2-(1-benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)ethanol | 479422-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(1-benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)ethanol
• 英文别名: 2-(1-Benzhydryl-5-chloro-2-methylindol-3-yl)ethanol
• CAS: 479422-74-7
• 化学式: C₂₄H₂₂ClNO
• 分子量: 375.898
• InChiKey: MNIWFAVBRRZHFN-UHFFFAOYSA-N

物化性质

• 沸点：
  574.9±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  25.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(1-benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)ethanol 在 四溴化碳 、 1,3-双(二苯基膦)丙烷 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 methyl 3-[4-[[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethyl]thio]phenyl]propanoate
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882
• 作为产物：
  描述：

  乙酰丙酸乙酯 在 lithium aluminium tetrahydride 、 sodium hydride 、 碳酸氢钠 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-(1-benzhydryl-5-chloro-2-methyl-1H-indol-3-yl)ethanol
  参考文献：
  名称：

  Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization

  摘要：

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.

  DOI：

  10.1021/jm0507882

文献信息

• Discovery of substituted indole derivatives as allosteric inhibitors of<scp>m⁶A‐RNA</scp>methyltransferase,<scp>METTL3</scp>‐14 complex
  作者：Je‐Heon Lee、Subin Kim、Mi Sun Jin、Yong‐Chul Kim

  DOI：10.1002/ddr.21910

  日期：——

  important roles in mRNA functions, and it has been implicated in the progression of multiple cancers, including acute myeloid leukemia (AML). In this study, we describe the discovery of the first allosteric inhibitor of the METTL3-14 complex based on structure–activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic

  m 6 RNA 甲基转移酶 (METTL3-14) 催化 mRNA 中腺苷的甲基化并在 mRNA 功能中发挥重要作用，它与多种癌症的进展有关，包括急性髓性白血病 (AML)。在这项研究中，我们描述了基于构效关系 (SAR) 的 METTL3-14 复合物的第一个变构抑制剂的发现和命中化合物 4-[2-[5-chloro-1-(diphenylmethyl) 的优化研究。 )-2-甲基-1H-吲哚-3-基]-乙氧基]苯甲酸 (CDIBA)。化合物43n在结构的 4 个不同区域的修饰中进行了优化，并显示出 METTL3-14 复合物的有效酶抑制活性（IC 50 = 2.81 μM)，并通过抑制 m 6 A mRNA 水平在 AML 细胞系中发挥抗增殖作用。43n的抑制机制和结合模式基于变构位点的可逆和非竞争性抑制谱的相互作用以及 METTL3-14 复合物相对于每个亚基酶​​或截短复合酶的选择性。
• Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization
  作者：John C. McKew、Megan A. Foley、Paresh Thakker、Mark L. Behnke、Frank E. Lovering、Fuk-Wah Sum、Steve Tam、Kun Wu、Marina W. H. Shen、Wen Zhang、Mario Gonzalez、Shanghao Liu、Anu Mahadevan、Howard Sard、Soo Peang Khor、James D. Clark

  DOI：10.1021/jm0507882

  日期：2006.1.1

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.