ethyl 16-aminohexadecanoate

• 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: ethyl 16-aminohexadecanoate
• 化学式: C₁₈H₃₇NO₂
• 分子量: 299.497
• InChiKey: XFAUXIZHAXMLBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  21
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 16-aminohexadecanoate 在 乙醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 16-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid
  参考文献：
  名称：

  [EN] OMEGA-3 ANALOGUES
  [FR] ANALOGUES D'OMÉGA-3

  摘要：

  本发明涉及新的脂肪酸类似物及其在癌症治疗中的使用，包括抗转移治疗。

  公开号：

  WO2014078895A1
• 作为产物：
  描述：

  16-羟基棕榈酸 在 偶氮二甲酸二异丙酯 、 乙酰氯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 41.0h， 生成 ethyl 16-aminohexadecanoate
  参考文献：
  名称：

  [EN] OMEGA-3 ANALOGUES
  [FR] ANALOGUES D'OMÉGA-3

  摘要：

  本发明涉及新的脂肪酸类似物及其在癌症治疗中的使用，包括抗转移治疗。

  公开号：

  WO2014078895A1

文献信息

• Aryl-urea fatty acids that activate the p38 MAP kinase and down-regulate multiple cyclins decrease the viability of MDA-MB-231 breast cancer cells
  作者：Yassir Al-Zubaidi、Curtis Pazderka、Nooshin Koolaji、Md Khalilur Rahman、Hassan Choucair、Bala Umashankar、Kirsi Bourget、Yongjuan Chen、Tristan Rawling、Michael Murray

  DOI：10.1016/j.ejps.2018.12.015

  日期：2019.3

  xenograft models in vivo. At present there is a deficiency of information on the structural requirements for the activity of CTU. Our initial study suggested that electron withdrawing groups were required on the aryl ring, and in this study we further evaluated the influence of the electronic properties of aromatic substitution on the capacity of CTU analogues to decrease MDA-MB-231 breast cancer cell viability

  我们最近开发了一种新型的芳基脲脂肪酸（CTU； 16（[4-氯-3-（三氟甲基）苯基]氨基甲酰基}氨基）十六烷酸）可削弱MDA-MB-231乳腺癌细胞在体外的生存能力和体内小鼠异种移植模型。目前，关于货运单元活动的结构要求的信息不足。我们的初步研究表明芳基环上需要吸电子基团，并且在这项研究中，我们进一步评估了芳族取代基的电子性质对CTU类似物降低MDA-MB-231乳腺癌细胞生存能力的影响。在芳基环的间位和对位含有强吸电子基团的类似物表现出比CTU更高的活性。有效的类似物下调了细胞周期蛋白D1，E1和B1，以及细胞周期蛋白依赖性激酶（CDK）4和6，它们形成复合物以协调细胞周期进程。活性CTU类似物还刺激细胞中p38 MAP激酶信号通路的磷酸化和激活，并降低增殖（5-溴2'-脱氧尿苷（brdU）掺入）和激活的细胞凋亡（执行子caspase-3 / 7活性）。这些药物提供了一种针对多个阶段
• Synthesis, radiolabeling and evaluation of a new positively charged 99mTc-labeled fatty acid derivative for myocardial imaging
  作者：Anupam Mathur、Madhava B. Mallia、Haladhar D. Sarma、Sharmila Banerjee、Meera Venkatesh

  DOI：10.1002/jlcr.1836

  日期：2011.3

  123I-labeled fatty acids and 18F-FDG are used as metabolic markers for detecting myocardial abnormalities. However, a 99mTc-based molecule may find wider application. In the present work, a new 99mTc-labeled, uni-positively charged, 16-carbon fatty acid has been prepared and evaluated in normal Swiss mice. The results are then compared with the neutral analogue reported earlier. A 16-cysteinyl hexadecanoic acid conjugate was synthesized in a six-step synthetic procedure starting with 16-bromohexadecanoic acid. The ligand upon incubation with [99mTcN(PNP6)]2+ core formed the required positively charged complex in ∼85% yield. The complex, which was obtained as a mixture of syn-anti isomers, was purified by HPLC and the major fraction was used for in vivo studies in Swiss mice. The biodistribution studies in Swiss mice showed initial uptake similar to 125I-IPPA followed by rapid clearance from the myocardium till 10 min p.i. Thereafter, the rate of clearance was significantly decreased, an observation reported earlier for positively charged fatty acid complexes. In terms of absolute uptake, the positively charged complex performed better than the neutral analogue reported earlier. The positively charged fatty acid complexes, prepared using [99mTcN(PNP)]2+ core, seems to be better candidates for the development of myocardial metabolic tracers than their neutral counterparts. Copyright © 2010 John Wiley & Sons, Ltd.

