12-thioethyldodecanoic acid | 186093-30-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 12-thioethyldodecanoic acid
• 英文别名: 12-(Ethylthio)dodecanoic acid；12-ethylsulfanyldodecanoic acid
• CAS: 186093-30-1
• 化学式: C₁₄H₂₈O₂S
• 分子量: 260.441
• InChiKey: DSQBWINXXHAPMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  17
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  12-thioethyldodecanoic acid 在 4-二甲氨基吡啶 、 草酰氯 作用下， 以 苯 为溶剂， 反应 6.0h， 生成 5'-O-(12-thioethyldodecanoyl)-2',3'-didehydro-2',3'-dideoxythymidine
  参考文献：
  名称：

  Synthesis and biological evaluation of fatty acyl ester derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine

  摘要：

  A number of 5'-O-fatty acyl derivatives of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T) were synthesized and evaluated for anti-HIV activities against cell-free and cell-associated virus, cellular cytotoxicity, and cellular uptake studies. The conjugates were found to be more potent than d4T. Among these conjugates, 5'-O-12-azidododecanoyl derivative of d4T (2), displaying EC50 = 3.1-22.4 mu M, showed 4- to 9-fold higher activities than d4T against cell-free and cell-associated virus. Cellular uptake studies were conducted on CCRF-CEM cell line using 5(6)-carboxyfluorescein derivatives of d4T attached through beta-alanine (9) or 12-aminododecanoic acid (10) as linkers. The fluorescein-substituted analog of d4T with long chain length (10) showed 12- to 15-fold higher cellular uptake profile than the corresponding analog with short chain length (9). These studies reveal that conjugation of fatty acids to d4T enhances the cellular uptake and anti-HIV activity of stavudine. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.070

文献信息

• Synthesis,<i>In Vitro</i>Anti-HIV Activity, and Biological Stability of 5′-<i>O</i>-Myristoyl Analogue Derivatives of 3′-Fluoro-2′,3′-Dideoxythymidine (FLT) as Potential Bifunctional Prodrugs of FLT
  作者：Keykavous Parang、Edward E. Knaus、Leonard I. Wiebe

  DOI：10.1080/07328319808004216

  日期：1998.6

  A group of 5'-O-myristoyl analogue derivatives of FLT (2) were evaluated as potential anti-HIV agents that were designed to serve as prodrugs to FLT. 3'-Fluoro-2',3'-dideoxy-5'-O-(12-methoxydodecanoyl)thymidine (4) (EC50 = 3.8 nM) and 3'-fluoro-2',3'-dideoxy-5'-O-(12-azidododecanoyl)thymidine (8) (EC50 = 2.8 nM) were the most effective anti-HIV-1 agents. There was a linear correlation between Log P

  一组FLT的5'-O-肉豆蔻酰基类似物衍生物（2）被评估为潜在的抗HIV药物，被设计用作FLT的前药。3'-氟-2'，3'-二脱氧-5'-O-（12-甲氧基十二烷酰基）胸苷（4）（EC50 = 3.8 nM）和3'-氟-2'，3'-二脱氧-5'- O-（12-叠氮基十二烷酰基）胸苷（8）（EC50 = 2.8 nM）是最有效的抗HIV-1药物。5'-O-FLT酯的Log P和HPLC Log保留时间之间存在线性关系。猪肝酯酶，大鼠血浆和大鼠脑匀浆中酯类（3-8）中的体外酶促水解半衰期（t1 / 2）较长，对于3'-氟-2'，3'-二脱氧-5'-O-（肉豆蔻酰基）胸苷（7），t1 / 2值分别为20.3、4.6和17.5分钟。
• Fatty acyl amide derivatives of doxorubicin: Synthesis and in vitro anticancer activities
  作者：Bhupender S. Chhikara、Nicole St. Jean、Deendayal Mandal、Anil Kumar、Keykavous Parang

