(E)-2-chloro-N-(3,7-dimethylocta-2,6-dien1-yl)acetamide | 627527-81-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E)-2-chloro-N-(3,7-dimethylocta-2,6-dien1-yl)acetamide
• 英文别名: (E)-2-chloro-N-(3,7-dimethylocta-2,6-dienyl)acetamide；2-chloro-N-[(2E)-3,7-dimethylocta-2,6-dienyl]acetamide
• CAS: 627527-81-5
• 化学式: C₁₂H₂₀ClNO
• 分子量: 229.75
• InChiKey: OUQGMTYENXRYQE-YRNVUSSQSA-N

物化性质

• 沸点：
  379.0±42.0 °C(Predicted)
• 密度：
  0.995±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (E)-2-chloro-N-(3,7-dimethylocta-2,6-dien1-yl)acetamide 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 32.5h， 生成 (E)-N-(2-((1r,3r,5r,7r)-adamantan-2-yloxy)ethyl)-3,7-dimethylocta-2,6-dien-1-amine
  参考文献：
  名称：

  Multitarget Drug Discovery for Tuberculosis and Other Infectious Diseases

  摘要：

  We report the discovery of a series of new drug leads that have potent activity against Mycobacterium tuberculosis as well as against other bacteria, fungi, and a malaria parasite. The compounds are analogues of the new tuberculosis (TB) drug SQ109 (1), which has been reported to act by inhibiting a transporter called MmpL3, involved in cell wall biosynthesis. We show that 1 and the new compounds also target enzymes involved in menaquinone biosynthesis and electron transport, inhibiting respiration and ATP biosynthesis, and are uncouplers, collapsing the pH gradient and membrane potential used to power transporters. The result of such multitarget inhibition is potent inhibition of TB cell growth, as well as very low rates of spontaneous drug resistance. Several targets are absent in humans but are present in other bacteria, as well as in malaria parasites, whose growth is also inhibited.

  DOI：

  10.1021/jm500131s
• 作为产物：
  描述：

  香叶胺 、 氯乙酰氯 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以81%的产率得到(E)-2-chloro-N-(3,7-dimethylocta-2,6-dien1-yl)acetamide
  参考文献：
  名称：

  Novel polycyclic ‘cage’-1,2-diamines as potential anti-tuberculosis agents

  摘要：

  A series of polycyclic 'cage' derivatives of N-geranyl-1,2 diamines were synthesized and screened for their anti-mycobacterial activity against H(37)Rv, multidrug resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis. By substituting the adamantyl skeleton of SQ109 with trishomocubanyl (9), oxa-pentacycloundecyl (14, 16), pentacycloundecyl, PCU, (10, 15) and azapentacycloundecyl (22, 23), the effect of other polycyclic "cage" skeletons could be investigated. Compound 9 (trishomocubanyl moiety) proved to be the most active (MICs: 0.5-2 mu g/mL) while PCU hydroxyl derivatives (15 and 23), oxa-pentacycloundecyl and azapentacycloundecyl derivatives displayed similar activity to SQ109 (MICs: 0.5-4 mu g/mL) against all three strains of TB used in this study. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.041

文献信息

• Structure, <i>In Vivo</i> Detection, and Antibacterial Activity of Metabolites of SQ109, an Anti-Infective Drug Candidate
  作者：Satish R. Malwal、Matthew D. Zimmerman、Nadine Alvarez、Jansy P. Sarathy、Véronique Dartois、Carol A. Nacy、Eric Oldfield

  DOI：10.1021/acsinfecdis.1c00259

  日期：2021.8.13

  it has been proposed that some of its metabolites might be responsible for its activity against TB. Here, we synthesized six potential P450 metabolites of SQ109 and used these as well as 10 other likely metabolites as standards in a mass spectrometry study of M. tuberculosis-infected rabbits treated with SQ109, in addition to testing all 16 putative metabolites for antibacterial activity. We found that

