14-iodo-N-(trifluoroacetyl)daunorubicin | 26295-55-6

• 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-iodo-N-(trifluoroacetyl)daunorubicin
• 英文别名: N-(trifluoroacetyl)-14-iododaunorubicin；2,2,2-trifluoro-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-iodoacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]acetamide
• CAS: 26295-55-6
• 化学式: C₂₉H₂₇F₃INO₁₁
• 分子量: 749.433
• InChiKey: XPJJRAZAOFSLBD-XUKKXQNXSA-N

物化性质

• 沸点：
  855.0±65.0 °C(Predicted)
• 密度：
  1.84±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  45
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  189
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  14-iodo-N-(trifluoroacetyl)daunorubicin 在 potassium carbonate 、 苯硫酚 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以100%的产率得到三氟乙酰基柔红霉素
  参考文献：
  名称：

  Reaction of halomethyl ketones with thiols and selenols: substitution vs. reduction

  摘要：

  DOI：

  10.1021/jo00325a038

文献信息

• Adriamycin analogues. Preparation and biological evaluation of some N-(trifluoroacetyl)-14-O-[N-acetylamino)acyl]adriamycin derivatives
  作者：Mervyn Israel、David Taube、Ramakrishnan Seshadri、John M. Idriss

  DOI：10.1021/jm00157a026

  日期：1986.7

  structure-activity studies related to the novel DNA-nonbinding adriamycin analogues N-(trifluoroacetyl)adriamycin 14-valerate (AD 32) and N-(trifluoroacetyl)adriamycin 14-O-hemiadipate (AD 143), we have now prepared a series of N-(trifluoroacetyl)adriamycin derivatives with N-acylamino acid esters at the 14-carbinol position. Target compounds were made by reaction of N-(trifluoroacetyl)-14-iododaunorubicin

  与与新型DNA非结合性阿霉素类似物N-（三氟乙酰基）阿霉素14-戊酸酯（AD 32）和N-（三氟乙酰基）阿霉素14-O-二甲双胍（AD 143）有关的结构活性研究相关，我们现在准备了一系列的N-（三氟乙酰基）阿霉素衍生物，在14-甲醇位置带有N-酰基氨基酸酯。通常在二甲基甲酰胺-乙二醇溶剂中，使N-（三氟乙酰基）-14-碘柔红霉素与N-酰基氨基酸的钠盐反应，制得目标化合物。在鼠P388白血病系统中，评估了产品的体外生长抑制活性，并在一定程度上评估了体内抗肿瘤活性。相对于培养的CCRF-CEM细胞，目标化合物的ID 50值通常在与上述DNA非结合性阿霉素类似物的ID 50值相同的范围内。在测试的四种具有体内活性的化合物中，虽然没有一种能像N-（三氟乙酰基）阿霉素14-戊酸酯一样有效，但它们在P388分析系统中均显示出显着的活性，其中三种化合物在所用剂量下基本上具有同等活性最佳剂量的阿霉素。在
• Synthesis of Novel Spin Labeled Analogues of<i>N</i>-(Trifluoroacetyl)Daunorubicin
  作者：Shao-Jun Xu、Cheng Ma、Yan-Guang Wang、Yao-Zu Chen

  DOI：10.1080/00397910008086879

  日期：2000.7

  Three novel spin labeled N-(trifluoroacetyl) daunorubicins 6-8 have been synthesized under mild reaction condition in good yields. The antitumor activity of compound 6 and 8 were evaluated in vitro.
• Adriamycin analogs. Rationale, synthesis, and preliminary antitumor evaluation of highly active DNA-nonbinding N-(trifluoroacetyl)adriamycin 14-O-hemiester derivatives
  作者：Mervyn Israel、P. Gopalakrishnan Potti、Ramakrishnan Seshadri

  DOI：10.1021/jm00147a017

  日期：1985.9

  N-(Trifluoroacetyl)adriamycin 14-valerate (AD 32), a novel DNA nonbinding analogue of adriamycin with superior experimental antitumor activity, has undergone extensive clinical trial, with documentation of antitumor activity and low toxicity in human subjects. However, poor water solubility necessitates that the drug be administered to patients by continuous intravenous infusion at high dilution in a surfactant-containing formulation, with steroid prophylaxis to protect against a chest pain syndrome associated with the vehicle. On the basis of pharmacologic considerations, the title compounds have been prepared as second-generation analogues of N-(trifluoroacetyl)adriamycin 14-valerate with improved aqueous solubility; use is made of the available carboxylic acid function to solubilize the products in dilute aqueous alkaline medium. Target compounds were made by treating N-(trifluoroacetyl)-14-halodaunorubicin (bromo or iodo) with monosodium salts of dibasic acids (malonic, succinic, glutaric, adipic, pimelic, azelaic, sebacic) in aqueous acetone. All of the products showed significant in vivo antitumor activity against the murine P388 leukemia (ip tumor, ip treatment once daily on days 1, 2, 3, and 4); most compounds were superior to the +181% increase in life span afforded by adriamycin (optimal dose 3.0 mg/kg per day), one of two drugs used as positive controls for the assays. Several of the test compounds showed highly curative activity in this system, similar to N-(trifluoroacetyl)adriamycin 14-valerate, the other positive control agent. The hemiadipate product exhibited the most desirable properties of high antitumor efficacy (86% cure rate all P388 tumor-bearing animals through four levels of a 40-70 mg/kg dose-response range), aqueous solubility (60 mg/mL in pH 7.4 phosphate buffer), and solution stability (no decomposition at 4 degrees C, 0.5% hydrolysis at 27 degrees C, over 24 h at pH 7.4).