18-Membered Macrocycles and Analogs Thereof

Abstract

The present invention relates generally to the 18-membered macrocyclic antimicrobial agents called Tiacumicins, specifically, OPT-80 (which is composed almost entirely of the R-Tiacumicin B), pharmaceutical compositions comprising OPT-80, and methods using OPT-80. In particular, this compound is a potent drug for the treatment of bacterial infections, specifically C. difficile infections.

1 - 16 . (canceled) 
     
     
         17 . A method of treating reoccurring diarrhea caused by  C. difficile  gastrointestinal infection in a human patient previously treated for the diarrhea,
 comprising orally administering to said patient a therapeutically effective amount of a compound having the formula (IV):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt combined with one or more pharmaceutically acceptable carriers, wherein the compound having formula (IV) is greater than 90% by weight stereomerically pure. 
       
     
     
         18 . The method of  claim 17 , wherein the method consists of administering to the human patient a therapeutically effective amount of the compound having formula (IV) or a pharmaceutically acceptable salt thereof combined with one or more pharmaceutically acceptable carriers. 
     
     
         19 . The method of  claim 17 , wherein the compound of formula (IV) is formulated as a tablet. 
     
     
         20 . The method of  claim 17 , wherein the compound of formula (IV) is formulated as a capsule. 
     
     
         21 . The method of  claim 17 , wherein the compound of formula (IV) is greater than 93% by weight stereomerically pure. 
     
     
         22 . The method of  claim 17 , wherein the compound of formula (IV) is greater than 95% by weight stereomerically pure. 
     
     
         23 . The method of  claim 17 , wherein the compound of formula (IV) is greater than 97% by weight stereomerically pure. 
     
     
         24 . The method of  claim 17 , wherein the compound of formula (IV) is substantially free of other diastereomers of the compound. 
     
     
         25 . The method of  claim 17 , wherein the patient suffers from colitis. 
     
     
         26 . A method of treating reoccurring diarrhea caused by  C. difficile  gastrointestinal infection in a human patient previously treated for the diarrhea,
 consisting of orally administering to said patient a therapeutically effective amount of a compound having the formula (IV):   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof combined with one or more pharmaceutically acceptable carriers, wherein the compound of the formula (IV) is greater than 93% by weight stereomerically pure. 
       
     
     
         27 . The method of  claim 26 , wherein the compound of formula (IV) is formulated as a tablet. 
     
     
         28 . The method of  claim 26 , wherein the compound is formulated as a capsule. 
     
     
         29 . The method of  claim 26 , wherein the compound of formula (IV) is greater than 95% by weight stereomerically pure. 
     
     
         30 . The method of  claim 26 , wherein the compound of formula (IV) is greater than 97% by weight stereomerically pure. 
     
     
         31 . The method of  claim 26 , wherein the compound of formula (IV) is substantially free of other diastereomers of the compound. 
     
     
         32 . The method of  claim 26 , wherein the patient suffers from colitis.