2'-succinylgemcitabine | 117702-11-1

• 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: 2'-succinylgemcitabine
• 英文别名: 5'-O-(3-Carboxy-1-oxypropyl)-2'-deoxy-2',2'-difluorocytidine；5'-O-(3-carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine；2'-deoxy-2',2'-difluorocytidine-5'-(hydrogen butanedioate)；4-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxy]-4-oxobutanoic acid
• CAS: 117702-11-1
• 化学式: C₁₃H₁₅F₂N₃O₇
• 分子量: 363.275
• InChiKey: YTBOQDUZTPLITF-DIMCTHFVSA-N

物化性质

• 沸点：
  614.233±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.749±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  丁二酸酐 、 盐酸吉西他滨 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2'-succinylgemcitabine
  参考文献：
  名称：

  针对非小细胞肺癌联合治疗的靶向肿瘤的聚合物纳米结构脂质载体，具有精确的比例控制双药物负荷。

  摘要：

  吉西他滨（GEM）和紫杉醇（PTX）是针对非小细胞肺癌（NSCLC）的有效联合抗癌药。目前，联合治疗的主要挑战是控制的精确度，它将最大程度地提高联合治疗的效果。在这里，我们报告了一种新型方法，可将GEM（亲水性）和PTX（疏水性）加载到单纯性肿瘤靶向的纳米结构脂质载体（NLC）中，以精确控制两种药物的比例。我们通过可水解的酯接头将两种药物共价预缀合以形成药物缀合物。N-乙酰基-d-葡萄糖胺（NAG）是靶向葡萄糖受体的配体。我们在NAG-NLC的形成过程中添加了NAG。通常，证明了聚（6-O-甲基丙烯酰基-d-吡喃半乳糖）-GEM / PTX（PMAGP-GEM / PTX）共轭物的合成，NAG-NLCs是通过乳化和溶剂蒸发制备的。NAG-NLC显示出球形，平均直径为120.3±1.3 nm，低多分散指数为0.233±0.04，并且对这两种药物进行精确的比例控制。细胞毒性试验表明，NAG-N

  DOI：

  10.2147/ijn.s121262

文献信息

• Immunoglobulin conjugates
  申请人：Eli Lilly and Company

  公开号：US04994558A1

  公开（公告）日：1991-02-19

  Immunoglobulin conjugates formed by reacting a difluoronucleoside with an immunoglobulin via an alkane dioic acid linking group.

  通过使用一个烷二酸连接基将二氟核苷与免疫球蛋白反应形成的免疫球蛋白偶联物。
• Immunoglobulin conjugates of 2',2'-difluronucleosides
  申请人：Eli Lilly and Company

  公开号：US04814438A1

  公开（公告）日：1989-03-21

  Immunoglobulin conjugates are formed by reacting a difluoronucleoside with an immunoglobulin via an alkane dioic acid linking group.

  免疫球蛋白偶联物是通过将一种二氟核苷与免疫球蛋白通过烷二酸链连接反应而形成的。
• Multitargeting Prodrugs that Release Oxaliplatin, Doxorubicin and Gemcitabine are Potent Inhibitors of Tumor Growth and Effective Inducers of Immunogenic Cell Death
  作者：Amrita Sarkar、Vojtech Novohradsky、Moumita Maji、Tomer Babu、Lenka Markova、Hana Kostrhunova、Jana Kasparkova、Valentina Gandin、Viktor Brabec、Dan Gibson

  DOI：10.1002/anie.202310774

  日期：2023.10.16

  A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent with nM IC_50s; it is highly selective to cancer cells with mean selectivity indices to human (136) and murine (320) cancer cells. It effectively induces release of DAMPs (CALR, ATP & HMGB1) in CT26 cells facilitating more efficient phagocytosis by J774 macrophages than the FDA drugs or their co‐administration. The viability of CT26 cells co‐cultured with J774 macrophages and treated with 2 was reduced by 32 % compared to the non‐treated cells, suggesting a synergistic antiproliferative effect between the chemical and immune reactions. 2 inhibited in vivo tumor growth in two murine models (LLC and CT26) better than the FDA drugs or their co‐administration with significantly lower body weight loss. Mice inoculated with CT26 cells treated with 2 showed slightly better tumor free survival than doxorubicin.

  摘要 一种多靶点原药（2）能以其活性形式在癌细胞中释放吉西他滨、奥沙利铂和多柔比星，是一种有效的细胞毒药物，其 IC50 为 nM；它对癌细胞具有高度选择性，对人（136）和鼠（320）癌细胞具有平均选择性指数。它能有效诱导 CT26 细胞释放 DAMPs（CALR、ATP & 和 HMGB1），从而促进 J774 巨噬细胞更有效地吞噬细胞。与 J774 巨噬细胞共同培养的 CT26 细胞经 2 处理后，其存活率比未处理的细胞降低了 32%，这表明化学反应和免疫反应之间存在协同抗增殖效应。在两种小鼠模型（LLC 和 CT26）中，2 对体内肿瘤生长的抑制效果优于 FDA 药物或它们的联合用药，而且体重下降明显。用 2 处理过的 CT26 细胞接种小鼠的无瘤存活率略高于多柔比星。
• <p>A NAG-Guided Nano-Delivery System for Redox- and pH-Triggered Intracellularly Sequential Drug Release in Cancer Cells</p>
  作者：Yan Liang、Jing Zhang、Baocheng Tian、Zimei Wu、Darren Svirskis、Jingtian Han

  DOI：10.2147/ijn.s226249

  日期：——

  Aim: Sequential treatment with paclitaxel (PTXL) and gemcitabine (GEM) is considered clinically beneficial for non-small-cell lung cancer. This study aimed to investigate the effectiveness of a nano-system capable of sequential release of PTXL and GEM within cancer cells.Methods: PTXL-ss-poly(6-O-methacryloyl-d-galactopyranose)-GEM (PTXL-ss-PMAGP-GEM) was designed by conjugating PMAGP with PTXL via disulfide bonds (-ss-), while GEM via succinic anhydride (PTXL:GEM=1:3). An amphiphilic block copolymer N-acetyl-d-glucosamine(NAG)-poly(styrene-alt-maleic anhydride)(58)-b-polystyrene(130) acted as a targeting moiety and emulsifier in formation of nanostructures (NLCs).Results: The PTXL-ss-PMAGP-GEM/NAG NLCs (119.6 nm) provided a sequential in vitro release of, first PTXL (redox-triggered), then GEM (pH-triggered). The redox- and pH-sensitive NLCs readily distributed homogenously in the cytoplasm. NAG augmented the uptake of NLCs by the cancer cells and tumor accumulation. PTXL-ss-PMAGP-GEM/NAG NLCs exhibited synergistic cytotoxicity in vitro and strongest antitumor effects in tumor-bearing mice compared to NLCs lacking pH/redox sensitivities or free drug combination.Conclusion: This study demonstrated the abilities of PTXL-ss-PMAGP-GEM/NAG NLCs to achieve synergistic antitumor effect by targeted intracellularly sequential drug release.
• US4814438A
  申请人：——

  公开号：US4814438A

  公开（公告）日：1989-03-21