Synthetic multimerizing agents

Abstract

New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formula M—L—Q where M is a synthetic ligand for an FKBP protein

What is claimed is:  
     
         1 . A compound of the formula I:  
       M—L—Q   I  
       a resolved stereoisomer thereof or mixture of one or more such stereoisomers, and pharmaceutically acceptable salts thereof, wherein 
 M is an immunophilinbinding group comprising a moiety of the formula II:  
                     
 G is independently selected from the group consisting of:  
                     
 Q comprises a moiety of formula II, a naturally occurring macrocyclic FKBP ligand or derivative thereof, or is a synthetic FKBP ligand of formula III:  
                     
 n=1 or 2;  
 X=O, NH or CH 2 ;  
 B 1  and B 2  are independently H or aliphatic, heteroaliphatic, aryl or heteroaryl;  
 Y=O, S, NH, —NH(C═O)—, —NH(C═O)—O—, —NH(SO 2 )— or NR 3 , or represents a covalent bond from R 2  to carbon 9;  
 R 1 , R 2 , and R 3  are the same or different and are independently aliphatic, heteroaliphatic, aryl or heteroaryl; and,  
 L is a linker moiety covalently linking monomers M to Q or covalently linking M 1  to M 2  through covalent bonds to either R 1  or R 2 , not necessarily the same in each of M 1  and M 2 .