[1,1-Biphenyl]-3-carboxylicacid,4-hydroxy-,hydrazide(9CI) | 1373439-19-0

• 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: [1,1-Biphenyl]-3-carboxylicacid,4-hydroxy-,hydrazide(9CI)
• 英文别名: 2-hydroxy-5-phenylbenzohydrazide
• CAS: 1373439-19-0
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: ILMVMDVXZUGUGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-乙酰基吲哚 、 [1,1-Biphenyl]-3-carboxylicacid,4-hydroxy-,hydrazide(9CI) 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以22%的产率得到4-hydroxy-N'-[(1E)-1-(1H-indol-2-yl)ethylidene]-1,1'-biphenyl-3-carbohydrazide
  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
• 作为产物：
  描述：

  4-羟基-1,1'-联苯-3-羧酸甲酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 [1,1-Biphenyl]-3-carboxylicacid,4-hydroxy-,hydrazide(9CI)
  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。
• 1,2,4-Triazole-3-thione analogues with an arylakyl group at position 4 as metallo-β-lactamase inhibitors
  作者：Laurent Gavara、Federica Verdirosa、Laurent Sevaille、Alice Legru、Giuseppina Corsica、Lionel Nauton、Paola Sandra Mercuri、Filomena Sannio、Filomena De Luca、Margot Hadjadj、Giulia Cerboni、Yen Vo Hoang、Patricia Licznar-Fajardo、Moreno Galleni、Jean-Denis Docquier、Jean-François Hernandez

  DOI：10.1016/j.bmc.2022.116964

  日期：2022.10

  group of various lengths up to a butyl chain were also synthesized. Some compounds in both sub-series were micromolar to submicromolar inhibitors of tested VIM-type MBLs. A few of them were broad-spectrum inhibitors, as they showed significant inhibitory activity on NDM-1 and, to a lesser extent, IMP-1. Among these, several inhibitors were able to significantly reduce the meropenem MIC on VIM-1- and VIM-4-

  金属-β-内酰胺酶 (MBL) 对公众健康构成越来越严重的威胁，因为它们在全球范围内在相关机会性革兰氏阴性病原体中的流行率增加。MBL 可有效灭活广泛使用且最有价值的 β-内酰胺类抗生素，例如氧亚氨基头孢菌素（头孢曲松、头孢他啶）和最后的碳青霉烯类。迄今为止，还没有 MBL 抑制剂被批准用于治疗应用。我们正在开发以 1,2,4-三唑-3-硫酮支架为原始锌配体特征的抑制剂，并且已经报道了一些有前途的系列。在这里，我们介绍了一系列新化合物的合成和评估，这些化合物的特征是在三唑环的 4 位存在芳基烷基取代基。烷基链主要是乙烯，但也合成了一些不含烷基或具有不同长度的烷基（直至丁基链）的化合物。两个子系列中的一些化合物是测试的 VIM 型 MBL 的微摩尔到亚微摩尔抑制剂。其中一些是广谱抑制剂，因为它们对 NDM-1 和 IMP-1 表现出显着的抑制活性。其中，几种抑制剂能够将美罗培南对产生 VIM-1
• 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.