising of from about 4 to about 10 amino acids, wherein at least one of the amide (—CONH—) linkages is replaced by —CR a R b NR c —; R a , R b , and R c are each independently hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxycarbonyl, aryl, or heterocycle; and R 1 and R 2 are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group; or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising such compounds or salts, and methods of using such compounds or salts to treat a bacterial infection.

We claim:  
     
         1 . A method of treating or preventing a bacterial infection in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of formula I:  
       R 1 —X—R 2    wherein X is a peptide comprising of from about 4 to about 10 amino acids, wherein at least one of the amide (—CONH—) linkages is replaced by —CR a R b NR c —;    R a , R b , and R c  are each independently hydrogen, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 6 )alkoxycarbonyl, aryl, or heterocycle; and    R 1  and R 2  are each independently hydrogen, a saccharide, a lipid, a solubilizing agent, or a suitable protecting group;    or a pharmaceutically acceptable salt thereof.    
     
     
         2 . The method of  claim 1 , wherein X is:  
       -A-B-C-D-E-  wherein each of A, B, C, D, and E is independently an amino acid.    
     
     
         3 . The method of  claim 2  wherein each of A, B, C, D, and E is independently a natural amino acid.  
     
     
         4 . The method of  claim 2  wherein at least one of A, B, C, D, or E is an unnatural amino acid.  
     
     
         5 . The method of  claim 2  wherein each amino acid is in the L-configuration.  
     
     
         6 . The method of  claim 2  wherein at least one of amino acids is in the D-configuration.  
     
     
         7 . The method of  claim 2 , wherein the amide bond connecting D to E is replaced by —CR a R b NR c —.  
     
     
         8 . The method of  claim 2  wherein A is an amino acid selected from the group consisting of naphthylalanine, aminomethyl benzoic acid, tyrosine, and phenylalanine.  
     
     
         9 . The method of  claim 2  wherein D is phenylalanine.  
     
     
         10 . The method of  claim 2  wherein at least one of A, B, C, D, and E is a D amino acid.