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 R1, R2, R3, R5, R6, R8, M1, M2, M3, M4, M5, M6 and M7 are each independently a member selected from the group consisting of H, C1-6 alkyl, OH and C1-6 hydroxyalkyl; R4, R7 and R9 are each independently selected from the group consisting of C1-6 alkoxy and OH; R10 is a member selected from the group consisting of H, —OH, —OP(O)Me2,—O—(CH2)n—OH and —O—(CH2)m—O—(CH2)o—CH3, wherein subscripts n and m are each independently from 2 to 8 and subscript o is from 1 to 6; each of L1 and L4 are independently selected from the group consisting of:wherein each M8 is independently a member selected from the group consisting of C1-6 alkyl, OH and C1-6 hydroxyalkyl; each of L2 and L3 are independently selected from the group consisting of:and salts, hydrates, isomers, metabolites, N-oxides and prodrugs thereof.

What is claimed: 
     
         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.