iodomethyl tetradecanoate

• 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: iodomethyl tetradecanoate
• 英文别名: tetradecanoyloxymethyl iodide
• 化学式: C₁₅H₂₉IO₂
• 分子量: 368.299
• InChiKey: BJKCAYIOCCKSED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 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：

  iodomethyl tetradecanoate 、 5-[[4-[2-(5-乙基吡啶-2-基)乙氧基]苯基]甲基]-1,3-噻唑烷-2,4-二酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 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：

  chloromethyl tetradecanoate 在 碳酸氢钠 、 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 12.0h， 生成 iodomethyl 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
• 作为试剂：
  描述：

  达芦那韦 在 sodium hydride 、 iodomethyl tetradecanoate 作用下， 以 四氢呋喃 为溶剂， 反应 48.25h， 生成
  参考文献：
  名称：

  Synthesis and Characterization of Long-Acting Darunavir Prodrugs

  摘要：

  Antiretroviral therapy (ART) has improved the quality of life in patients infected with HIV-1. However, complete viral suppression within anatomical compartments remains unattainable. This is complicated by adverse side effects and poor adherence to lifelong therapy leading to the emergence of viral drug resistance. Thus, there is an immediate need for cellular and tissue-targeted long-acting (LA) ART formulations. Herein, we describe two LA prodrug formulations of darunavir (DRV), a potent antiretroviral protease inhibitor. Two classes of DRV prodrugs, M1DRV and M2DRV, were synthesized as lipophilic and hydrophobic prodrugs and stabilized into aqueous suspensions designated NM1DRV and NM2DRV. The formulations demonstrated enhanced intracellular prodrug levels with sustained drug retention and antiretroviral activities for 15 and 30 days compared to native DRV formulation in human monocyte-derived macrophages. Pharmacokinetics tests of NM1DRV and NM2DRV administered to mice demonstrated sustained drug levels in blood and tissues for 30 days. These data, taken together, support the idea that LA DRV with sustained antiretroviral responses through prodrug nanoformulations is achievable.

  DOI：

  10.1021/acs.molpharmaceut.9b00871

文献信息

• Opioid receptor antagonist prodrugs
  申请人：Nirsum Laboratories, Inc.

  公开号：US10533015B1

  公开（公告）日：2020-01-14

  Provided herein are prodrugs of opioid receptor antagonists such as nalmefene and naltrexone, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of behavioral disorders.

  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。
• 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。
• Prodrugs for the Treatment of Schizophrenia and Bipolar Disease
  申请人：Blumberg Laura Cook

  公开号：US20110166156A1

  公开（公告）日：2011-07-07

  Compounds of Formula I and Formula II and their use for the treatment of neurological and psychiatric disorders including schizophrenia and manic or mixed episodes associated with bipolar I disorder with or without psychotic features is disclosed.

  本文披露了公式I和公式II的化合物及其用于治疗神经系统和精神障碍，包括与双相I型障碍伴有或不伴有精神症状的精神分裂症和躁狂或混合发作的治疗。
• Quaternary Ammonium Salt Prodrugs
  申请人：Almarsson Orn

  公开号：US20110178068A1

  公开（公告）日：2011-07-21

  The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X − . In one embodiment, the present invention provides a prodrug compound of Formula I: where R 1 -R 5 are defined in the written description of the invention. The prodrug compounds of the invention can be used to treat any condition for which the tertiary amine-containing parent drug or tertiary imine-containing parent drug is useful as a treatment.

  本发明提供了一种持续释放三级胺含有的母药的方法，包括向患者施用本发明的前药化合物的有效量，其中在向患者施用时，母药从前药中的释放是持续释放的。适用于本发明方法的前药化合物是由醛基连接的前药基团衍生的，这些前药基团可以减少前药化合物在参考pH下的溶解度与母药相比。这些衍生物的物理、化学和溶解度特性可以通过选择阴离子X-来进一步调节。在一种实施方式中，本发明提供了式I的前药化合物：其中R1-R5在发明的书面描述中被定义。本发明的前药化合物可用于治疗任何需要使用三级胺含有的母药或三级亚胺含有的母药进行治疗的情况。
• 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。