D,L-α-tocopheryl-β-cyanoethyl-N,N-diisopropylphosphoramidite | 142386-74-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: D,L-α-tocopheryl-β-cyanoethyl-N,N-diisopropylphosphoramidite
• 英文别名: vitamin E；D,L-α-tocopheryl β-cyanoethyl N,N-diisopropyl-phosphoramidite；3-[[Di(propan-2-yl)amino]-[[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-yl]oxy]phosphanyl]oxypropanenitrile
• CAS: 142386-74-1
• 化学式: C₃₈H₆₇N₂O₃P
• 分子量: 630.935
• InChiKey: USUSEQXJHLFSON-UHFFFAOYSA-N

物化性质

• 沸点：
  668.5±65.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  12.5
• 重原子数：
  44
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  54.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  DL-α-生育酚 、 2-氰乙基N,N-二异丙基氯亚磷酰胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以0.21 g的产率得到D,L-α-tocopheryl-β-cyanoethyl-N,N-diisopropylphosphoramidite
  参考文献：
  名称：

  使用笼状siRNA修饰单个末端维生素E的基因表达的光化学调控。

  摘要：

  合理设计和合成了在5'末端具有单个光不稳定接头和/或维生素E（vitE）修饰的笼状siRNA。这些几乎无活性的笼状siRNA已成功用于光调节细胞中萤火虫荧光素酶和GFP基因的表达，使基因沉默活性提高了18.6倍，这是迄今为止报道的基因沉默效率的最佳光调制方法之一。siRNA跟踪和vitE竞争实验表明，vitE修饰的siRNA的失活不是由于vitE的庞大部分所致。相反，通过阻止siRNA /脂质复合物的解离和/或siRNA释放，vitE结合蛋白的参与对笼中siRNA失活有很大贡献。

  DOI：

  10.1002/anie.201510921

文献信息

• ADJUVANT IN THE FORM OF A LIPID-MODIFIED NUCLEIC ACID
  申请人：Hoerr Ingmar

  公开号：US20070280929A1

  公开（公告）日：2007-12-06

  The present invention relates to an immune-stimulating adjuvant in the form of a lipid-modified nucleic acid, optionally in combination with further adjuvants. The invention relates further to a pharmaceutical composition and to a vaccine, each containing an immune-stimulating adjuvant according to the invention, at least one active ingredient and optionally a pharmaceutically acceptable carrier and/or further auxiliary substances and additives and/or further adjuvants. The present invention relates likewise to the use of the pharmaceutical composition according to the invention and of the vaccine according to the invention for the treatment of infectious diseases or cancer diseases. Likewise, the present invention includes the use of the immune-stimulating adjuvant according to the invention in the preparation of a pharmaceutical composition for the treatment of cancer diseases or infectious diseases.

  本发明涉及一种免疫刺激佐剂，其形式为脂质修饰的核酸，可选地与其他佐剂结合。该发明还涉及一种含有根据本发明的免疫刺激佐剂、至少一种活性成分以及可选的药用载体和/或其他辅助物质和添加剂和/或其他佐剂的药物组合物和疫苗。本发明还涉及根据本发明的药物组合物和疫苗用于治疗传染病或癌症的用途。同样，本发明包括根据本发明的免疫刺激佐剂用于制备用于治疗癌症或传染病的药物组合物的用途。
• NUCLEIC ACID OF FORMULA (I): GlXmGn, OR (II): ClXmCn, IN PARTICULAR AS AN IMMUNE-STIMULATING AGENT/ADJUVANT
  申请人：CureVac AG

  公开号：US20200016264A1

  公开（公告）日：2020-01-16

  The present invention relates to a nucleic acid of the general formula (I): G l X m G n , or (II): C l X m C n , which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.

  本发明涉及一般式(I)：G l X m G n 或(II)：C l X m C n的核酸，该核酸可以通过脂质进行修饰。本发明的核酸作为免疫刺激剂，诱导先天免疫应答。本发明还涉及一种药物组合物（在第一实施例中），每种组合物包含本发明的免疫刺激剂与药用活性载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）的组合。在另一实施例中，创新的核酸与至少一种药用活性成分、药用可接受的载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）结合。因此，本发明涉及一种疫苗，该疫苗对应于本发明的药物组合物（第二实施例），其中药用活性成分诱导特异免疫应答（例如抗原）。本发明同样涉及利用本发明的核酸或药物组合物治疗传染病、自身免疫疾病、过敏或癌症疾病。
• Attachment of vitamin E derivatives to oligonucleotides during solid-phase synthesis
  作者：David W. Will、Tom Brown

  DOI：10.1016/s0040-4039(00)79068-x

  日期：1992.5

  attachment of Vitamin E to the 5′-, and 3′-ends of oligonucleotides, and the attachment of a Vitamin E moiety on an octamethylene spacer to the 5′-end, all during solid-phase synthesis. The effects on cellular uptake, distribution, and antiviral activity of the attachment of the extremely lipophilic Vitamin E moiety to phosphorothioate ‘antisense’ oligonucleotides are now being investigated.

  已经合成了在固相合成过程中允许维生素E与寡核苷酸的5'和3'末端连接以及八亚甲基间隔基上的维生素E部分与5'末端连接的化合物。 。现在正在研究极亲脂性维生素E部分与硫代磷酸酯“反义”寡核苷酸的附着对细胞摄取，分布和抗病毒活性的影响。
• Nucleic Acid of Formula (I): GIXmGn, or (II): CIXmCn, in Particular as an Immune-Stimulating Agent/Adjuvant
  申请人：Hoerr Ingmar

  公开号：US20090324584A1

  公开（公告）日：2009-12-31

  The present invention relates to a nucleic acid of the general formula (I): G l X m G n , or (II): C l X m C n , which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.

  本发明涉及一般式(I)：GlXmGn或(II)：ClXmCn的核酸，该核酸可以通过脂质进行修饰。本发明的核酸作为一种免疫刺激剂，诱导先天免疫应答。本发明进一步涉及一种药物组合物（在第一实施例中），每种组合物包含根据本发明的免疫刺激剂与药学活性载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）的组合。在另一实施例中，创新的核酸与至少一种药学活性成分、药学可接受的载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）结合。因此，本发明涉及一种疫苗，该疫苗对应于本发明的药物组合物（第二实施例），其中药学活性成分诱导特异免疫应答（例如抗原）。本发明同样涉及利用本发明的核酸或药物组合物用于治疗传染病、自身免疫疾病、过敏或癌症疾病。
• Nucleic acid comprising GlXmGn as an immune-stimulating agent/adjuvant
  申请人：Hoerr Ingmar

  公开号：US10441653B2

  公开（公告）日：2019-10-15

  The present invention relates to a nucleic acid of the general formula (I): GIXmGn, which may be modified by a lipid. The invention relates further to a pharmaceutical composition containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). The present invention can relate to a vaccine, which corresponds to a pharmaceutical composition of the invention, wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention can relate to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune disease, allergies or cancer diseases.

  本发明涉及通式 (I) 的核酸：GIXmGn 的核酸，该核酸可被脂质修饰。本发明还涉及一种药物组合物，该组合物含有根据本发明的免疫刺激剂与药用活性载体/载体（以及可选的进一步辅助物质、添加剂和/或进一步佐剂）。本发明可涉及一种疫苗，它与本发明的药物组合物相对应，其中的药物活性成分可诱导特异性免疫反应（如抗原）。本发明可涉及将本发明的核酸或根据本发明的药物组合物用于治疗传染性疾病、自身免疫性疾病、过敏或癌症疾病。