[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(pyridin-2-yldisulfanyl)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 1032314-11-6

• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(pyridin-2-yldisulfanyl)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 1032314-11-6
• 化学式: C₅₆H₆₀N₂O₁₅S₂
• 分子量: 1065.23
• InChiKey: CRXUKGYMHINRLG-PQXCICESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  75
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  291
• 氢给体数：
  3
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  Ac-D-Cys-(D-Arg)8-NH2*8TFA 、 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(pyridin-2-yldisulfanyl)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 以 N,N-二甲基甲酰胺 为溶剂， 以63%的产率得到
  参考文献：
  名称：

  WO2008/69824

  摘要：

  公开号：
• 作为产物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(pyridin-2-yldisulfanyl)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 氟化氢吡啶 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[4-(pyridin-2-yldisulfanyl)butanoyloxy]-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  WO2008/69824

  摘要：

  公开号：

文献信息

• COMPOSITIONS AND METHODS FOR TRANSPORT OF MOLECULES WITH ENHANCED RELEASE PROPERTIES ACROSS BIOLOGICAL BARRIERS
  申请人：Wender Paul A

  公开号：US20100255499A1

  公开（公告）日：2010-10-07

  Conjugates of a cargo molecule with a transporter molecule are disclosed, where the cargo molecule and the transporter molecule are linked covalently by a releasable linker. The cargo of the conjugate can be a biologically active agent or a reporter molecule. The transporter modulates the transport of the cargo across a biological barrier (e.g., a cell membrane) compared to the transport of the unconjugated cargo. Releasable linkers suitable for rapid and facile conjugation to various types of cargo and transporters are also disclosed, along with methods for using the linkers in the synthesis of conjugates.

  本发明公开了一种货物分子与运输蛋白分子的共轭体，其中货物分子和运输蛋白分子通过可释放的连接剂共价连接。共轭体的货物可以是生物活性剂或报告分子。与未共轭货物的运输相比，运输蛋白调节货物通过生物屏障（例如细胞膜）的运输。还公开了适用于快速和容易地与各种类型的货物和运输蛋白共轭的可释放连接剂，以及使用连接剂合成共轭体的方法。
• Conjungation of Small Molecules to Octaarginine Transporters for Overcoming Multi-Drug Resistance
  申请人：Wender Paul

  公开号：US20110160146A1

  公开（公告）日：2011-06-30

  Many cancer therapeutic agents elicit resistance that renders them ineffective and often produces cross resistance to other drugs. One of the most common mechanisms of resistance involves P-glycoprotein (Pgp) mediated drug efflux. Here we provide compositions and methods that restore the efficacy of a therapeutic agent reduced by resistance by conjugation of the same agent to an oligoarginine transporter comprising from about 5 to about 25 guanidino or amidino moieties. We specifically show that the widely used chemotherapeutic agent taxol, ineffective against taxol-resistant human ovarian cancer cell lines, can be incorporated into an octaarginine conjugate that is effective against the same taxol-resistant cell lines. Significantly, the ability of the taxol conjugates to overcome taxol resistance is observed both in cell culture and in animal models of ovarian cancer. The generality and mechanistic basis for this effect were also explored with other Pgp substrate. This approach shows generality for overcoming the multidrug resistance elicited by small molecule cancer chemotherapeutics and could improve the prognosis for many cancer patients and fundamentally alter search strategies for novel therapeutic agents effective against resistant disease.
• [EN] CONJUGATION OF SMALL MOLECULES TO OCTAARGININE TRANSPORTERS FOR OVERCOMING MULTI-DRUG RESISTANCE<br/>[FR] CONJUGAISON DE PETITES MOLÉCULES À DES TRANSPORTEURS DE L'OCTA-ARGININE POUR SURMONTER LA RÉSISTANCE À DE MULTIPLES MÉDICAMENTS ET AMÉLIORER L'EFFICACITÉ ET LA SOLUBILITÉ
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2009099636A1

  公开（公告）日：2009-08-13

  Many cancer therapeutic agents elicit resistance that renders them ineffective and often produces cross resistance to other drugs. One of the most common mechanisms of resistance involves P-glycoprotein (Pgp) mediated drug efflux. Here we provide compositions and methods that restore the efficacy of a therapeutic agent reduced by resistance by conjugation of the same agent to an oligoarginine transporter comprising from about 5 to about 25 guanidino or amidino moieties. We specifically show that the widely used chemotherapeutic agent taxol, ineffective against taxol-resistant human ovarian cancer cell lines, can be incorporated into an octaarginine conjugate that is effective against the same taxol-resistant cell lines. Significantly, the ability of the taxol conjugates to overcome taxol resistance is observed both in cell culture and in animal models of ovarian cancer. The generality and mechanistic basis for this effect were also explored with other Pgp substrate. This approach shows generality for overcoming the multidrug resistance elicited by small molecule cancer chemotherapeutics and could improve the prognosis for many cancer patients and fundamentally alter search strategies for novel therapeutic agents effective against resistant disease.