  123I 标记的脂肪酸和 18F-FDG 被用作检测心肌异常的代谢标记物。然而，基于 99mTc 的分子可能会有更广泛的应用。本研究制备了一种新的 99mTc 标记、带单正电荷的 16 碳脂肪酸，并在正常瑞士小鼠体内进行了评估。然后将结果与之前报告的中性类似物进行了比较。 以 16-溴十六烷酸为起点，通过六步合成程序合成了 16-半胱氨酰十六烷酸共轭物。该配体与[99mTcN(PNP6)]2+ 核孵育后形成了所需的带正电荷的复合物，收率高达 85%。通过高效液相色谱法（HPLC）纯化了以同分异构体混合物形式获得的复合物，并将主要部分用于瑞士小鼠体内研究。在瑞士小鼠体内进行的生物分布研究表明，该复合物的初始摄取量与 125I-IPPA 相似，随后迅速从心肌中清除，直至 10 分钟后才被清除。就绝对摄取量而言，带正电荷的复合物比之前报道的中性类似物表现更好。使用[99mTcN(PNP)]2+核心制备的正电荷脂肪酸复合物似乎比中性复合物更适合开发心肌代谢示踪剂。Copyright © 2010 John Wiley & Sons, Ltd. All Rights Reserved.
• OMEGA-3 ANALOGUES
  申请人：The University of Sydney

  公开号：US20150322001A1

  公开（公告）日：2015-11-12

  The present invention relates to new fatty acid analogues and to their use in cancer therapy, including antimetastatic therapy.

  本发明涉及新的脂肪酸类似物及其在癌症治疗中的应用，包括抗转移治疗。
• NOVEL PYRIDINECARBOXAMIDE DERIVATIVES
  申请人：Nisshin Flour Milling Co., Ltd.

  公开号：EP0885886A1

  公开（公告）日：1998-12-23

  Pyridinecarboxamide derivatives of the formula (wherein n represents an integer of 14 - 18, and R represents a hydrogen atom or a straight or branched C1-C4 alkyl group) or physiologically acceptable salts thereof. The compounds have excellent inhibiting activity of cerebral edema, especially ischemic cerebral edema, and inhibiting activity of delayed death of neuronal cells (an inhibiting activity of Ca-influx in neuronal cells). Cerebral edema is a pathologic condition accompanying cerebrovascular disorders, especially the acute stage of cerebrovascular disorders and then the compounds are useful as an agent for inhibiting cerebral edema or a therapeutic agent for cerebrovascular disorders. Moreover, the compounds have no hypotensive action which is considered to be side-effect in treating the acute stage cerebrovascular disorders and hardly show a behavior suppressing action so that they are an excellent therapeutic agent for, in particular, the acute stage cerebrovascular disorders. Moreover, the compounds show a cerebral protective activity (an anti-anoxic activity), an increasing activity of cerebral blood flow, and an inhibiting activity of lipid peroxidation and these activities may lead to the increased utility as a therapeutic agent for cerebrovascular disorders.

  式中的吡啶甲酰胺衍生物 (其中 n 代表 14 - 18 的整数，R 代表氢原子或直链或支链 C1-C4 烷基）或其生理上可接受的盐。 这些化合物对脑水肿，尤其是缺血性脑水肿有很好的抑制作用，对神经元细胞的延迟死亡也有很好的抑制作用（抑制神经元细胞中 Ca 的内流）。脑水肿是脑血管疾病，尤其是脑血管疾病急性期的一种病理状态，因此，这些化合物可作为抑制脑水肿的药物或脑血管疾病的治疗药物。此外，这些化合物在治疗急性期脑血管疾病时没有被认为是副作用的降压作用，也几乎没有行为抑制作用，因此是一种特别适用于急性期脑血管疾病的优良治疗剂。此外，这些化合物还显示出脑保护活性（抗缺氧活性）、增加脑血流量活性和抑制脂质过氧化活性，这些活性可能会增加其作为脑血管疾病治疗剂的效用。
• A Novel Arylurea Fatty Acid That Targets the Mitochondrion and Depletes Cardiolipin To Promote Killing of Breast Cancer Cells
  作者：Tristan Rawling、Hassan Choucair、Nooshin Koolaji、Kirsi Bourget、Sarah E. Allison、Yong-Juan Chen、Colin R. Dunstan、Michael Murray

  DOI：10.1021/acs.jmedchem.7b00701

  日期：2017.10.26

  Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized arylurea fatty acids and found that the analogue 16-([4-chloro-3-(trifluoromethyl)-phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death.