1-(5-(trifluoromethyl)-1H-indol-2-yl)ethan-1-one | 1373439-03-2

• 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-(trifluoromethyl)-1H-indol-2-yl)ethan-1-one
• 英文别名: 1-[5-(trifluoromethyl)-1H-indol-2-yl]ethanone
• CAS: 1373439-03-2
• 化学式: C₁₁H₈F₃NO
• 分子量: 227.186
• InChiKey: CHQBGISMROXJIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  32.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-(trifluoromethyl)-1H-indol-2-yl)ethan-1-one 在 盐酸羟胺 、 sodium acetate 、 nickel(II) acetate tetrahydrate 、 四丁基碘化铵 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 1,3-dimethyl-8-(trifluoromethyl)pyrazino[1,2-a]indole 2oxide
  参考文献：
  名称：

  镍（II）催化2-羰基-1-炔丙基吲哚与羟胺的环氧化物[5 +1]合成水中的吡嗪并[1,2- a ]吲哚-2-氧化物

  摘要：

  通过镍（II）催化的2-羰基-1-炔丙基吲哚的[5 +1]环化反应，开发了一种原子经济实用的方法，可有效合成各种吡嗪并[1,2 - a ]吲哚-2-氧化物。在不使用有机溶剂的情况下与羟胺一起使用。该反应涉及2-羰基-1-炔丙基吲哚与羟胺的初始缩合以提供肟中间体，然后将其进行镍（II）催化的6-exo-dig环化。初步研究表明（n -Bu）4NI用作相转移催化剂，并促进了活性镍（II）物种的形成。更重要的是，镍（II）盐和水中的相转移催化剂可以循环使用七次，并且通过过滤和洗涤方案可以容易地以高收率获得克级可缩放产品。

  DOI：

  10.1021/acs.joc.9b00784
• 作为产物：
  描述：

  4-氨基-3-碘三氟甲苯 在 三乙烯二胺 、 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-(5-(trifluoromethyl)-1H-indol-2-yl)ethan-1-one
  参考文献：
  名称：

  对革兰氏 (-) 细菌具有抗菌活性的新型 MreB 抑制剂

  摘要：

  MreB 是一种存在于杆状细菌中的细胞骨架蛋白，对细菌细胞分裂至关重要且高度保守。由于大多数革兰氏 (-) 细菌需要 MreB 来进行细胞分裂、染色体分离、细胞壁形态发生和细胞极性，因此它是抗菌药物发现的一个有吸引力的目标。由于 MreB 调节与临床使用中的抗生素活性无关，因此对 MreB 抑制剂的获得性耐药性也不太可能。A22 和 CBR-4830 等化合物已知会通过抑制 ATP 酶活性来破坏 MreB 功能。然而，这些化合物的毒性阻碍了评估这些 MreB 抑制剂体内功效的努力。本研究进一步检查了与 CBR-4830 相关的类似物的结构活性，因为它与相对抗生素活性和改进的药物特性有关。这些数据表明某些类似物具有增强的抗生素活性。此外，我们评估了几个有代表性的类似物（9、10、14、26和31 ) 靶向纯化的大肠杆菌MreB ( EcMreB )并抑制其 ATP 酶活性的能力。除14外，所有这些类似物作为

  DOI：

  10.1007/s00044-022-02967-y

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。
• [EN] THERAPEUTIC COMPOUNDS AND METHODS TO TREAT INFECTION<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ET MÉTHODES POUR TRAITER UNE INFECTION
  申请人：UNIV RUTGERS

  公开号：WO2019099402A1

  公开（公告）日：2019-05-23

  Disclosed herein are compounds of formula (I), or a salt thereof and compositions comprising compounds of formula I that exhibit antibacterial activities, when tested alone and/or in combination with a bacterial efflux pump inhibitor. Also disclosed are methods of treating or preventing a bacterial infection in an animal comprising administering to the animal a compound of formula I alone or in combination with the administration of a bacterial efflux pump inhibitor.

  本文披露了化合物的结构式（I）或其盐，以及包含表现出抗菌活性的化合物的组合物的组合物，当单独测试和/或与细菌外排泵抑制剂结合时。还披露了治疗或预防动物细菌感染的方法，包括向动物单独或与细菌外排泵抑制剂的给药结合给动物的结构式（I）的化合物。
• Optimization and structure–activity relationships of a series of potent inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as novel antimicrobial agents
  作者：Nag S. Kumar、Emily A. Amandoron、Artem Cherkasov、B. Brett Finlay、Huansheng Gong、Linda Jackson、Sukhbir Kaur、Tian Lian、Anne Moreau、Christophe Labrière、Neil E. Reiner、Raymond H. See、Natalie C. Strynadka、Lisa Thorson、Edwin W.Y. Wong、Liam Worrall、Roya Zoraghi、Robert N. Young

  DOI：10.1016/j.bmc.2012.10.002

  日期：2012.12

  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.
• THERAPEUTIC COMPOUNDS AND METHODS TO TREAT INFECTION
  申请人：RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

  公开号：US20200325124A1

  公开（公告）日：2020-10-15

  Disclosed herein are compounds of formula (I), or a salt thereof and compositions comprising compounds of formula I that exhibit antibacterial activities, when tested alone and/or in combination with a bacterial efflux pump inhibitor. Also disclosed are methods of treating or preventing a bacterial infection in an animal comprising administering to the animal a compound of formula I alone or in combination with the administration of a bacterial efflux pump inhibitor.