5-chloro-2-hexyl-1-methyl-1H-indole | 1254320-67-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-chloro-2-hexyl-1-methyl-1H-indole
• 英文别名: 5-chloro-2-hexyl-1-methylindole
• CAS: 1254320-67-6
• 化学式: C₁₅H₂₀ClN
• 分子量: 249.784
• InChiKey: QCEBEPYGXFVTQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  二甘醇酐 、 5-chloro-2-hexyl-1-methyl-1H-indole 在 二甲基氯化铝 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 2-(2-(5-chloro-2-hexyl-1-methyl-1H-indol-3-yl)-2-oxoethoxy)acetic acid
  参考文献：
  名称：

  的结构-活性关系研究β氧化作用抗性基于吲哚-5-氧代6,8,11,14二十碳四烯酸（5-氧代ETE）受体拮抗剂

  摘要：

  5-Oxo-6,8,11,14-二十碳四烯酸（5-oxo-ETE）由5 S-羟基-6,8,11,14-二十碳四烯酸（5-HETE）通过5-脂氧合酶（ 5-LO）途径在与氧化应激相关的条件下。5-Oxo-ETE是重要的促炎介质，它通过选择性的G蛋白偶联受体OXE受体（OXE-R）刺激嗜酸性粒细胞的迁移。以前，我们设计并合成了5-oxo-ETE的结构模拟物，例如1使用吲哚支架。在目前的工作中，我们在该部分的C-3处添加了各种取代基，以阻断5-氧代戊酸酯侧链的潜在β-氧化，并研究了所得新型β-抗氧化拮抗剂的结构-活性关系。环丙基和环丁基取代基在该位置具有良好的耐受性，但作为高活性3 S-甲基化合物的效力较低。3-烷基取代基似乎可以影响含有关键的酮基和羧基的5-氧戊酸侧链的构象，从而影响与OXE-受体的相互作用。

  DOI：

  10.1016/j.bmcl.2017.08.034
• 作为产物：
  描述：

  5-氯-1H-吲哚-2-甲醛 在 palladium 10% on activated carbon 、 氢气 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 13.0h， 生成 5-chloro-2-hexyl-1-methyl-1H-indole
  参考文献：
  名称：

  Inhibition of 5-Oxo-6,8,11,14-eicosatetraenoic Acid-Induced Activation of Neutrophils and Eosinophils by Novel Indole OXE Receptor Antagonists

  摘要：

  5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a 5-lipoxygenase product that is a potent granulocyte chemoattractant, which induces the infiltration of eosinophils into human skin when injected intradermally. It could therefore be an important proinflammatory mediator in eosinophilic diseases such as asthma and allergic rhinitis, and the OXE receptor, which mediates its actions, is therefore an attractive drug target. Using a Structure-based approach in which substituents mimicking the essential polar (C-1-C-5) and hydrophobic (C-15-C-20) regions of 5-oxo-ETE were incorporated on an indole scaffold, we identified two potent selective OXE antagonists with IC50 values of about 30 nM Neither compound displayed agonist activity and both inhibited 5-oxo-ETE-induced chemotaxis and actin polymerization and were relatively resistant to metabolism by rat liver homogenates. The active enantiomers of these racemic antagonists were even more potent, with IC50 values of <10 nM. These selective OXE antagonists could potentially be useful therapeutic agents in allergic diseases such as asthma.

  DOI：

  10.1021/jm401292m
• 作为试剂：
  描述：

  5-chloro-2-hexylindole 、 氢氧化钾 、 碘甲烷 在 氯化铵 、 乙酸乙酯 、 5-chloro-2-hexyl-1-methyl-1H-indole 作用下， 以 二甲基亚砜 为溶剂， 反应 3.5h， 生成 5-chloro-2-hexyl-1-methyl-1H-indole
  参考文献：
  名称：

  5-OXO-ETE RECEPTOR ANTAGONIST COMPOUNDS

  摘要：

  本发明涉及一种新型药用化合物，其为5-oxo-ETE受体（如OXE受体）的拮抗剂。这些化合物可用作治疗和/或预防组织嗜酸性细胞增多症的疾病的治疗剂和/或预防剂，例如包括呼吸系统疾病在内的炎症性疾病。本发明还涉及制药组合物，使用这种化合物和组合物作为药物以及治疗方法。

  公开号：

  US20120122942A1

文献信息

• [EN] 5-OXO-ETE RECEPTOR ANTAGONIST COMPOUNDS<br/>[FR] COMPOSÉS ANTAGONISTES DES RÉCEPTEURS 5-OXO-ETE
  申请人：UNIV MCGILL

  公开号：WO2010127452A1

  公开（公告）日：2010-11-11

  The present invention relates to novel pharmaceutically-useful compounds which are antagonists of the 5-oxo-ETE receptors, such as the OXE receptor. These compounds have use as therapeutic and/or prophylactic agents for diseases characterized by tissue eosinophilia, such as inflammatory conditions including respiratory diseases. The invention also relates to pharmaceutical compositions, to the use of such compounds and compositions as medicaments, and to therapeutic methods.

