2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethyl 2-acetyloxybenzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethyl 2-acetyloxybenzoate
• 英文别名: 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl 2-acetyloxybenzoate
• 化学式: C₁₇H₂₄O₈
• 分子量: 356.373
• InChiKey: HAADJVKQEDTPJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  25
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethyl 2-acetyloxybenzoate 、 对硝基苯基氯甲酸酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Synthesis of novel SN38-aspirin prodrugs for the treatment of hepatocellular carcinoma

  摘要：

  肝细胞癌（HCC）是最常见的原发性肝脏恶性肿瘤，也是全球癌症相关死亡的主要原因之一。然而，目前没有有效的化疗治疗HCC的方法，其预后仍较差。因此，迫切需要找到一种高效的抗肿瘤药物来治疗HCC。在本研究中，我们将7-乙基-10-羟基喜树碱（SN38），一种抗癌药物伊立替康（CPT-11）的活性代谢物，其活性比CPT-11高出100-1000倍，与阿司匹林结合形成了4种前药。我们通过$^{1}$H NMR和元素分析表征了它们的结构。并在体外评估了这些化合物对两种人肝细胞癌细胞系（BEL-7404和HepG2）的抗癌活性及初步作用机制。我们的数据显示，这些化合物以浓度和时间依赖性方式降低了癌细胞系的存活率。其中，化合物4b显著抑制了HepG2细胞的存活率（IC$_{50}$ = 0.1208 $\mu $M），相比于CPT-11（IC$_{50}$ = 18.4267 $\mu $M）。此外，化合物4b在体外抑制了HepG2细胞的迁移和侵袭。这些发现表明，化合物4b可能作为对抗HCC的有前景的抗癌药物。

  DOI：

  10.3906/kim-1801-21
• 作为产物：
  描述：

  邻乙酰水杨酰氯 在 三乙基硅烷 、 三氟化硼乙醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.25h， 生成 2-[2-[2-(2-Hydroxyethoxy)ethoxy]ethoxy]ethyl 2-acetyloxybenzoate
  参考文献：
  名称：

  A new, vasoactive hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety

  摘要：

  Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose, prophylactic use of acetylsalicylic acid (ASA), an inhibitor of platelet aggregation. To avoid the gastrointestinal damage, ASA prodrugs bearing nitric oxide (NO)-donating moiety covalently conjugated to ASA have been synthesized and evaluated extensively worldwide. Herein the synthesis of a new hybrid ASA ester covalently attached to the NO donor linsidomine, an active metabolite of molsidomine (MOL) is reported. Cell viability assay and hemolysis tests were performed in H9c2 cells and rat erythrocytes, respectively. Our new compound, the ERJ-500 not affected negatively the viability of living cells in the concentration range of 100 nM to 100 mu M. Using the ex vivo Langendorff method on hearts originated from female rats, compound ERJ-500 displayed a dose-dependent, outwashable vasodilative effect in coronary arteries. Vasodilation was observed on isolated working heart model as well, with elevated stroke volume in hearts treated with ERJ-500. Furthermore, a decreased infarct size was also noticed in ERJ-500 treated hearts after ischemia/reperfusion. Based on these observations it can be expected that our new hybrid ASA may contribute to new pharmacological tool in the therapy of ischemic heart conditions and associated syndromes.

  DOI：

  10.1016/j.ejps.2019.02.020

文献信息

• Synthesis of novel SN38-aspirin prodrugs for the treatment of hepatocellular carcinoma
  作者：Chen, Zhimin、Luo, Yi、Fang, Aiping、Fan, Chen、Zeng, Chenjuan

  DOI：10.3906/kim-1801-21

  日期：——

  Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. However, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Consequently, it is urgent to find an efficient antitumor agent to treat HCC. In this study, 7-ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100-1000 times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs. Their structures were characterized by $^1}$H~NMR and elemental analysis. The in vitro anticancer activities of these compounds on two human hepatocellular carcinoma cell lines (BEL-7404 and HepG2) and preliminary mechanisms of action were explored. Our data indicated that these compounds decreased the viability of cancer cell lines in a concentration- and time-dependent manner. Among them, compound 4b significantly inhibited cell viability of HepG2 cells (IC$_50\, }$= 0.1208 $\mu $M) when compared with CPT-11 (IC$_50}$ = 18.4267 $\mu $M). Furthermore, compound 4b blocked HepG2 cell migration and invasion in vitro. These findings suggest that compound 4b may be used as a promising anticancer agent against HCC.

  肝细胞癌（HCC）是最常见的原发性肝脏恶性肿瘤，也是全球癌症相关死亡的主要原因之一。然而，目前没有有效的化疗治疗HCC的方法，其预后仍较差。因此，迫切需要找到一种高效的抗肿瘤药物来治疗HCC。在本研究中，我们将7-乙基-10-羟基喜树碱（SN38），一种抗癌药物伊立替康（CPT-11）的活性代谢物，其活性比CPT-11高出100-1000倍，与阿司匹林结合形成了4种前药。我们通过$^1}$H NMR和元素分析表征了它们的结构。并在体外评估了这些化合物对两种人肝细胞癌细胞系（BEL-7404和HepG2）的抗癌活性及初步作用机制。我们的数据显示，这些化合物以浓度和时间依赖性方式降低了癌细胞系的存活率。其中，化合物4b显著抑制了HepG2细胞的存活率（IC$_50}$ = 0.1208 $\mu $M），相比于CPT-11（IC$_50}$ = 18.4267 $\mu $M）。此外，化合物4b在体外抑制了HepG2细胞的迁移和侵袭。这些发现表明，化合物4b可能作为对抗HCC的有前景的抗癌药物。
• A new, vasoactive hybrid aspirin containing nitrogen monoxide-releasing molsidomine moiety
  作者：Kitti Szőke、Attila Czompa、István Lekli、Péter Szabados-Fürjesi、Mihály Herczeg、Magdolna Csávás、Anikó Borbás、Pál Herczegh、Árpád Tósaki

  DOI：10.1016/j.ejps.2019.02.020

  日期：2019.4

  Ischemic heart conditions are among the main causes of sudden cardiac death worldwide. One of the strategies for avoiding myocardial infarction is the low-dose, prophylactic use of acetylsalicylic acid (ASA), an inhibitor of platelet aggregation. To avoid the gastrointestinal damage, ASA prodrugs bearing nitric oxide (NO)-donating moiety covalently conjugated to ASA have been synthesized and evaluated extensively worldwide. Herein the synthesis of a new hybrid ASA ester covalently attached to the NO donor linsidomine, an active metabolite of molsidomine (MOL) is reported. Cell viability assay and hemolysis tests were performed in H9c2 cells and rat erythrocytes, respectively. Our new compound, the ERJ-500 not affected negatively the viability of living cells in the concentration range of 100 nM to 100 mu M. Using the ex vivo Langendorff method on hearts originated from female rats, compound ERJ-500 displayed a dose-dependent, outwashable vasodilative effect in coronary arteries. Vasodilation was observed on isolated working heart model as well, with elevated stroke volume in hearts treated with ERJ-500. Furthermore, a decreased infarct size was also noticed in ERJ-500 treated hearts after ischemia/reperfusion. Based on these observations it can be expected that our new hybrid ASA may contribute to new pharmacological tool in the therapy of ischemic heart conditions and associated syndromes.