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    • 2. 发明申请
    • NOVEL AMIDE-BASED CATIONIC LIPIDS
    • 新型基于阳离子的阳离子脂肪
    • WO1997003939A1
    • 1997-02-06
    • PCT/US1996012087
    • 1996-07-22
    • GENTA INCORPORATEDSCHWARTZ, David, AaronDAILY, William, S.DWYER, Brian, PatrickSRINIVASAN, KumarBROWN, Bob, Dale
    • GENTA INCORPORATED
    • C07C49/105
    • B82Y5/00A61K9/1272C07C237/06C07C237/10C07C237/22C07K5/06086C07K5/0815
    • The present invention provides novel amide-based cationic lipids of general structure (I) or a salt, or solvate, or enantiomers thereof wherein: (a) Y is a direct link or an alkylene of 1 to about 20 carbon atoms; (b) R1 is H or a lipophilic moiety; (c) R2, R3, and R4 are positively charged moieties, or at least one but not all of R2, R3, or R4 is a positive moiety and the remaining are independently selected from H, an alkyl moiety of 1 to about 6 carbon atoms, or a heterocyclic moiety of about 5 to about 10 carbon atoms; (d) n and p are independently selected integers from 0 to 8, such that the sum of n and p is from 1 to 16; (e) X is an anion or polyanion and (f) m is an integer from 0 to a number equivalent to the positive charge(s) present on the lipid; provided that if Y is a direct link and the sum of n and p is 1 then one of either R3 or R4 must have an alkyl moiety of at least 10 carbon atoms. The present invention further provides compositions of these lipids with polyanionic macromolecules, methods for interfering with protein expression in a cell utilizing these compositions and a kit for preparing the same.
    • 本发明提供了通式(I)的新型酰胺类阳离子脂质或其盐或溶剂合物或其对映异构体,其中:(a)Y为1至约20个碳原子的直链或亚烷基; (b)R 1为H或亲油部分; (c)R 2,R 3和R 4为带正电荷的部分,或至少一个但不全部为R 2,R 3或R 4为正部分,其余独立地选自H,1至约6个碳原子的烷基部分 原子或约5至约10个碳原子的杂环部分; (d)n和p独立地选自0至8的整数,使得n和p之和为1至16; (e)X 1是阴离子或聚阴离子,(f)m是0至等于脂质上存在的正电荷数的整数; 条件是如果Y是直链,并且n和p之和为1,则R3或R4之一必须具有至少10个碳原子的烷基部分。 本发明还提供了这些脂质与聚阴离子大分子的组合物,利用这些组合物干扰细胞中的蛋白质表达的方法和用于制备该组合物的试剂盒。