  本发明涉及一种新型的药用化合物，它们是5-oxo-ETE受体的拮抗剂，如OXE受体。这些化合物可用作治疗和/或预防组织嗜麻细胞增多等疾病的药物，如包括呼吸道疾病在内的炎症性疾病。该发明还涉及制药组合物，以及将这些化合物和组合物用作药物、以及治疗方法。
• Stereoselective synthesis of two highly potent 5-oxo-ETE receptor antagonists
  作者：Chintam Nagendra Reddy、Qiuji Ye、Shishir Chourey、Sylvie Gravel、William S. Powell、Joshua Rokach

  DOI：10.1016/j.tetlet.2015.10.097

  日期：2015.12

  Enantioselective synthesis of highly potent 5-oxo-ETE receptor antagonists 5a and 6a with a high level of enantiomeric purity is described. The main feature of this work is the simple and efficient synthesis of the bi-functionalized 3-(S)-methyl-pentanedioic acid monomethyl ester (24) with the enantiomeric ratio of S/R:98.4/1.6. We investigated the asymmetric conjugate addition of MeMgBr to 5-Benzyloxy-pent-2-enoic

  描述了具有高水平对映体纯度的高效5-oxo-ETE受体拮抗剂5a和6a的对映选择性合成。这项工作的主要特点是简单有效地合成对映体比率为S / R：98.4 / 1.6的双官能化3-（S）-甲基戊二酸单甲酯（24）。我们研究了MeMgBr在CuBr /（S）-Tol-BINAP系统催化下的5-苯甲氧基-戊-2-烯酸甲酯（23）的不对称共轭加成反应，并优化了反应条件的区域选择性和高对映选择性。
• 5-oxo-ETE receptor antagonist compounds
  申请人：Powell William S.

  公开号：US08809382B2

  公开（公告）日：2014-08-19

  The present invention relates to novel pharmaceutically-useful compounds which are antagonists of the 5-oxo-ETE receptors, such as the OXE receptor. These compounds have use as therapeutic and/or prophylactic agents for diseases characterized by tissue eosinophilia, such as inflammatory conditions including respiratory diseases. The invention also relates to pharmaceutical compositions, to the use of such compounds and compositions as medicaments, and to therapeutic methods.

  本发明涉及一种新的药用化合物，它们是5-oxo-ETE受体的拮抗剂，例如OXE受体。这些化合物可用作治疗和/或预防组织嗜酸性粒细胞增多的疾病的药物，例如包括呼吸系统疾病在内的炎症性疾病。本发明还涉及制药组合物、使用这些化合物和组合物作为药物以及治疗方法。
• Two Potent OXE-R Antagonists: Assignment of Stereochemistry
  作者：Pranav Patel、Chintam Nagendra Reddy、Vivek Gore、Shishir Chourey、Qiuji Ye、Yannick P. Ouedraogo、Sylvie Gravel、William S. Powell、Joshua Rokach

  DOI：10.1021/ml500161v

  日期：2014.7.10

  5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is formed by the oxidation of 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic add (5-HETE), which is a major metabolite of enzymatic oxidation of arachidonic acid (AA). 5-Oxo-ETE is the most potent lipid chemoattractant for human eosinophils. Its actions are mediated by the selective OXE receptor, which is therefore an attractive target in eosinophilic diseases such as allergic rhinitis and asthma. Recently, we have reported two excellent OXE receptor antagonists that have IC50 values at low nanomolar concentrations. Each of these antagonists has a chiral center, and the isolation of the individual enantiomers by chiral high-performance liquid chromatography (HPLC) revealed that in each case one enantiomer is over 300 times more potent than the other. To unambiguously stereochemistry of these enantiomers and to provide access to larger amounts of the active compounds for biologicalassign the testing, we report here their total synthesis.
• US8809382B2
  申请人：——

  公开号：US8809382B2

  公开（公告）日：2014-08-19