1-(5-hydroxy-1H-indol-2-yl)ethanone | 1373439-05-4

• 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: 1-(5-hydroxy-1H-indol-2-yl)ethanone
• CAS: 1373439-05-4
• 化学式: C₁₀H₉NO₂
• 分子量: 175.187
• InChiKey: RTHSOZYDJGEATR-UHFFFAOYSA-N

物化性质

• 沸点：
  411.3±25.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(5-hydroxy-1H-indol-2-yl)ethanone 、 5-溴-2-羟基苯并肼 在 溶剂黄146 作用下， 以 丙醇 为溶剂， 以65%的产率得到(E)-5-bromo-2-hydroxy-N'-(1-(5-hydroxy-1H-indol-2-yl)ethylidene)benzohydrazide
  参考文献：
  名称：

  Optimization and structure–activity relationships of a series of potent inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as novel antimicrobial agents

  摘要：

  A novel series of hydrazones were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK has been identified as one of the most highly connected 'hub proteins' in MRSA. PK has been shown to be critical for bacterial survival which makes it a potential target for development of novel antibiotics and the high degree of connectivity implies it should be very sensitive to mutations and thus less able to develop resistance. PK is not unique to bacteria and thus a critical requirement for such a PK inhibitor would be that it does not inhibit the homologous human enzyme(s) at therapeutic concentrations. Several MRSA PK inhibitors (including 8d) were identified using in silico screening combined with enzyme assays and were found to be selective for bacterial enzyme compared to four human PK isoforms (M1, M2, R and L). However these lead compounds did not show significant inhibitory activity for MRSA growth presumably due to poor bacterial cell penetration. Structure-activity relationship (SAR) studies were carried out on 8d and led us to discover more potent compounds with enzyme inhibiting activities in the low nanomolar range and some were found to effectively inhibit bacteria growth in culture with minimum inhibitory concentrations (MIC) as low as 1 mu g/mL. These inhibitors bind in two elongated flat clefts found at the minor interfaces in the homo-tetrameric enzyme complex and the observed SAR is in keeping with the size and electronic constraints of these binding sites. Access to the corresponding sites in the human enzyme is blocked. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.002
• 作为产物：
  描述：

  1-(5-甲氧基-1H-吲哚-2-基)乙酮 在 三溴化硼 、 水 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 以70%的产率得到1-(5-hydroxy-1H-indol-2-yl)ethanone
  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 MÉTHODES ASSOCIÉES

  摘要：

  提供了具有A-C式结构的化合物。提供了这些化合物作为抗生素的用途，包括革兰氏阴性和革兰氏阳性微生物，以及涉及这些化合物的治疗方法和用途。

  公开号：

  WO2012051708A1

文献信息

• [EN] ANTI-BACTERIAL PYRUVATE KINASE MODULATOR COMPOUNDS, COMPOSITIONS, USES, AND METHODS<br/>[FR] COMPOSÉS ANTIBACTÉRIENS MODULATEURS DE LA PYRUVATE KINASE, COMPOSITIONS, UTILISATIONS ET MÉTHODES ASSOCIÉES
  申请人：UNIV BRITISH COLUMBIA

  公开号：WO2012051708A1

  公开（公告）日：2012-04-26

  Compounds having a structure of Formulas A-C are provided. Uses of such compounds as an antibiotic, including both gram-negative and gram-positive micro-organisms, as well as methods of treatment and uses involving such compounds are provided.

  提供了具有A-C式结构的化合物。提供了这些化合物作为抗生素的用途，包括革兰氏阴性和革兰氏阳性微生物，以及涉及这些化合物的治疗方法和用途。
• Novel cc-1065 Analogs and Their Conjugates
  申请人：Beusker Patrick Henry

  公开号：US20110207767A1

  公开（公告）日：2011-08-25

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.
• NOVEL CONJUGATES OF CC-1065 ANALOGS AND BIFUNCTIONAL LINKERS
  申请人：Beusker Patrick Henry

  公开号：US20130224227A1

  公开（公告）日：2013-08-29

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.
• Novel Conjugates of CC-1065 Analogs and Bifunctional Linkers
  申请人：SYNTARGA BV

  公开号：US20170274090A1

  公开（公告）日：2017-09-28

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.
• US9629924B2
  申请人：——

  公开号：US9629924B2

  公开（公告）日：2017-04-25