chloromethyl tetradecanoate | 61413-68-1

• 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: chloromethyl tetradecanoate
• 英文别名: chloromethyl myristate
• CAS: 61413-68-1
• 化学式: C₁₅H₂₉ClO₂
• 分子量: 276.847
• InChiKey: OVADWGBRRBTXIB-UHFFFAOYSA-N

物化性质

• 沸点：
  329.7±15.0 °C(Predicted)
• 密度：
  0.951±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  18
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  chloromethyl tetradecanoate 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.67h， 生成 (5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-2,4-dioxothiazolidin-3-yl)methyl myristoate
  参考文献：
  名称：

  Prodrugs of Pioglitazone for Extended-Release (XR) Injectable Formulations

  摘要：

  N-Acyloxymethyl derivatives of pioglitazone (PIO) have been prepared and characterized as model candidates for extended-release injectable formulations. All PIO derivatives prepared are crystalline solids as determined by powder X-ray diffraction, and the solubility in aqueous media is below 1 mu M at 37 degrees C. The melting points steadily increase from 55 degrees C, for the hexanoyloxymethyl derivative, to 85 degrees C, for the palmitoyloxymethyl derivative; inversely, the solubilities in ethyl oleate decrease as a function of increasing acyl chain length. The butyroyloxymethyl ester has a higher melting point and a lower solubility in ethyl oleate than expected from the trend. The C-13 solid-state NMR spectra of the PIO homologues between the hexanoyloxymethyl derivative and stearoyloxymethyl derivative suggest a common structural motif with the acyl chains exchanging between two distinct conformations, and the rate of exchange is slower for longer chain derivatives. The butyroyloxymethyl derivative is efficiently converted to PIO in in vitro rat plasma with a half-life of <2 min at 37 degrees C, while the rate of enzymatic cleavage in rat plasma decreases as the ester chain length increases for the longer acyloxymethyl derivatives. The concentration of PIO in plasma increases rapidly, or "spikes," in the hours following intramuscular (IM) injection of either the HCl salt or the butyroyloxymethyl derivative. In contrast, the more lipophilic palmitoyloxymethyl derivative provides slow growth in the PIO concentration over the first day to reach levels that remain steady for 2 weeks. On the basis of its in vivo pharmacokinetic profile, as well as material and solubility properties, the PIO palmitoyloxymethyl derivative has potential as a once-monthly injectable medication to treat diabetes.

  DOI：

  10.1021/mp500359a
• 作为产物：
  描述：

  氯甲基氯磺酸酯 、 肉豆蔻酸 在 碳酸氢钠 、 四正丁基硫酸铵 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.0h， 以63.93%的产率得到chloromethyl tetradecanoate
  参考文献：
  名称：

  Opioid receptor antagonist prodrugs

  摘要：

  本文提供了阿片受体拮抗剂的前药，如纳美非林和纳曲酮，包括所述化合物的药物组合物，以及使用所述化合物治疗行为障碍的方法。

  公开号：

  US10533015B1

文献信息

• Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy
  作者：Boris Gaillard、Cendrine Seguin、Jean‐Serge Remy、Françoise Pons、Luc Lebeau

  DOI：10.1002/chem.201903976

  日期：2019.12.5

  Sixteen cationic prodrugs of the antitumor alkylphospholipid (APL) erufosine were rationally synthesized to provide original gene delivery reagents with improved cytotoxicity profile. The DNA complexation properties of these cationic lipids were determined and associated transfection rates were measured. Furthermore, the self-assembly properties of the pro-erufosine compounds were investigated and

  合理地合成了十六种抗肿瘤烷基磷脂（APL）肌苷的阳离子前药，以提供具有改善的细胞毒性特征的原始基因递送试剂。确定了这些阳离子脂质的DNA络合特性，并测量了相关的转染率。此外，研究了芥子油苷化合物的自组装性能，并确定了其临界聚集浓度。在模拟细胞外环境和晚期内体环境的pH条件下，测量了它们的水解稳定性。研究了这些化合物的溶血活性和细胞毒性。在各种细胞系中获得的结果表明，芥子碱的前药显示出与母体抗肿瘤药相似的抗肿瘤活性，但与溶血毒性无关，这是APL的剂量限制性副作用，是其在APL中使用的主要障碍抗癌治疗方案。此外，通过使用由芥酸前药和编码促凋亡蛋白（TRAIL）的质粒DNA制备的脂质复合物，提供了对肿瘤细胞的选择性细胞毒性而非肿瘤细胞具有抗性的证据。这项研究表明，包括良好耐受的芥酸阳离子前药和癌症基因治疗的组合方法在肿瘤治疗中具有重大前景。此外，通过使用由芥酸前药和编码促凋亡蛋白（TRAIL）的
• [EN] PRODRUGS OF CGRP ANTAGONISTS<br/>[FR] PROMÉDICAMENTS D'ANTAGONISTES DU CGRP
  申请人：BIOHAVEN PHARM HOLDING CO LTD

