2'-t-BOC-glycyltaxol | 117527-53-4

• 英文名称: 2'-t-BOC-glycyltaxol
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]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
• CAS: 117527-53-4
• 化学式: C₅₄H₆₂N₂O₁₇
• 分子量: 1011.09
• InChiKey: YLJLYOWERIMEHJ-YQLQIUCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  73.0
• 可旋转键数：
  13.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  265.69
• 氢给体数：
  4.0
• 氢受体数：
  17.0

反应信息

• 作为产物：
  描述：

  BOC-甘氨酸 、 紫杉醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 生成 2'-t-BOC-glycyltaxol
  参考文献：
  名称：

  XlogP和Hansen溶解度参数对小分子修饰的紫杉醇抗癌药物共轭物自组装成纳米颗粒的影响

  摘要：

  小分子修饰的抗癌药物偶联物（SMMDC）可以自组装成纳米颗粒（NP），作为用于癌症治疗的治疗性NP平台。在这里，我们证明了紫杉醇（PTX）SMMDC的XlogP和Hansen溶解度参数对于SMMDC自组装成NP至关重要。PTX SMMDC的非晶态也将影响SMMDC自组装为NP。但是，这些PTX SMMDC NP的抗肿瘤活性与它们的XlogP值一起下降，表明用于设计SMMDC的合适的XlogP值对于自组装成NP和具有抗肿瘤活性很重要。对于更高水平的XlogP SMMDC，在SMMDC的设计中应考虑使用可降解的接头，以克服抗肿瘤活性较低的问题。

  DOI：

  10.1021/acs.bioconjchem.7b00767

文献信息

• Synthesis of congeners and prodrugs. 3. Water-soluble prodrugs of taxol with potent antitumor activity
  作者：H. M. Deutsch、J. A. Glinski、M. Hernandez、R. D. Haugwitz、V. L. Narayanan、M. Suffness、Leon H. Zalkow

  DOI：10.1021/jm00124a011

  日期：1989.4

  Taxol has shown good in vivo antitumor activity in a number of test systems. The formulation of taxol for antitumor testing has been difficult. Esterification at either C-2' or C-7 resulted in loss of in vitro tubulin assembly activity but not cytotoxicity. These observations suggested that esters at C-2' and/or C-7, which would tend to promote water solubility, might serve as useful prodrugs of taxol. The reaction of taxol with either succinic anhydride or glutaric anhydride in pyridine solution at room temperature gave the crystalline mono 2'-adducts 1b and 1f, respectively. Salts of these acids (1b, 1f, 1i) were formed by the addition of 1 equiv of the corresponding base, followed by evaporation and/or freeze-drying of the solvent(s). The salts had improved antitumor activity as compared to the free acids. The triethanolamine and N-methylglucamine salts showed greatly improved aqueous solubility and were more active than the sodium salts. The glutarate series was preferred because of the higher activity and the higher yields obtained. 2'-Glutaryltaxol (1f) was coupled with 3-(dimethylamino)-1-propylamine, using CDI, to form in excellent yield the amino amide 1o. The hydrochloride salt (1p) showed good solubility and was extremely potent and active. At 10 mg/kg, in the B16 screen, 1p gave a T/C of 352 with 5 out of 10 cures. In the MX-1 breast xenograft assay, this prodrug gave values of -100 at doses of 40 and 20 mg/kg, with all live animals being tumor free.