8-quinolylmethylphosphonic acid | 75355-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-quinolylmethylphosphonic acid
• 英文别名: [(quinolin-8-yl)methyl]phosphonic acid；quinolin-8-ylmethylphosphonic acid
• CAS: 75355-39-4
• 化学式: C₁₀H₁₀NO₃P
• 分子量: 223.168
• InChiKey: JEAIVEQRSHHAIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  8-溴甲基喹啉 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 8-quinolylmethylphosphonic acid
  参考文献：
  名称：

  Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases

  摘要：

  Gram-negative pathogens expressing serine beta-lactamases (SBLs) and metallo-beta-lactamases (MBLs), especially those with carbapenemase activity, threaten the clinical utility of almost all beta-lactam antibiotics. Here we describe the discovery of a heteroaryl phosphonate scaffold that exhibits noncovalent cross-class inhibition of representative carbapenemases, specifically the SBL KPC-2 and the MBLs NDM-1 and VIM-2. The most potent lead, compound 16, exhibited low nM to low mu M inhibition of KPC-2, NDM-1, and VIM-2. Compound 16 potentiated imipenem efficacy against resistant clinical and laboratory bacterial strains expressing carbapene- mases while showing some cytotoxicity toward human HEK293T cells only at concentrations above 100 mu g/mL. Complex structures with KPC-2, NDM-1, and VIM-2 demonstrate how these inhibitors achieve high binding affinity to both enzyme classes. These findings provide a structurally and mechanistically new scaffold for drug discovery targeting multidrug resistant Gram-negative pathogens and more generally highlight the active site features of carbapenemases that can be leveraged for lead discovery.

  DOI：

  10.1021/acs.jmedchem.9b00728

文献信息

• [EN] BETA-LACTAMASE INHIBITORS, FORMULATIONS, AND USES THEREOF<br/>[FR] INHIBITEURS DE BÊTA-LACTAMASES, FORMULATIONS ET UTILISATIONS CORRESPONDANTES
  申请人：UNIV SOUTH FLORIDA

  公开号：WO2017156458A1

  公开（公告）日：2017-09-14

  Provided herein are heterocyclic compounds and pharmaceutical formulations that can be used to treat bacterial infections. Also provided herein are methods of making and using the heterocyclic compounds and pharmaceutical formulations.

  本文提供了可以用于治疗细菌感染的杂环化合物和制药配方。同时，本文还提供了制备和使用这些杂环化合物和制药配方的方法。
• Beta-lactamase inhibitors, formulations, and uses thereof
  申请人：UNIVERSITY OF SOUTH FLORIDA

  公开号：US10543221B2

  公开（公告）日：2020-01-28

  Provided herein are heterocyclic compounds and pharmaceutical formulations that can be used to treat bacterial infections. Also provided herein are methods of making and using the heterocyclic compounds and pharmaceutical formulations.

  本文提供了可用于治疗细菌感染的杂环化合物和药物制剂。本文还提供了制造和使用这些杂环化合物和药物制剂的方法。
• Jagodic, V.; Bozic, B.; Tusek-Bozic, Lj., Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 685 - 688
  作者：Jagodic, V.、Bozic, B.、Tusek-Bozic, Lj.、Herak, M. J.

  DOI：——

  日期：——
• JAGODIC V.; BOZIC B.; TUSEK-BOZIC L.; HERAK M. J., J. HETEROCYCL. CHEM., 1980, 17, NO 4, 685-688
  作者：JAGODIC V.、 BOZIC B.、 TUSEK-BOZIC L.、 HERAK M. J.

  DOI：——

  日期：——
• NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN THE TREATMENT OF TISSUE FIBROSIS
  申请人：Sunshine Lake Pharma Co., Ltd.

  公开号：EP3083584B1

  公开（公告）日：2018-02-21