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    • 10. 发明授权
    • DNA-binding polyamide drug conjugates
    • DNA结合聚酰胺药物共轭物
    • US07605125B2
    • 2009-10-20
    • US10506085
    • 2003-02-27
    • Zoltan SzekelyHumcha Krishnamurthy HariprakashaMarek W. CholodyChristopher Michejda
    • Zoltan SzekelyHumcha Krishnamurthy HariprakashaMarek W. CholodyChristopher Michejda
    • A61K38/16A61K38/02A61K51/00A61M36/14
    • A61K47/645
    • A conjugate of formula: V—(Y)a—Z-T: (I), T-X—B—(Y)a—Z-T′: (II), V—(Y)a Z—(Y′)a V′: (III), T-X—B—(Y)a—Z—(Y′)a—X′—B′-T′: (IV), V—(Y)a—Z—(Y′)a—X—B-T: (V), V—(Y)a—Z—X—B—Z′—(Y′)a—(V′)b: (VI), or (W)a—(Y)b—[(Z)c—(Y′)d—(X—B)e—(Y″)f—(Z′)g]h—(Y . . . )i—(W′)j: (VII), in which W and W′ are independently a DNA intercalator or terminal subunit, V and V′ are independently a DNA intercalator, X and X′ are independently a DNA alkylator, B and B′ are the same or different and each is a heteoaromatic residue that is attached to the Nterminus of an alkylator subunit (X or X′), Y, Y′, Y″ and Y′″ are independently a linker, T and T′ are independently terminal subunits, Z and Z′ are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of a conjugate of any of formulae (I)-(VII) or a composition comprising same.
    • 式(V)(Y)aZT:(I),TXB-(Y)aZ-T':(II),V-(Y)a Z-(Y')a V' TXB-(Y)aZ-(Y')a-X'-B'-T':(IV),V-(Y)aZ-(Y')aXBT:(V),V-(Y)aZXB- Z' - (Y')a-(V')b:(VI)或(W)a-(Y)b - [(Z)c-(Y')d-(XB)e-(Y' ')f-(Z')g] h-(Y。。)i-(W')j:(VII),其中W和W'独立地是DNA嵌入剂或末端亚单元,V和V' 独立地是DNA嵌入剂,X和X'独立地是DNA烷基化剂,B和B'是相同或不同的,并且各自是连接到烷基化子亚基(X或X'),Y,Y的N末端的芳香族残基 ',Y“和Y”独立地是连接体,T和T'独立地是末端亚单元,Z和Z'独立地是结合DNA的小沟的聚酰胺基团,a,b,c,d, f,g,i和j独立地为0〜5,e和h独立地为1〜5,包含式(I) - (VII)中任一式的结合物和载体的组合物,以及治疗癌症的方法 在哺乳动物中,包括施用有效的 量的式(I) - (VII)中任一项的缀合物或包含其的组合物。