1-(Benzenesulfonyl)-6-bromo-2-(bromomethyl)indole | 1572178-40-5

• 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: 1-(Benzenesulfonyl)-6-bromo-2-(bromomethyl)indole
• CAS: 1572178-40-5
• 化学式: C₁₅H₁₁Br₂NO₂S
• 分子量: 429.132
• InChiKey: ZFMQGVJHKNUCLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(Benzenesulfonyl)-6-bromo-2-(bromomethyl)indole 在 吡啶 、 lithium aluminium tetrahydride 、 rhodium(II) perfluorobutyrate dimer 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 、 苯 为溶剂， 反应 44.83h， 生成 2-((6’-bromo-5-chloro-1H,1‘H-[2,2’-biindol]-6-yl)oxy)ethyl methanesulfonate
  参考文献：
  名称：

  [EN] ANTIBIOTIC COMPOUNDS, PHARMACEUTICAL FORMULATIONS THEREOF AND METHODS AND USES THEREFOR
  [FR] COMPOSÉS ANTIBIOTIQUES, LEURS FORMULATIONS PHARMACEUTIQUES, AINSI QUE PROCÉDÉS ASSOCIÉS ET UTILISATIONS ASSOCIÉES

  摘要：

  本发明涉及式(I)的化合物，其中G1至G8如本文所定义。这些化合物是PK抑制剂，因此代表了治疗病原体感染的新方法，包括多药耐药病原体。本文披露了式(I)的化合物，包括含有式(I)的药物组合物以及它们在抗微生物感染治疗中的应用。

  公开号：

  WO2017075694A1
• 作为产物：
  描述：

  6-溴-1-苯基磺酰基-1H-吲哚 在 三溴化磷 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 1-(Benzenesulfonyl)-6-bromo-2-(bromomethyl)indole
  参考文献：
  名称：

  [EN] ANTI-BACTERIAL PYRUVATE KINASE MODULATOR COMPOUNDS, COMPOSITIONS, USES AND METHODS
  [FR] COMPOSÉS ANTIBACTÉRIENS MODULATEURS DE LA PYRUVATE KINASE, COMPOSITIONS, UTILISATIONS ET PROCÉDÉS ASSOCIÉS

  摘要：

  公开号：

  WO2016004513A8

文献信息

• Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections
  作者：Nag S. Kumar、Edie M. Dullaghan、B. Brett Finlay、Huansheng Gong、Neil E. Reiner、J. Jon Paul Selvam、Lisa M. Thorson、Sara Campbell、Nicholas Vitko、Anthony R. Richardson、Roya Zoraghi、Robert N. Young

  DOI：10.1016/j.bmc.2014.01.020

  日期：2014.3

  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.
• 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.