2'-O-(methoxyacetyl)paclitaxel | 161742-53-6

• 英文名称: 2'-O-(methoxyacetyl)paclitaxel
• 英文别名: 2'-methoxyacetylpaclitaxel；2'-O-(Methoxyacetyl)taxol；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-2-(2-methoxyacetyl)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: 161742-53-6
• 化学式: C₅₀H₅₅NO₁₆
• 分子量: 925.984
• InChiKey: VPFGDLBWWIYETJ-MJZMOBIKSA-N

物化性质

• 沸点：
  974.6±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  67
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  237
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2'-O-(methoxyacetyl)paclitaxel 以 二氯甲烷 、 异丙醇 为溶剂， 反应 17.0h， 生成 Taxol 7-(2-hydroxyethyl)carbamate
  参考文献：
  名称：

  Highly Water Soluble Taxol Derivatives: 7-Polyethylene Glycol Carbamates and Carbonates

  摘要：

  The first examples of highly water soluble taxol derivatives (0.1 mmol/mL) were prepared by the attachment of polyethylene glycol (molecular weight 2-5 kD) at the 7-position of taxol via a methane or carbonate linkage. When lower molecular weight polyethylene glycols (350 and 750) were used, the solubilities were considerably lower (1.87 x 10(-3) mmol/mL) but still substantially greater than taxol itself. Additional 7-substituted taxol derivatives were also prepared by utilizing small molecules consisting of sugars and ionic and multifunctional compounds. However, most of these derivatives had solubilities, calculated from HPLC retention times, that did not differ significantly from taxol itself. The use of methoxyacetate as a protecting group during these syntheses is discussed.

  DOI：

  10.1021/jo00107a010
• 作为产物：
  描述：

  2'-Nvoc-PTX 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 18.0h， 生成 2'-O-(methoxyacetyl)paclitaxel
  参考文献：
  名称：

  Novel photoactivatable paclitaxel derivatives and uses thereof, in particular in cellbiology and cancer treatment

  摘要：

  本发明提供了新型光活性紫杉醇衍生物，其中紫杉醇分子的至少C7位，优选是C2'和C7位均被取代为光解脱基团，例如色团。通常，色团选自包括2-硝基苯基醚、氨甲酰基或碳酸酯及其4,5-二烷氧基取代衍生物；2-硝基苯乙基醚、氨甲酰基或碳酸酯及其4,5-二烷氧基取代衍生物或其p-取代衍生物；α-羧基-2-硝基苯基醚、氨甲酰基或碳酸酯及其4,5-二烷氧基取代衍生物；2(2-硝基苯基)乙基醚、氨甲酰基或碳酸酯及其4,5-二烷氧基取代衍生物；香豆素-4-甲基醚或碳酸酯及其7-烷氧基、6,7-二烷氧基、6-溴-7-烷氧基或7-二烷基氨基取代衍生物；p-羟基苯乙酰醚或氨甲酰基及其间位取代衍生物或结构相关化合物。更具体地，色团是4,5-二甲氧基-2-硝基苯氧羰基（Nvoc）或结构相关化合物。本发明的进一步方面涉及这些紫杉醇衍生物在生物、医学和制药应用中的使用，特别是在细胞生物学和癌症治疗中。紧密相关的方面是包括上述紫杉醇衍生物的抗肿瘤药物。

  公开号：

  EP2565188A1

文献信息

• Design and synthesis of taxane derivatives of valproic acid as potent and selective cytotoxic agents
  作者：Himaja Malipeddi、Sunil V. Mali、Moonjit Das

  DOI：10.1007/s00044-016-1635-6

  日期：2016.11

  overcoming the drug resistance problem. Valproic acid, a well-known antiepileptic drug is in advanced clinical studies for cancer treatment. In the present study, valproic acid was incorporated into the taxane moiety at various positions and the new analogs were evaluated for their in vitro cytotoxicity. The novel analog, Valprotaxel showed comparable cytotoxicity in head and neck, and colon cancer cell

  对抗癌药的耐药性对癌症化疗具有重要意义。细胞毒性剂化学结构的细微变化可以改变它们的生物学相互作用，这对于克服耐药性问题可能是有益的。丙戊酸是一种著名的抗癫痫药，目前正在癌症的高级临床研究中。在本研究中，丙戊酸在不同位置掺入紫杉烷部分，并评估了新的类似物的体外细胞毒性。与紫杉醇和多西紫杉醇相比，新型类似物丙戊紫杉醇在头颈部和结肠癌细胞系中具有可比的细胞毒性，并且对癌细胞的选择性显着提高。
• Synthesis and Protein Binding of (4-Carboxybutyl)carbamoyl- Substituted Taxoids
  作者：Torsten Blitzke、Alexander Baranovsky、Bernd Schneider

  DOI：10.1002/1522-2675(20010711)84:7<1989::aid-hlca1989>3.0.co;2-m

  日期：2001.7.11

  (4-Carboxybutyl)carbamates 5 and 6, as well as 10, derived from 10-O-deacetylbaccatin III (1) and paclitaxel (2), respectively, were synthesized by reaction of unprotected I and 2 ' -O-(methoxyacetyl)paclitaxel (8), respectively. with trimethylsilyl 5-isocyanatopentanoate in good yields. The carbamoyl-taxoids were conjugated to bovine-scrum albumin and analyzed by MALDI-TOF mass spectrometry.

