2'-succinyl PTX-phe-phe-arg chloromethyl ketone | 1221127-64-5

• 英文名称: 2'-succinyl PTX-phe-phe-arg chloromethyl ketone
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-[4-[[(2S)-1-[[(2S)-1-[[(3S)-1-chloro-6-(diaminomethylideneamino)-2-oxohexan-3-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoyl]oxy-3-phenylpropanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate;2,2,2-trifluoroacetic acid
• CAS: 1221127-64-5
• 化学式: C₂HF₃O₂*C₇₆H₈₆ClN₇O₁₉
• 分子量: 1551.03
• InChiKey: XWYDPRYUUULMGN-OAXKEBEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  110
• 可旋转键数：
  34
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  433
• 氢给体数：
  9
• 氢受体数：
  25

反应信息

• 作为产物：
  描述：

  、 紫杉醇琥珀酸盐 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以64%的产率得到2'-succinyl PTX-phe-phe-arg chloromethyl ketone
  参考文献：
  名称：

  Targeted Delivery of Paclitaxel to Tumor Cells: Synthesis and in Vitro Evaluation

  摘要：

  We previously reported a novel drug delivery system, drug-linker-Phe-Phe-Arg-methylketone (FFR-mk)-factor VIIa (fVIIa). The method utilizes tissue factor (TF), which is aberrantly and abundantly expressed on many cancer cells. The advantage of this delivery system is its ability to furnish a potent anticancer drug specifically to the tumor vasculature and cancer cells. In this paper, we describe the synthesis of paclitaxel (PTX)-Phe-Phe-Arg-chloromethyl ketone (FFR-ck), followed by coupling with fVIIa to form PTX-FFR-mk-fVIIa. FFRck was separately linked to the OH groups at the C2' or C7 positions of PTX (C2'- or C7-PTX-FFRck), the C2' analogue exhibiting better activity against human head and neck squamous KB 3-1 cells. The activity order against PTX-sensitive KB 3-1 cells is C2'-PTX-FFRmk-fVIIa > PTX > C2'-PTX-FFRck. The C2' complex shows an IC(50) of 12 nM against the PTX-sensitive cell line and 130 nM against PTX-resistant cells.

  DOI：

  10.1021/jm901763f