14-[(N-Hexadecylamido)Succinyl]Doxorubicin | 1357161-18-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: 14-[(N-Hexadecylamido)Succinyl]Doxorubicin
• 英文别名: [2-[(2S,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-oxoethyl] 4-(hexadecylamino)-4-oxobutanoate
• CAS: 1357161-18-2
• 化学式: C₄₇H₆₆N₂O₁₃
• 分子量: 867.047
• InChiKey: BMJNBZCRUMBAOG-UCLRVSCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  62
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  241
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  [2-[(2S,4S)-4-[(2R,4S,5S,6S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-oxoethyl] 4-(hexadecylamino)-4-oxobutanoate 在 哌啶 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 反应 0.17h， 以38 mg的产率得到14-[(N-Hexadecylamido)Succinyl]Doxorubicin
  参考文献：
  名称：

  Synthesis, Anticancer Activities, and Cellular Uptake Studies of Lipophilic Derivatives of Doxorubicin Succinate

  摘要：

  A number of lipophilic 14-substituted derivatives of doxorubicin were synthesized through conjugation of doxorubicin-14-hemisuccinate with different fatty amines or tetradecanol to enhance the lipophilicity, cellular uptake, and cellular retention for sustained anticancer activity. The conjugates inhibited the cell proliferation of human leukemia (CCRF-CEM, 69-76%), colon adenocarcinoma (HT-29, 60-77%), and breast adenocarcinoma (MDA-MB-361, 66-71%) cells at a concentration of 1 mu M after 96-120 h of incubation. The N-tetradecylamido derivative of doxorubicin 14-succinate (10) exhibited consistently comparable antiproliferative activity to doxorubicin in a time-dependent manner (IC50 = 77 nM in CCRF-CEM cells). Flow cytometry analysis showed a 3-fold more cellular uptake of 10 than doxorubicin in SK-OV-3 cells. Confocal microscopy revealed that the conjugate was distributed in cytoplasmic and perinuclear areas during the first 1 h of incubation and slowly relocalized in the nucleus after 24 h. The cellular hydrolysis study showed that 98% of compound 10 was hydrolyzed intracellularly within 48 h and released doxorubicin.

  DOI：

  10.1021/jm201653u