  公开号：WO2020077038A1

  公开（公告）日：2020-04-16

  Disclosed are prodrugs of CGRP antagonists, methods of treating CGRP related disorders, e.g., migraine, by administering to a patient in need thereof the prodrugs, pharmaceutical compositions comprising prodrugs and kits including the pharmaceutical compositions and instructions for use.

  披露了CGRP拮抗剂的前药，治疗CGRP相关疾病的方法，例如偏头痛，通过向需要的患者给予前药，包含前药的药物组合物以及包括药物组合物和使用说明的工具包。
• Esters of cephalosporin derivitives
  申请人：American Cyanamid Company

  公开号：US04914091A1

  公开（公告）日：1990-04-03

  Adamantane 1 carbonyloxymethyl 7.beta.-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1,2,3-th iadiazol-5 yl)-thiomethyl]ceph-3-em-4 carboxylate is disclosed. It and other esters are used as orally administered anti bacterials".

  Adamantane 1 carbonyloxymethyl 7.beta.-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1,2,3-thiadiazol-5-yl)-thiomethyl]ceph-3-em-4 carboxylate 被公开。它和其他酯类化合物被用作口服抗菌药。
• Fatty Acid-Derived Pro-Toxicants of the Rat Selective Toxicant Norbormide
  作者：Hans Choi、Daniel Conole、Darcy J. Atkinson、Olivia Laita、Morgan Jay-Smith、Mario Angelo Pagano、Giovanni Ribaudo、Maurizio Cavalli、Sergio Bova、Brian Hopkins、Margaret A. Brimble、David Rennison

  DOI：10.1002/cbdv.201500241

  日期：2016.6

  evaluation (vasocontractile response in rat vasculature, stability in selected rat media) and palatability/efficacy in Sprague-Dawley, wild Norway, and wild ship rats is described. Most notably, pro-toxicant 3d was revealed to be free of all pre-cleavage vasoconstrictory activity in rat caudal artery and was subsequently demonstrated to release NRB in the presence of rat blood, liver, and pancreatic enzymes

  已知存在但很少使用的杀虫剂降冰片[5-（α-羟基-α-2-吡啶基苄基）-7-（α-2-吡啶基苄基）-5-降冰片烯-2,3-二甲酰亚胺]（NRB）对大鼠有独特的毒性，但对其他啮齿动物和哺乳动物则无害。但是，作为一种急性血管活性物质，NRB具有起效快的作用，因此它对大鼠相对不受欢迎，经常导致摄入不足致死率并伴有诱饵害羞。为了“掩盖”这种急性反应并改善适口性和功效，准备了一系列NRB衍生的前毒物（3a-i，4a-i和5a-i）。描述了它们的合成，体外生物学评估（大鼠脉管系统中的血管收缩反应，所选大鼠培养基中的稳定性）以及Sprague-Dawley，挪威野生动物和野船大鼠的适口性/功效。最为显着地，前毒素3d被发现在大鼠尾动脉中没有所有卵裂前的血管收缩活性，随后被证明在存在大鼠血液，肝脏和胰腺酶的情况下释放NRB。此外，它在两项选择诱饵适口性和功效试验中始终显示出高水平的被大鼠接受，并伴有高死亡
• Ester of cephalosporin derivatives
  申请人：AMERICAN CYANAMID COMPANY

  公开号：EP0157000A2

  公开（公告）日：1985-10-09

  Esters of cephalosporin derivatives which can be orally administered and used as prodrugs are disclosed.

  本研究公开了可口服并用作原药的头孢菌素衍生物酯类。