12-azidododecanoyl chloride | 200720-60-1

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 12-azidododecanoyl chloride
• 英文别名: 12-Azidododecanoyl chloride
• CAS: 200720-60-1
• 化学式: C₁₂H₂₂ClN₃O
• 分子量: 259.779
• InChiKey: KDPRVVQXWANKKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  17
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  31.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  拉米夫定 、 12-azidododecanoyl chloride 在 4-二甲氨基吡啶 作用下， 以 苯 为溶剂， 反应 4.0h， 以55%的产率得到(-)-N(4)-5'-di(12-azidododecanoyl)-2',3'-dideoxy-3'-thiacytidine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Fatty Acyl Ester Derivatives of (−)-2′,3′-Dideoxy-3′-thiacytidine

  摘要：

  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.

  DOI：

  10.1021/jm300492q
• 作为产物：
  描述：

  12-溴十二烷酸 在 氯化亚砜 、 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 12-azidododecanoyl chloride
  参考文献：
  名称：

  The total synthesis of a technetium chelate - tamoxifen complex

  摘要：

  通过对抗雌激素的他莫昔芬进行衍生化合成了一种用于成像乳腺癌的潜在成像剂。需要进行多步合成，将锝螯合物与他莫昔芬结合，使复合物的生物分布模拟母化合物的分布。关键词：他莫昔芬、放射成像、锝、合成。

  DOI：

  10.1139/v98-220

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。
• [EN] FATTY ACYL AND FATTY ETHER CONJUGATES OF REMDESIVIR AND ITS ACTIVE METABOLITES AS ANTIVIRALS<br/>[FR] CONJUGUÉS D'ACYLE GRAS ET D'ÉTHER GRAS DE REMDÉSIVIR ET SES MÉTABOLITES ACTIFS EN TANT QU'ANTIVIRAUX
  申请人：AJK PHARMACEUTICAL LLC

  公开号：WO2021222807A1

  公开（公告）日：2021-11-04

  Antiviral compounds, pharmaceutical compositions containing the same, and methods of treating viral infections or medical disorders resulting from viral infections are disclosed.

  本发明公开了抗病毒化合物、含有该化合物的药物组合物以及治疗病毒感染或由病毒感染引起的医疗疾病的方法。
• Synthesis and biological evaluation of fatty acyl ester derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine
  作者：Hitesh K. Agarwal、Kelly Loethan、Deendayal Mandal、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1016/j.bmcl.2011.02.070

  日期：2011.4

  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.
• Synthesis and antiviral activity of fatty acyl conjugates of remdesivir against severe acute respiratory syndrome coronavirus 2 and Ebola virus
  作者：Naglaa Salem El-Sayed、Alexander S. Jureka、Megan R. Edwards、Sandeep Lohan、Caroline G. Williams、Patrick T. Keiser、Robert A. Davey、Jennifer Totonchy、Rakesh K. Tiwari、Christopher F. Basler、Keykavous Parang

  DOI：10.1016/j.ejmech.2021.113862

  日期：2021.12
• OPTICAL SENSOR SYSTEM FOR pH DETERMINATION INDEPENDENTLY OF THE ION STRENGTH USING FLUORESCEIN BOUND TO A POLYMER VIA A URETHANE AND/OR UREA GROUP
  申请人：Novartis AG

  公开号：EP0906566A1

  公开（公告）日：1999-04-07