5-bromo-2-ethynyl-1H-indole | 1572178-30-3

• 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-bromo-2-ethynyl-1H-indole
• CAS: 1572178-30-3
• 化学式: C₁₀H₆BrN
• 分子量: 220.068
• InChiKey: YYKDXIFPDGBUAN-UHFFFAOYSA-N

物化性质

• 沸点：
  358.4±22.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  15.8
• 氢给体数：
  1
• 氢受体数：
  0

反应信息

• 作为产物：
  描述：

  5-bromo-2-iodo-1-(phenylsulfonyl)-1H-indole 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 5-bromo-2-ethynyl-1H-indole
  参考文献：
  名称：

  Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections

  摘要：

  A novel series of bis-indoles derived from naturally occurring marine alkaloid 4 were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK is not only critical for bacterial survival which would make it a target for development of novel antibiotics, but it is reported to be one of the most highly connected 'hub proteins' in MRSA, and thus should be very sensitive to mutations and making it difficult for the bacteria to develop resistance. From the co-crystal structure of cis-3-4-dihydrohamacanthin B (4) bound to S. aureus PK we were able to identify the pharmacophore needed for activity. Consequently, we prepared simple direct linked bis-indoles such as 10b that have similar anti-MRSA activity as compound 4. Structure-activity relationship (SAR) studies were carried out on 10b and led us to discover more potent compounds such as 10c, 10d, 10k and 10m with enzyme inhibiting activities in the low nanomolar range that effectively inhibited the bacteria growth in culture with minimum inhibitory concentrations (MIC) for MRSA as low as 0.5 mu g/ml. Some potent PK inhibitors, such as 10b, exhibited attenuated antibacterial activity and were found to be substrates for an efflux mechanism in S. aureus. Studies comparing a wild type S. aureus with a construct (S. aureus LAC Delta pyk::ErmR) that lacks PK activity confirmed that bactericidal activity of 10d was PK-dependant. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.020

文献信息

• Manganese-Catalyzed C−H Alkynylation: Expedient Peptide Synthesis and Modification
  作者：Zhixiong Ruan、Nicolas Sauermann、Elisabetta Manoni、Lutz Ackermann

  DOI：10.1002/anie.201611118

  日期：2017.3.13

  catalysis manifold enabled C−H couplings with haloalkynes featuring, among others, fluorescent labels, steroids, and amino acids, thereby setting the stage for peptide ligation as well as the efficient molecular assembly of acyclic and cyclic peptides. A plausible catalytic cycle was proposed.

  锰（I）催化的带有有机卤化物的CH炔基化反应在无与伦比的底物范围内发生，从而实现了使用甲硅烷基，芳基，烯基和烷基卤代炔烃进行经济的CH官能化。锰（I）催化歧管的多功能性使CH与卤代炔烃偶合，其特征包括荧光标记，类固醇和氨基酸，从而为肽连接以及无环和环状肽的有效分子组装奠定了基础。提出了合理的催化循环。
• ANTI-BACTERIAL PYRUVATE KINASE MODULATOR COMPOUNDS, COMPOSITIONS, USES AND METHODS
  申请人：SIMON FRASER UNIVERSITY

  公开号：US20170216252A1

  公开（公告）日：2017-08-03

  Compounds of general formula I that are capable of inhibiting bacterial pyruvate kinase and/or bacterial growth. The compounds may find use as antibacterial agents in therapeutic and/or non-therapeutic contexts.
• [EN] ANTI-BACTERIAL PYRUVATE KINASE MODULATOR COMPOUNDS, COMPOSITIONS, USES AND METHODS<br/>[FR] COMPOSÉS ANTIBACTÉRIENS MODULATEURS DE LA PYRUVATE KINASE, COMPOSITIONS, UTILISATIONS ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV FRASER SIMON

  公开号：WO2016004513A1

  公开（公告）日：2016-01-14

  Compounds of general formula I that are capable of inhibiting bacterial pyruvate kinase and/or bacterial growth. The compounds may find use as antibacterial agents in therapeutic and/or non- therapeutic contexts.