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

申请人： Marina Biotech, Inc.

发明人： Quay, Steven ,  Houston, Michael ,  Harvie, Pierrot ,  Adami, Roger ,  Fam, Renata ,  Prieve, Mary ,  Fosnaugh, Kathy ,  Seth, Shaguna

IPC分类号： A61K48/00 ,  A61K47/06 ,  A61K9/127 ,  C12N15/88 ,  C07C279/14 ,  C07D213/40 ,  C07D233/26 ,  C12N15/11

CPC分类号： A61K47/183 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/1272 ,  A61K31/7088 ,  A61K47/18 ,  A61K47/22 ,  A61K47/28 ,  A61K47/44 ,  A61K48/0025 ,  A61K48/0033 ,  C07C235/02 ,  C07C279/12 ,  C07C279/14 ,  C07D213/40 ,  C07D213/56 ,  C07D233/26 ,  C07D233/64 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/1138 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  Y10S514/943

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。

公开(公告)号：EP2494993B1

公开(公告)日：2018-08-01

申请号：EP12158867.7

申请日：2008-05-02

申请人： Marina Biotech, Inc.

发明人： Quay, Steven ,  Houston, Michael ,  Harvie, Pierrot ,  Adami, Roger ,  Fam, Renata ,  Prieve, Mary ,  Fosnaugh, Kathy ,  Seth, Shaguna

IPC分类号： A61K48/00 ,  A61K47/06 ,  A61K9/127 ,  C12N15/88 ,  C07C279/14 ,  C07D213/40 ,  C07D233/26 ,  C12N15/11

CPC分类号： A61K47/183 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/1272 ,  A61K31/7088 ,  A61K47/18 ,  A61K47/22 ,  A61K47/28 ,  A61K47/44 ,  A61K48/0025 ,  A61K48/0033 ,  C07C235/02 ,  C07C279/12 ,  C07C279/14 ,  C07D213/40 ,  C07D213/56 ,  C07D233/26 ,  C07D233/64 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/1138 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  Y10S514/943

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, €ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ€ƒ R 3 -(C=O)-Xaa-Z-R 4 €ƒ€ƒ€ƒ€ƒ€ƒFormula 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.

公开(公告)号：EP2494993A3

公开(公告)日：2012-12-19

申请号：EP12158867.7

申请日：2008-05-02

申请人： Marina Biotech, Inc.

发明人： Quay, Steven ,  Houston, Michael ,  Harvie, Pierrot ,  Adami, Roger ,  Fam, Renata ,  Prieve, Mary ,  Fosnaugh, Kathy ,  Seth, Shaguna

IPC分类号： A61K48/00 ,  A61K47/06 ,  A61K9/127 ,  C12N15/88 ,  C07C279/14 ,  C07D213/40 ,  C07D233/26 ,  C12N15/11

CPC分类号： A61K47/183 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/1272 ,  A61K31/7088 ,  A61K47/18 ,  A61K47/22 ,  A61K47/28 ,  A61K47/44 ,  A61K48/0025 ,  A61K48/0033 ,  C07C235/02 ,  C07C279/12 ,  C07C279/14 ,  C07D213/40 ,  C07D213/56 ,  C07D233/26 ,  C07D233/64 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/1138 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  Y10S514/943

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： 本发明提供了包含式I所示结构的化合物，用于将治疗性核酸，一种或多种药物剂或生物活性剂递送至细胞中，R 3 - （C = O）-Xaa-Z-R 4 式I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，正 - 精氨酸，鸟氨酸，高赖氨酸，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 ; R3独立地为衍生自天然存在或合成的脂质，磷脂，糖脂，三酰甘油，甘油磷脂，鞘脂，神经酰胺，鞘磷脂，脑苷脂或神经节苷脂的亲脂性尾部，其中所述尾部可含有类固醇; 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; R4独立地为衍生自天然存在或合成的脂质，磷脂，糖脂，甘油三酯，甘油磷脂，鞘脂，神经酰胺，鞘磷脂，脑苷脂或神经节苷脂的亲脂性尾部，其中尾部可含有类固醇; 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R3和R4都是亲脂性尾部; 和Z是NH，O，S，-CH 2 S - ， - CH 2 S（O） - 或由1-40个选自氢，碳，氧，氮和硫原子的原子组成的有机连接体; 及其盐。