N,N-Bis(N'-3-aminopropyl-4-aminobutyl) cholesteryl carbamate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N,N-Bis(N'-3-aminopropyl-4-aminobutyl) cholesteryl carbamate
• 英文别名: [(10R,13R,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] N,N-bis[4-(3-aminopropylamino)butyl]carbamate
• 化学式: C₄₂H₇₉N₅O₂
• 分子量: 686.122
• InChiKey: DYNCMSFNOLBHCB-XLPWBTRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  49
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  106
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N,N-Bis(4-aminobutyl) cholesteryl carbamate 、 丙烯腈 在 aluminum nickel 作用下， 以81%的产率得到N,N-Bis(N'-3-aminopropyl-4-aminobutyl) cholesteryl carbamate
  参考文献：
  名称：

  Cationic amphiphiles containing ester or ether-linked lipophilic groups

  摘要：

  提供了一种新型的阳离子两性分子，有助于将生物活性（治疗性）分子输送到细胞内。这些两性分子包含从类固醇、单或双烷胺基或烷基或酰基团衍生的亲脂基团；以及从胺、烷胺或多烷基胺衍生的在生理pH下可质子化的阳离子基团。还提供了通常通过将一个或多个阳离子两性分子的分散液与治疗分子接触而制备的治疗组合物。根据本发明的实践，可以将可输送到细胞内的治疗分子包括DNA、RNA和多肽。本发明的治疗组合物的代表性用途包括提供基因治疗，以及将反义多核苷酸或生物活性多肽输送到细胞中。关于用于基因治疗的治疗组合物，DNA通常以质粒的形式提供，以与阳离子两性分子结合。还公开了新型且高效的质粒构建物，包括那些在为临床炎症并发症复杂的情况下提供基因治疗方面特别有效的构建物。此外，描述了通过静脉给药治疗组合物来定位器官进行基因治疗的方法。

  公开号：

  US05840710A1

文献信息

• Cationic amphiphiles containing ester or ether-linked lipophilic groups
  申请人：Genzyme Corporation

  公开号：US05840710A1

  公开（公告）日：1998-11-24

  Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

  提供了一种新型的阳离子两性分子，有助于将生物活性（治疗性）分子输送到细胞内。这些两性分子包含从类固醇、单或双烷胺基或烷基或酰基团衍生的亲脂基团；以及从胺、烷胺或多烷基胺衍生的在生理pH下可质子化的阳离子基团。还提供了通常通过将一个或多个阳离子两性分子的分散液与治疗分子接触而制备的治疗组合物。根据本发明的实践，可以将可输送到细胞内的治疗分子包括DNA、RNA和多肽。本发明的治疗组合物的代表性用途包括提供基因治疗，以及将反义多核苷酸或生物活性多肽输送到细胞中。关于用于基因治疗的治疗组合物，DNA通常以质粒的形式提供，以与阳离子两性分子结合。还公开了新型且高效的质粒构建物，包括那些在为临床炎症并发症复杂的情况下提供基因治疗方面特别有效的构建物。此外，描述了通过静脉给药治疗组合物来定位器官进行基因治疗的方法。
• Cationic amphiphiles containing dialkylamine lipophilic groups for
  申请人：Genzyme Corporation

  公开号：US05719131A1

  公开（公告）日：1998-02-17

  Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

  提供了一种新型的阳离子两性分子，有助于将生物活性（治疗性）分子输送到细胞内。这些两性分子包含从类固醇、单或双烷胺基或烷基或酰基团衍生的亲脂基团；以及从胺、烷胺或多烷胺衍生、在生理pH下可质子化的阳离子基团。还提供了通常通过将一个或多个阳离子两性分子的分散液与治疗分子接触而制备的治疗组合物。根据本发明的实践，可以将可输送到细胞内的治疗分子包括DNA、RNA和多肽。本发明的治疗组合物的代表性用途包括提供基因治疗，以及将反义多核苷酸或生物活性多肽输送到细胞中。关于用于基因治疗的治疗组合物，DNA通常以质粒的形式提供，用于与阳离子两性分子结合。还公开了新型且高效的质粒构建物，包括那些在为临床炎症并发症复杂的情况下提供基因治疗方面特别有效的构建物。此外，还描述了通过静脉给药治疗组合物来定位器官进行基因治疗的方法。
• Cationic amphiphile compositions for intracellular delivery of
  申请人：Genzyme Corporation

  公开号：US05939401A1

  公开（公告）日：1999-08-17

  Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. By this invention, such cationic amphiphile is used in a state in which it is capable of accepting additional protons, i.e., it is not fully protonated. For purposes of this invention, cationic amphiphiles may be considered to encompass four general categories: (A) T-shaped/steroid-based amphiphiles; (B) T-shaped/non steroid-based amphiphiles; (C) non T-shaped/steroid based amphiphiles and (D) non T-shaped/non steroid-based amphiphiles.

  提供了一种新型阳离子两性分子，可促进生物活性（治疗性）分子进入细胞。通过这一发明，这种阳离子两性分子在能够接受额外质子的状态下使用，即未完全质子化。根据本发明的目的，阳离子两性分子可被认为包括四个一般类别：（A）T形/类固醇基两性分子；（B）T形/非类固醇基两性分子；（C）非T形/类固醇基两性分子和（D）非T形/非类固醇基两性分子。
• Cationic amphiphiles containing amino acid or dervatized amino acid
  申请人：Genzyme Corporation

  公开号：US05767099A1

  公开（公告）日：1998-06-16

  Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

  提供了一种新型的阳离子两性分子，有助于将生物活性（治疗性）分子输送到细胞内。这些两性分子包含从类固醇、单或双烷胺基或烷基或酰基团衍生的亲脂基团；以及从胺、烷胺或多烷基胺衍生、在生理pH下可质子化的阳离子基团。还提供了通常通过将一个或多个阳离子两性分子的分散液与治疗分子接触而制备的治疗组合物。根据本发明的实践，可以将DNA、RNA和多肽等治疗分子输送到细胞内。本发明的治疗组合物的代表性用途包括提供基因治疗，以及将反义多核苷酸或生物活性多肽输送到细胞中。关于用于基因治疗的治疗组合物，DNA通常以质粒的形式提供，用于与阳离子两性分子结合。还公开了新型且高效的质粒构建物，包括那些在为临床炎症并发症复杂的情况提供基因治疗方面特别有效的构建物。此外，描述了通过静脉给药治疗组合物来实现基因治疗的器官靶向。
• CATIONIC AMPHIPILE COMPOSITIONS FOR INTERACELLUAR DELIVERY OF THERAPEUTIC MOLECULES
  申请人：——

  公开号：US20020013282A1

  公开（公告）日：2002-01-31

  Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. By this invention, such cationic amphiphile is used in a state in which it is capable of accepting additional protons, i.e., it is not fully protonated. For purposes of this invention, cationic amphiphiles may be considered to encompass four general categories: (A) T-shaped/steroid-based amphiphiles; (B) T-shaped/non steroid-based amphiphiles; (C) non T-shaped/steroid based amphiphiles and (D) non T-shaped/non steroid-based amphiphiles.

  提供了新型阳离子两性分子，可促进生物活性（治疗）分子进入细胞。通过这项发明，这种阳离子两性分子在能够接受额外质子的状态下使用，即它没有完全质子化。为了这项发明的目的，阳离子两性分子可以被认为包括四个一般类别：（A）T形/类固醇基两性分子；（B）T形/非类固醇基两性分子；（C）非T形/类固醇基两性分子和（D）非T形/非类固醇基两性分子。