Macrocyclic lactone compounds and methods for their use

Abstract

The present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula: wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 8 , M 1 , M 2 , M 3 , M 4 , M 5 , M 6 and M 7 are each independently a member selected from the group consisting of H, C 1-6 alkyl, —OH and C 1-6 hydroxyalkyl; R 4 , R 7 and R 9 are each independently selected from the group consisting of C 1-6 alkoxy and OH; R 10 is a member selected from the group consisting of H, —OH, —OP(O)Me 2 , —O—(CH 2 ) n —OH and —O—(CH 2 ) m —O—(CH 2 ) o —CH 3 , wherein subscripts n and m are each independently from 2 to 8 and subscript o is from 1 to 6; each of L 1 and L 4 are independently selected from the group consisting of: wherein each M 8 is independently a member selected from the group consisting of C 1-6 alkyl, OH and C 1-6 hydroxyalkyl; each of L 2 and L 3 are independently selected from the group consisting of: and salts, hydrates, isomers, metabolites, N-oxides and prodrugs thereof.

What is claimed is: 
     
         1 . A method for the treatment or prevention of acute or chronic transplant rejection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
         or a salt, isomer, or N-oxide thereof, thereby treating or preventing the transplant rejection.