  (4-羧基丁基)脲衍生物5和6，以及10，分别由10-O-脱乙酰基百草枯 III（1）和紫杉醇（2）合成，通过将未保护的1，以及2'-O-(甲氧基乙酰基)紫杉醇（8），分别与三甲基硅基5-异氰酸根戊酸酯反应，获得良好收率。这些羰氨甲酸紫杉醇类化合物被偶联到牛血清白蛋白，并通过MALDI-TOF质谱进行分析。
• [EN] NOVEL PHOTOACTIVATABLE PACLITAXEL DERIVATIVES AND USES THEREOF, IN PARTICULAR IN CELLBIOLOGY AND CANCER TREATMENT<br/>[FR] NOUVEAUX DÉRIVÉS DE PACLITAXEL PHOTOACTIVABLES ET LEURS UTILISATIONS, NOTAMMENT EN BIOLOGIE CELLULAIRE ET POUR LE TRAITEMENT DU CANCER
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2013029723A1

  公开（公告）日：2013-03-07

  The present invention provides novel photoactivatable paclitaxel derivatives wherein the C2 and C7 positions of the paclitaxel molecule are substituted with a photocleavable moiety such as a chromophore. Typically, the chromophore is selected from the group comprising 2-nitrobenzyl ethers, carbamates or carbonates and their 4,5-dialkoxy substituted variants; 2-nitrophenylethyl ethers, carbamates or carbonates and their 4,5-dialkoxy substituted variants, or their p-substituted derivatives; oc-carboxy-2-nitrobenzyl ethers, carbamates or carbonates and their 4,5-dialkoxy substituted variants; 2(2-nitro- phenyl) ethyl ethers, carbamates or carbonates and their 4,5-dialkoxy substituted variants; coumarin-4-ylmethyl ethers, or carbonates and their 7-alkoxy, 6, 7-dialkoxy, 6-bromo-7-alkoxy or 7-dialkylamino substituted variants; p-hydroxyphenacyl ethers or carbamates and their meta-substituted derivatives or structurally related compounds. More specifically, the chromophore is 4, 5-dimethoxy-2- nitrobenyloxycarbonyl (Nvoc) or a structurally related compound. Further aspects of the invention relate to the use of these paclitaxel derivatives in biological, medical and pharmaceutical applications, in particular in cellbiology and cancer treatment. A closely related aspect is an antitumor medicament comprising the above paclitaxel derivatives.

  本发明提供了新型光致活化紫杉醇衍生物，其中紫杉醇分子的C2和C7位置被光解脱基团（例如色团）所取代。通常，色团被选自包括2-硝基苯醚、氨基甲酸酯或碳酸酯及其4,5-二烷氧基取代衍生物；2-硝基苯乙醚、氨基甲酸酯或碳酸酯及其4,5-二烷氧基取代衍生物或其p-取代衍生物；oc-羧基-2-硝基苯醚、氨基甲酸酯或碳酸酯及其4,5-二烷氧基取代衍生物；2（2-硝基苯基）乙醚、氨基甲酸酯或碳酸酯及其4,5-二烷氧基取代衍生物；香豆素-4-基甲醚或碳酸酯及其7-烷氧基、6,7-二烷氧基、6-溴-7-烷氧基或7-二烷基氨基取代衍生物；p-羟基苯乙醚或氨基甲酸酯及其间位取代衍生物或结构相关化合物。更具体地，色团是4,5-二甲氧基-2-硝基苯氧羰基（Nvoc）或其结构相关化合物。该发明的进一步方面涉及这些紫杉醇衍生物在生物、医学和制药应用中的使用，特别是在细胞生物学和癌症治疗中。与此密切相关的方面是包括上述紫杉醇衍生物的抗肿瘤药物。
• Synthesis and biological activity of conjugates between paclitaxel and the cell delivery vector penetratin
  作者：Shudong Wang、Nikolai Z. Zhelev、Susan Duff、Peter M. Fischer

  DOI：10.1016/j.bmcl.2006.02.035

  日期：2006.5

  Synthesis of paclitaxel-penetratin (pAntp) constructs, in which the 2'- or 7-position of paclitaxel was used as the attachment site for linker connecting the drug and peptide moieties, is described. Paclitaxel-2'-pAntp[43-58]-NH2 3b and paclitaxel-2'-pAntp[52-58]-NH2 3c showed excellent antitumour activity against human lung and breast cancer cell lines. These conjugates were highly soluble and stable with a half-life of >8 h under cell culture conditions. The drug-peptide conjugates may be therapeutically useful due to improved pharmaceutical properties. (C) 2006 Elsevier Ltd. All rights reserved.