| abstract |
New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formula (I): M-L-Q, a resolved stereoisomer thereof or mixture of one or more such stereoisomers, and pharmaceutically acceptable salts thereof, wherein M is an immunophilin-binding group comprising a moiety of formula (II); G is independently selected from the group consisting of (a), (b), and (c); 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 CH2; B?1 and B2¿ 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 R2 to carbon 9; R?1, R2, and R3¿ 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 M1 to M2 through covalent bonds to either R1, R2, not necessarily the same in each of M?1 and M2¿. |