3'-O-(tert-butoxycarbonyl)gemcitabine | 250698-51-2

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3'-O-(tert-butoxycarbonyl)gemcitabine
• 英文别名: (2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl tert-butyl carbonate；3’-O-(tert-butoxycarbonyl)-gemcitabine；[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-2-(hydroxymethyl)oxolan-3-yl] tert-butyl carbonate
• CAS: 250698-51-2
• 化学式: C₁₄H₁₉F₂N₃O₆
• 分子量: 363.318
• InChiKey: LKIFGKNBZDGLOI-SZEHBUNVSA-N

物化性质

• 沸点：
  517.5±60.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-O-(tert-butoxycarbonyl)gemcitabine 在 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 113.0h， 生成 2'-2'-difluoro-deoxycytidine-5'-octadecylphosphate
  参考文献：
  名称：

  LIPOPHILIC MONOPHOSPHORYLATED DERIVATIVES AND NANOPARTICLES

  摘要：

  其中提供了伊立替宾的亲脂性单磷酸化衍生物，还提供了包含伊立替宾的亲脂性单磷酸化衍生物的纳米粒子组合物、相应的药物组合物，以及一种治疗癌症或病毒感染的方法，该方法包括给需要的受试者使用本文披露的药物组合物。

  公开号：

  US20130131008A1
• 作为产物：
  描述：

  3',5'-O-bis(tert-butoxycarbonyl)gemcitabine 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 52.0h， 生成 3'-O-(tert-butoxycarbonyl)gemcitabine
  参考文献：
  名称：

  Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)

  摘要：

  Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.

  DOI：

  10.1021/jo9911140

文献信息

• [EN] DIASTEREOSELECTIVE SYNTHESIS OF PHOSPHATE DERIVATIVES AND OF THE GEMCITABINE PRODRUG NUC-1031<br/>[FR] SYNTHÈSE DIASTÉRÉOSÉLECTIVE DE DÉRIVÉS DE PHOSPHATE ET DU PROMÉDICAMENT DE GEMCITABINE NUC-1031
  申请人：NUCANA BIOMED LTD

  公开号：WO2017098252A1

  公开（公告）日：2017-06-15

  The present invention provides a method for the preparation of intermediates useful in the synthesis of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. It also provides a method of preparing gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate.

  本发明提供了一种用于合成吉西他滨-[苯基苯氧基-L-丙氨酰)]-磷酸盐中间体的制备方法。它还提供了一种制备吉西他滨-[苯基苯氧基-L-丙氨酰)]-磷酸盐的方法。
• Preparation Method of Nucleoside Phosphoramidate Prodrugs and Intermediates Thereof
  申请人：BrightGene Bio-Medical Technology Co., Ltd.

  公开号：US20180237466A1

  公开（公告）日：2018-08-23

  Provided in the present disclosure are a novel preparation method of nucleoside phosphoramidate prodrugs and the intermediates thereof. In particular, the method is adopted to perform isomer separation on the reaction product from a first step and then perform a two-step chemical synthesis, so as to prepare a high-purity compound S p -1. The method has simple and convenient operation and low cost. The prepared resulting single isomer S p -1 has high purity, and the HPLC purity thereof is 95% or more, and further, 99% or more. The method is suitable for industrial production and can satisfy the need of clinical study. Further, also provided in the present disclosure are a key intermediate phosphorus reagent for preparing the high-purity compound S p -1 and the preparation method thereof.

  本公开提供了一种新颖的核苷酸磷酰胺酯前药及其中间体的制备方法。具体而言，该方法被采用用于对第一步的反应产物进行异构体分离，然后进行两步化学合成，以制备高纯度化合物S p -1。该方法操作简单方便，成本低廉。制备得到的单一异构体S p -1具有高纯度，其HPLC纯度为95%或更高，进一步可达99%或更高。该方法适用于工业生产，并能满足临床研究的需求。此外，本公开还提供了用于制备高纯度化合物S p -1及其制备方法的关键中间体磷试剂。
• Design, characterization, and in vitro antiproliferative efficacy of gemcitabine conjugates based on carboxymethyl glucan
  作者：Lu Ma、Yuancai Chen、Xude Wang、Mingzhou Xiong、Yuanyuan Sun、Xiaoshu Zhang、Yuqing Zhao

