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    SYNTHETIC DERIVATIVES OF RAPAMYCIN AS MULTIMERIZING AGENTS FOR CHIMERIC PROTEINS WITH IMMUNOPHILIN-DERIVED DOMAINS
    1.
    发明公开
    SYNTHETIC DERIVATIVES OF RAPAMYCIN AS MULTIMERIZING AGENTS FOR CHIMERIC PROTEINS WITH IMMUNOPHILIN-DERIVED DOMAINS 失效
    合成雷帕霉素衍生物ALS多聚FOR PROTEIN物质WITH亲免素的次域CHIMERE

    公开(公告)号：EP0888303A1

    公开(公告)日：1999-01-07

    申请号：EP97907937.0

    申请日：1997-02-28

    申请人： ARIAD GENE THERAPEUTICS, INC.

    发明人： HOLT, Dennis, A. ,  KEENAN, Terence, P. ,  GUO, Tao ,  LABORDE, Edgardo ,  YANG, Wu

    IPC分类号： A61K31 ,  A61P37 ,  C07D207 ,  C07D211 ,  C07D401 ,  C07D405

    CPC分类号： C07D401/14 ,  C07D207/16 ,  C07D211/60 ,  C07D401/12 ,  C07D405/12

    摘要： 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¿.