ethyl 3-iodo-5-methoxy-1H-indole-2-carboxylate | 134617-50-8

• 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: ethyl 3-iodo-5-methoxy-1H-indole-2-carboxylate
• CAS: 134617-50-8
• 化学式: C₁₂H₁₂INO₃
• 分子量: 345.137
• InChiKey: IARJKNHXAFLGMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-iodo-5-methoxy-1H-indole-2-carboxylate 在 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 potassium carbonate 、 caesium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 C₂₅H₂₂F₂N₂O₄
  参考文献：
  名称：

  Structure–Activity Relationship (SAR) Development and Discovery of Potent Indole-Based Inhibitors of the Hepatitis C Virus (HCV) NS5B Polymerase

  摘要：

  Starting with the indole-based C-3 pyridone lead HCV polymerase inhibitor 2, extensive SAR studies were performed at different positions of the indole core. The best C-5 groups were found to be compact and nonpolar moieties and that the C-6 attachments were not affecting potency. Limited N-1 benzyl-type substituent studies indicated that the best substitutions were fluoro or methyl groups at 2' or 5' positions of the benzyl group. To improve pharmacokinetic (PK) properties, acylsulfonamides were incorporated as acid isosteres at the C-2 position. Further optimization of the combination at N-1, C-2, C-5, and C-6 resulted in the identification of compound 56, which had an excellent potency in both NS5B enzyme (IC50 = 0.008 mu M) and cell-based replicon (EC50 = 0.02 mu M) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 mu M.h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported.

  DOI：

  10.1021/jm201258k
• 作为产物：
  描述：

  5-甲氧基吲哚-2-甲酸乙酯 在 N-氯代丁二酰亚胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以97%的产率得到ethyl 3-iodo-5-methoxy-1H-indole-2-carboxylate
  参考文献：
  名称：

  通过区域选择性 6-exo-dig 碘内酯化反应合成 Oxazinoindolones 及其反应性

  摘要：

  通过使用区域和立体选择性开发了一种简便构建 3,4-dihydro-10-iodo-3-iodomethylene-[1,4]-oxazino[4,3-a]indol-1-ones 的有效方案碘内酯化反应。随后 3,4-dihydro-10-iodo-3-iodomethylene-[1,4]-oxazino[4,3-a]indol-1-ones 的钯交叉偶联反应很容易得到功能化的 oxazinoindolones。

  DOI：

  10.1002/ejoc.201801167

文献信息

• Axially Chiral<scp>Aryl‐Alkene‐Indole</scp>Framework: A Nascent Member of the Atropisomeric Family and Its Catalytic Asymmetric Construction
  作者：Cong‐Shuai Wang、Tian‐Zhen Li、Si‐Jia Liu、Yu‐Chen Zhang、Shuang Deng、Yinchun Jiao、Feng Shi

  DOI：10.1002/cjoc.202000131

  日期：2020.6

  axially chiral aryl‐alkene‐indole frameworks have been designed, and the first catalytic asymmetric construction of such scaffolds has been established by the strategy of organocatalytic (Z/E)‐selective and enantioselective (4+3) cyclization of 3‐alkynyl‐2‐indolylmethanols with 2‐naphthols or phenols (all >95 : 5 E/Z, up to 98% yield, 97% ee). This reaction also represents the first catalytic asymmetric

  设计了一类新的轴向手性芳基-烯烃-吲哚骨架，并通过3的有机催化（Z / E）选择性和对映选择性（4 + 3）环化策略建立了此类支架的第一个催化不对称结构。带有2-萘酚或苯酚的炔基-2-吲哚基甲醇（均> 95：5 E / Z，产率高达98％，ee高达97％）。该反应也代表了轴向手性烯烃-杂芳基骨架的第一个催化不对称结构，它将为阻转异构体家族增加一个新成员。这种方法不仅在构建轴向手性烯烃-杂芳基骨架方面面临巨大挑战，而且为轴向手性芳基烯烃-吲哚骨架的对映选择性构建提供了强有力的策略。
• Design and biological evaluation of substituted 5,7-dihydro-6<i>H</i>-indolo[2,3-<i>c</i>]quinolin-6-one as novel selective Haspin inhibitors
  作者：Sreenivas Avula、Xudan Peng、Xingfen Lang、Micky Tortorella、Béatrice Josselin、Stéphane Bach、Stephane Bourg、Pascal Bonnet、Frédéric Buron、Sandrine Ruchaud、Sylvain Routier、Cleopatra Neagoie

  DOI：10.1080/14756366.2022.2082419

  日期：2022.12.31

  substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction, and a reduction/lactamization sequence. The inhibitory activity of the 22 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC50 of 1 and 2 nM with selectivity

  摘要 取代吲哚[2,3 - c ]quinolone-6-ones 库被开发为简化的Lamellarin 等排体。在涉及碘化、Suzuki-Miyaura 交叉偶联反应和还原/内酰胺化序列的四步途径序列后，从吲哚合成。评估了 22 种新衍生物对 Haspin 激酶的抑制活性。其中两个具有 1 nM 和 2 nM 的 IC 50，对包括母体激酶 DYRK1A 和 CLK1 在内的 10 种其他激酶具有选择性。最具选择性的化合物还对骨肉瘤 U-2 OS 细胞系产生了非常有趣的细胞作用。
• New C5-Alkylated Indolobenzazepinones Acting as Inhibitors of Tubulin Polymerization: Cytotoxic and Antitumor Activities
  作者：Laurent Keller、Stéphane Beaumont、Jian-Miao Liu、Sylviane Thoret、Jérôme S. Bignon、Joanna Wdzieczak-Bakala、Philippe Dauban、Robert H. Dodd

  DOI：10.1021/jm701466p

  日期：2008.6.1

  A series of 5-alkylindolobenzazepin-7-ones was synthesized by Suzuki coupling between 3-iodoindole-2-carboxylates and the appropriate alpha-alkylbenzylamino o-boronic acids followed by cyclization to the lactam. Derivatives having a linear alkyl chain at C5 were found to be highly cytotoxic to KB cells with IC50 values in the 30-80 nM range. These compounds also inhibited the polymerization of tubulin with IC50's of 1-2 mu M. Compound 4f ((S)-5-ethyl) showed comparable antiproliferative activities (IC50's of 30-70 nM) in a variety of cancer cell lines, cell growth being arrested at the G2/M phase. Compound 4f induced apoptosis in a dose-dependent manner in three different cancer cell lines and was shown to affect cell morphology in a manner consistent with its inhibitory action on tubulin polymerization. Using the experimental model of glioma grafted on the chick chorio-allantoic membrane, local treatment with compound 4f markedly reduced tumor progression.
• Synthesis and evaluation of heterocycle structures as potential inhibitors of Mycobacterium tuberculosis UGM
  作者：Carine Maaliki、Jian Fu、Sydney Villaume、Albertus Viljoen、Clément Raynaud、Sokaina Hammoud、Jérôme Thibonnet、Laurent Kremer、Stéphane P. Vincent、Emilie Thiery

  DOI：10.1016/j.bmc.2020.115579

  日期：2020.7

  In this study, we screen three heterocyclic structures as potential inhibitors of UDP-galactopyranose mutase (UGM), an enzyme involved in the biosynthesis of the cell wall of Mycobacterium tuberculosis. In order to understand the binding mode, docking simulations are performed on the best inhibitors. Their activity on Mycobacterium tuberculosis is also evaluated. This study made it possible to highlight an "oxazepino-indole" structure as a new inhibitor of UGM and of M. tuberculosis growth in vitro.