  DOI：10.1016/j.bmcl.2018.07.014

  日期：2018.9

  5.5) mimicking the acidic tumor microenvironment. Moreover, A549, HeLa and Caco-2 cancer cell lines were used to evaluate the in vitro cytotoxicity of conjugates and the results showed that binding GEM to CMG significantly enhanced antiproliferative activity of GEM on A549 cells. Therefore, these conjugates may be potentially useful as a delivery vehicle in cancer therapy and worthy of further study

  吉西他滨（GEM）在临床实践中广泛用于治疗癌症和其他几种实体瘤。尽管如此，GEM的抗肿瘤作用仍受到某些限制的部分阻止，这些限制包括半衰期短和缺乏肿瘤定位。羧甲基葡聚糖（CMG）是β-（1-3）-葡聚糖的羧甲基化衍生物，具有生物相容性和生物降解性，并具有潜在的抗癌作用。为了增强的抗增殖活性GEM，四个水溶性轭合物GEM经由多样结合至CMG氨基酸接头设计并合成。1个使用1 H NMR，FT IR，元素分析和RP-HPLC色谱法验证结合物的正确实现。体外释放研究表明，缀合物在生理缓冲液（pH 7.4）中的释放要比模仿酸性肿瘤微环境的酸性缓冲液（pH 5.5）的释放慢。此外，使用A549，HeLa和Caco-2癌细胞系评估缀合物的体外细胞毒性，结果表明，将GEM与CMG结合可显着增强GEM对A549细胞的抗增殖活性。因此，这些缀合物可能潜在地用作癌症治疗中的递送载体，并且值得进一步研究其体内外的结
• Phosphoramidate Compound and Preparation Method and Crystal Thereof
  申请人：BrightGene Bio-Medical Technology Co., Ltd.

  公开号：US20180244701A1

  公开（公告）日：2018-08-30

  The present disclosure involves a composition enriched in compound 61501b, wherein the compound 61501b has a purity of not less than 90% or more. The composition has a significant advantage in preparing a high-purity compound Sp-1. In addition, the present disclosure also provides a preparation method of the composition enriched in compound 61501b. The method adopts a crystallization technique to perform separation and purification, has a simple and convenient operation and good reproducibility, and therefore the compound 61501b in the prepared composition has high purity and quality. Further, the present disclosure also involves a novel crystal form of compound 61501b.

  本公开涉及一种富含61501b化合物的组合物，其中61501b化合物的纯度不低于90%。该组合物在制备高纯度化合物Sp-1方面具有显著优势。此外，本公开还提供了一种富含61501b化合物的组合物的制备方法。该方法采用结晶技术进行分离和纯化，操作简便方便，具有良好的可重复性，因此制备的组合物中的61501b化合物具有高纯度和质量。此外，本公开还涉及61501b化合物的一种新型晶型。
• [EN] SONODYNAMIC THERAPY<br/>[FR] THÉRAPIE SONODYNAMIQUE
  申请人：CALLAN JOHN

  公开号：WO2020249953A1

  公开（公告）日：2020-12-17

  The invention provides a method of preparing a microbubble covalently attached to at least one therapeutic agent which comprises: (i) providing a lipid (e.g. a phospholipid) capable of forming a microbubble; covalently linking at least one therapeutic agent to said lipid to produce a functionalised lipid; and preparing a microbubble from said functionalised lipid. Microbubble-therapeutic agent complexes which comprise a microbubble shell formed from a plurality of lipids (e.g. phospholipids) in which at least a proportion of the lipids are covalently linked to at least one therapeutic agent are also provided. Examples of therapeutic agents which may be attached to the microbubble include chemotherapeutic agents and sonosensitising agents. The complexes find use in methods of sonodynamic therapy and, in particular, in methods of combined sonodynamic therapy and chemotherapy.

  该发明提供了一种制备与至少一种治疗剂共价连接的微泡的方法，该方法包括：提供一种能够形成微泡的脂质（例如磷脂）；将至少一种治疗剂共价连接到所述脂质以产生功能化脂质；以及从所述功能化脂质制备微泡。还提供了包含由多个脂质（例如磷脂）形成的微泡壳的微泡-治疗剂复合物，其中至少一部分脂质共价连接到至少一种治疗剂。可能连接到微泡的治疗剂的例子包括化疗药物和声敏化剂。这些复合物在声动力治疗方法中找到了用途，特别是在结合声动力治疗和化疗的方法中。