  SQ109 是治疗结核病 (TB) 的候选药物。它被认为主要针对结核分枝杆菌中的蛋白质 MmpL3 ，但它也抑制其他一些细菌的生长。SQ109 由肝脏代谢，有人提出它的一些代谢物可能是其抗结核病活性的原因。在这里，我们合成了 SQ109 的 6 种潜在 P450 代谢物，并将这些以及 10 种其他可能的代谢物用作用 SQ109 治疗的结核分枝杆菌感染兔的质谱研究的标准，此外还测试了所有 16 种推定代谢物的抗菌活性。我们发现肺组织中只有两种主要代谢物：SQ109 的羟基金刚烷基类似物和N'-金刚烷基乙二胺。这些或测试的其他潜在代谢物均未抑制结核分枝杆菌或耻垢分枝杆菌、枯草芽孢杆菌或大肠杆菌的生长，因此 SQ109 代谢物不太可能有助于其抗菌活性。因此，在兔 TB 模型中，非代谢的 SQ109 在组织中逐渐积累到治疗水平会导致良好的疗效。我们的结果还提供了关于 SQ109 如何与其目标 MmpL3
• Methods of use and compositions for the diagnosis and treatment of infectious disease
  申请人：——

  公开号：US20030236225A1

  公开（公告）日：2003-12-25

  Methods and compositions for treating disease caused by microorganisms, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.

  方法和组合物用于治疗由微生物引起的疾病，特别是结核病。具体而言，提供了用于治疗传染病的取代乙烯二胺的方法和组合物。在一种实施方式中，这些方法和组合物用于治疗分枝杆菌感染，包括但不限于结核病。
• ANTI-TUBERCULAR DRUGS: COMPOSITIONS AND METHODS
  申请人：PROTOPOPOVA Marina Nikolaevna

  公开号：US20090192173A1

  公开（公告）日：2009-07-30

  Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis. In certain embodiments, the present invention comprises compositions comprising novel substituted ethylene diamine compounds further comprising antitubercular agents such as rifampicin, isoniazid, pyrazinamide and ethambutol.

  本发明提供了用于治疗由传染性病原体引起的疾病，特别是结核病的方法和组合物。具体而言，提供了用于治疗传染病的取代乙二胺的方法和组合物。在一个实施例中，这些方法和组合物用于治疗分枝杆菌感染，包括但不限于结核病。在某些实施例中，本发明包括包含新型取代乙二胺化合物的组合物，进一步包括抗结核药物如利福平、异烟肼、吡嗪酰胺和乙胺丁醇。
• Anti tubercular drug: compositions and methods
  申请人：——

  公开号：US20040033986A1

  公开（公告）日：2004-02-19

  Methods and compositions for treating disease caused by infectious agents, particularly tuberculosis. In particular, methods and compositions comprising substituted ethylene diamines for the treatment of infectious diseases are provided. In one embodiment, these methods and compositions are used for the treatment of mycobacterial infections, including, but not limited to, tuberculosis.

  治疗由传染性病原体，特别是结核病引起的疾病的方法和组合物。特别是提供了包含取代乙二胺的治疗传染性疾病的方法和组合物。在一个实施方案中，这些方法和组合物用于治疗分枝杆菌感染，包括但不限于结核病。
• Synthesis of novel [1,2]-diamines with antituberculosis activity
  作者：Qingyi Meng、Huibing Luo、Yilang Chen、Tiancai Wang、Qizheng Yao

  DOI：10.1016/j.bmcl.2009.07.126

  日期：2009.9

  Guided by the metabolism information of SQ109, derivatives with substituted geranylamine moiety or substituted admantane ring of SQ109 were synthesized and evaluated as antituberculosis agents. Among all tested compounds, compound 11c showed the most potent antituberculosis activity with MIC value of 0.3 mu M against Mycobacterium tuberculosis H37Rv. (C) 2009 Elsevier Ltd. All rights reserved.