3-(2-azidoethyl)-5-fluoro-1H-indole | 1258297-02-7

• 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: 3-(2-azidoethyl)-5-fluoro-1H-indole
• CAS: 1258297-02-7
• 化学式: C₁₀H₉FN₄
• 分子量: 204.207
• InChiKey: CYXUZBIJYNTCOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  30.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-azidoethyl)-5-fluoro-1H-indole 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 生成 5-氟色胺
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

  摘要：

  Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.

  DOI：

  10.1021/jm1009988
• 作为产物：
  描述：

  5-fluoro-3-(2-hydroxyethyl)-1H-indole methanesulfonate 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以80%的产率得到3-(2-azidoethyl)-5-fluoro-1H-indole
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

  摘要：

  Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.

  DOI：

  10.1021/jm1009988

文献信息

• Construction of Vicinal All-Carbon Quaternary Stereocenters by Catalytic Asymmetric Alkylation Reaction of 3-Bromooxindoles with 3-Substituted Indoles: Total Synthesis of (+)-Perophoramidine
  作者：Hailong Zhang、Liang Hong、Hong Kang、Rui Wang

  DOI：10.1021/ja408336v

  日期：2013.9.25

  Highly congested vicinal all-carbon quaternary stereocenters were generated via catalytic asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted indoles. These catalytic reactions proceeded in excellent yields with a broad scope on either reaction partner, and with outstanding diastereo- and enantiocontrol. The newly developed method led to the total synthesis of (+)-perophoramidine

  高度拥挤的邻位全碳四元立体中心是通过 3-溴吲哚与 3-取代吲哚的催化不对称烷基化反应产生的。这些催化反应以优异的产率进行，在任一反应伙伴上都有广泛的范围，并且具有出色的非对映和对映控制。新开发的方法以高效的方式全合成了 (+)-perophorimidine。
• Exploiting translational stalling peptides in an effort to extend azithromycin interaction within the prokaryotic ribosome nascent peptide exit tunnel
  作者：Arren Z. Washington、Subhasish Tapadar、Alex George、Adegboyega K. Oyelere

  DOI：10.1016/j.bmc.2015.04.078

  日期：2015.8

  The ribosome is the primary protein synthesis machine in the cell and is a target for treatment of a variety of diseases including bacterial infection and cancer. The ribosomal peptide exit tunnel, the route of egress for the nascent peptide, is an inviting site for drug design. Toward a rational engagement of the nascent peptide components for the design of small molecule inhibitors of ribosome function, we designed and disclosed herein a set of N-10 indole functionalized azithromycin analogs. The indole moiety of these compounds is designed to mimic the translation stalling interaction of SecM W155 side-chain with the prokaryotic (Escherichia coli) ribosome A751 residue. Many of these N-10 functionalized compounds have enhanced translation inhibition activities against E. coli ribosome relative to azithromycin while a subset inhibited the growth of representative susceptible bacteria strains to about the same extent as azithromycin. Moreover, the inclusion of bovine serum in the bacterial growth media enhanced the anti-bacterial potency of the N-10 functionalized azithromycin analogs by as high as 10-fold. Published by Elsevier Ltd.
• Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors
  作者：Jalal Soubhye、Martine Prévost、Pierre Van Antwerpen、Karim Zouaoui Boudjeltia、Alexandre Rousseau、Paul G. Furtmüller、Christian Obinger、Michel Vanhaeverbeek、Jean Ducobu、Jean Nève、Michel Gelbcke、Franc¸ois Dufrasne

  DOI：10.1021/jm1009988

  日期：2010.12.23

  Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.