methyl (6-chloro-2-methyl-1H-indol-3-yl)oxoacetate | 872675-02-0

• 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: methyl (6-chloro-2-methyl-1H-indol-3-yl)oxoacetate
• 英文别名: methyl 2-(6-chloro-2-methyl-1H-indol-3-yl)-2-oxoacetate
• CAS: 872675-02-0
• 化学式: C₁₂H₁₀ClNO₃
• 分子量: 251.669
• InChiKey: VDPBZKKRRNQFGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (6-chloro-2-methyl-1H-indol-3-yl)oxoacetate 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 sodium hydride 、 三苯基膦 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 17.0h， 生成 methyl 4-[2-[6-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]ethoxy]benzoate
  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：

  Aceton-(m-chlor-phenylhydrazon) 在 三乙胺 、 zinc(II) chloride 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 methyl (6-chloro-2-methyl-1H-indol-3-yl)oxoacetate
  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

• Carbene-Catalyzed Construction of Carbazoles from Enals and 2-Methyl-3-oxoacetate Indoles
  作者：Dehai Liu、Yaru Gao、Jie Huang、Zhenqian Fu、Wei Huang

  DOI：10.1021/acs.joc.8b02532

  日期：2018.11.16

  Direct and rapid construction of carbazoles has been successfully developed via carbene-catalyzed oxidative formal [4 + 2] annulation of enals with 2-methyl-3-oxoacetate indoles. This metal-free reaction features a broad substrate scope, features good functional-group tolerance, proceeds under mild conditions, and can be easily scaled up.

  通过卡宾催化2- [3-氧代乙酸甲酯]的烯醛氧化[4 + 2]正环化，已成功开发了直接快速构建咔唑的方法。这种无金属的反应具有广泛的底物范围，具有良好的官能团耐受性，可在温和条件下进行，并且易于扩大规模。