  DOI：10.1016/j.ejmech.2011.02.056

  日期：2011.6

  Doxorubicin is extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety

  阿霉素被广泛用于抗癌治疗。阿霉素是高度亲水的，半衰期短，其使用与高剂量时的严重副作用有关。合成了阿霉素的脂肪酰基酰胺衍生物，以期改善该药物的亲脂性和抗癌活性。亲脂性随脂肪酰基部分链长的增加而增强。通过酰胺键将4'-氨基与脂肪酸缀合会降低白血病，乳腺癌，卵巢癌和结肠癌细胞系的抗癌活性，这表明阿霉素的抗癌活性需要游离氨基的存在。
• Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents
  作者：Bhupender S. Chhikara、Deendayal Mandal、Keykavous Parang

  DOI：10.1016/j.ejmech.2010.07.024

  日期：2010.10

  plasma half-life, and its use is associated with severe side effects. Fatty acyl derivatives of cytarabine were synthesized with the expectation to improve cellular uptake and generate derivatives with a longer duration of action. Multi-step protection and deprotection reactions of hydroxyl and amino groups and conjugation with a fatty acid (i.e., myristic acid and 12-thioethyldodecanoic acid) afforded

  阿糖胞苷是一种化学治疗剂，主要用于治疗急性髓细胞性白血病和淋巴母细胞性白血病。阿糖胞苷是一种极性核苷，血浆半衰期短，其使用会带来严重的副作用。合成了阿糖胞苷的脂肪酰基衍生物，以期改善细胞摄取并产生具有更长作用时间的衍生物。羟基和氨基的多步保护和脱保护反应以及与脂肪酸（即肉豆蔻酸和12-硫代乙基十二烷酸）的缀合产生5'- O-取代，2'- O阿糖胞苷的-取代的和2'，5'-二取代的脂肪酰基衍生物。孵育96小时后，发现阿糖胞苷的2'，5'-二肉豆蔻酰基衍生物在1μM的浓度下可抑制CCRF-CEM细胞的生长约76％。
• 5′-O-Ester Prodrugs of Potent and Selective Anti-HIV Agent—2′,3′-Dideoxy-3′-fluoro-2-thiothymidine (S²FLT): Synthesis and Anti-HIV Activity
  作者：A. Miazga、N. E. Poopeiko#、A. Piasek、M. A. Siweckar、T. Kulikowski

  DOI：10.1081/ncn-120022639

  日期：2003.10

  Abstract Novel synthesis of 2′,3′-dideoxy-3′-fluoro-2-thiothymidine (SFLT) based on transformation of appropriately protected 1-β-D-threo-ribofuranosylthymine is presented. The synthesis and evaluation of SFLT 5′-O-ester prodrugs enzymatic hydrolysis, as well as their anti-HIV activity, is also described.

  摘要提出了基于适当保护的1-β-D-苏-核呋喃呋喃基胸腺嘧啶的转化，合成2'，3'-二脱氧-3'-氟-2-硫代胸腺嘧啶（SFLT）的新方法。还描述了SFLT 5'-O-酯前药酶促水解的合成和评估，以及它们的抗HIV活性。
• Synthesis and Biological Evaluation of Fatty Acyl Ester Derivatives of (−)-2′,3′-Dideoxy-3′-thiacytidine
  作者：Hitesh K. Agarwal、Bhupender S. Chhikara、Michael J. Hanley、Guofeng Ye、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1021/jm300492q

  日期：2012.5.24

  A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC50 = 0.2-2.3 mu M) were more potent than the corresponding monosubstituted N-4-fatty acyl (EC50 = 0.4-29.4 mu M) and 5'-O-N-4-disubstituted (EC50 = 72.6 to >154.0 mu M) derivatives of the nucleoside. 5'-O-Myristoyl (16) and 5'-O-12-azidododecanoyl derivatives (17) were found to be the most potent compounds (EC50 = 0.2-0.9 mu M) exhibiting at least 16-36-fold higher anti-HIV activity against cell-free virus than 1 (EC50 = 11.4-32.7 mu M). The EC90 values for 16 against B-subtype and C-subtype clinical isolates were several folds lower than those of 1. The cellular uptake studies confirmed that compound 16 accumulated intracellularly after 1 h of incubation with CCRF-CEM cells and underwent intracellular hydrolysis. 5'-O-Fatty acyl derivatives of 1 showed significantly higher anti-HIV activity than the corresponding physical mixtures against the B-subtype virus.