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.

What is claimed is: 
     
         1 . A substantially stereomerically pure compound having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         2 . The compound of  claim 1 , which is greater than 90% stereomeric purity. 
     
     
         3 . The compound of  claim 1 , which is greater than 95% stereomeric purity. 
     
     
         4 . The compound of  claim 1 , which is greater than 99% stereomeric purity. 
     
     
         5 . A composition comprising a substantially stereomerically pure compound having the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
       
     
     
         6 . The composition of  claim 5 , wherein the compound is greater than 90% stereomeric purity. 
     
     
         7 . The composition of  claim 5 , wherein the compound is greater than 95% stereomeric purity. 
     
     
         8 . The composition of  claim 5 , wherein the compound is greater than 99% stereomeric purity. 
     
     
         9 . The composition of  claim 5  further comprising a pharmaceutically acceptable carrier. 
     
     
         10 . The composition of  claim 5  further comprising 0-20% of Tiacumicin B related compounds. 
     
     
         11 . The composition of  claim 10 , wherein said Tiacumicin B related compounds is selected from the group consisting of Lipiarmycin A4 and C-19 Ketone. 
     
     
         12 . The composition of  claim 5  further comprised of an additional agent selected from the group consisting of an antimicrobial agent and an antifungal agent. 
     
     
         13 . The composition of  claim 5  suitable for oral administration. 
     
     
         14 . The composition of  claim 5  suitable for parenteral administration. 
     
     
         15 . The composition of  claim 5 , wherein the compound is present in an amount of about 0.015-0.25 μg/mL. 
     
     
         16 . A method for treating bacterial infections in a mammal, which comprises administering to said mammal a composition comprising a therapeutically effective amount of said composition of  claim 5 .