Amino acid lipids and uses thereof
    6.
    发明公开
    Amino acid lipids and uses thereof 审中-公开
    Aminosäure-Lipide und ihre Verwendungen

    公开(公告)号:EP2494993A2

    公开(公告)日:2012-09-05

    申请号:EP12158867.7

    申请日:2008-05-02

    摘要: The present invention provides a compound comprising the structure shown in Formula I for use in delivering a therapeutic nucleic acid, one or more drug agents, or a biologically active agent to a cell,

            R 3 -(C=O)-Xaa-Z-R 4      Formula I

    wherein
    Xaa is histidine, 1-methylhistidine, pyridylalanine, lysine, arginine, homoarginine, nor-norarginine, ornithine, homolysine, asparagine, N ethylasparagine, glutamine, 4-aminophenylalanine, and nor-arginine, or an N-methylated version thereof; R 3 is independently a lipophilic tail derived from a naturally-occurring or synthetic lipid, phospholipid, glycolipid, triacylglycerol, glycerophospholipid, sphingolipid, ceramide, sphingomyelin, cerebroside, or ganglioside, wherein the tail may contain a steroid; or a substituted or unsubstituted C(3-22)alkyl, C(6-12)cycloalkyl, C(6-12)cycloalkyl-C(3-22)alkyl, C(3-22)alkenyl, C(3-22)alkynyl, C(3-22)alkoxy, or C(6-12)alkoxy-C(3-22)alkyl;
    R 4 is independently a lipophilic tail derived from a naturally-occurring or synthetic lipid, phospholipid, glycolipid, triacylglycerol, glycerophospholipid, sphingolipid, ceramide, sphingomyelin, cerebroside, or ganglioside, wherein the tail may contain a steroid; or a substituted or unsubstituted C(3-22)alkyl, C(6-12)cycloalkyl, C(6-12)cycloalkyl-C(3-22)alkyl, C(3-22)alkenyl, C(3-22)alkynyl, C(3-22)alkoxy, or C(6-12)alkoxy-C(3-22)alkyl;
    wherein both R 3 and R 4 are lipophilic tails; and
    Z is NH, O, S, -CH 2 S-, -CH 2 S(O)-, or an organic linker consisting of 1-40 atoms selected from hydrogen, carbon, oxygen, nitrogen, and sulfur atoms;
    and salts thereof.

    摘要翻译: 本发明提供一种化合物,其包含用于将治疗性核酸,一种或多种药物或生物活性剂递送至细胞的式I所示的结构,ƒ€ƒ€ƒ€ƒ€ ƒ€ƒR 3 - (C = O)-Xaa-ZR 4€ƒ€ƒ€ƒ€ƒF其中Xaa是组氨酸,1-甲基组氨酸,吡啶丙氨酸,赖氨酸,精氨酸,高精氨酸,去甲炔诺胺,鸟氨酸, 天冬酰胺,N-乙基天冬酰胺,谷氨酰胺,4-氨基苯丙氨酸和正精氨酸,或其N-甲基化形式; R 3独立地是衍生自天然存在的或合成的脂质,磷脂,糖脂,三酰基甘油,甘油磷脂,鞘脂,神经酰胺,鞘磷脂,脑脊液或神经节苷脂的亲脂性尾巴,其中尾部可以含有类固醇; 或取代或未取代的C(3-22)烷基,C(6-12)环烷基,C(6-12)环烷基-C(3-22)烷基,C(3-22)烯基,C(3-22) )炔基,C(3-22)烷氧基或C(6-12)烷氧基-C(3-22)烷基; R 4独立地是衍生自天然存在的或合成的脂质,磷脂,糖脂,三酰基甘油,甘油磷脂,鞘脂,神经酰胺,鞘磷脂,脑脊液或神经节苷脂的亲脂性尾巴,其中尾部可以含有类固醇; 或取代或未取代的C(3-22)烷基,C(6-12)环烷基,C(6-12)环烷基-C(3-22)烷基,C(3-22)烯基,C(3-22) )炔基,C(3-22)烷氧基或C(6-12)烷氧基-C(3-22)烷基; 其中R 3和R 4都是亲脂尾料; 或Z为NH,O,S,-CH 2 S - , - CH 2 S(O) - 或由选自氢,碳,氧,氮和硫原子的1-40个原子组成的有机接头; 及其盐。