4-((3,5-dimethylpiperidin-1-yl)sulfonyl)-N-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)benzamide

• 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: 4-((3,5-dimethylpiperidin-1-yl)sulfonyl)-N-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)benzamide
• 英文别名: 4-[(3R,5S)-3,5-dimethylpiperidin-1-yl]sulfonyl-N-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]benzamide
• 化学式: C₂₂H₂₃FN₄O₄S
• 分子量: 458.513
• InChiKey: BDAMVSRRCJKIGV-GASCZTMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (3S,5R)-3,5-dimethylpiperidine 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4-((3,5-dimethylpiperidin-1-yl)sulfonyl)-N-(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl)benzamide
  参考文献：
  名称：

  有效抑制金黄色葡萄球菌脂磷壁酸生物合成的抗菌小分子。

  摘要：

  抗生素耐药性的上升，特别是在金黄色葡萄球菌中，以及由于多重耐药细菌导致的死亡率增加已得到了充分的证明。对新的化学实体和/或鉴定用于抗菌药物开发的新靶标的需求很高。脂磷壁酸（LTA）是一种附着在膜上的阴离子聚合物，对许多革兰氏阳性细菌的生长和毒力很重要，人们对LTA生物合成抑制剂的发现也很感兴趣。迄今为止，仅描述了少数LTA生物合成抑制剂对金黄色葡萄球菌具有中等（MIC = 5.34μgmL-1）到低（MIC = 1024μgmL-1）的活性。在本文中，我们描述了有效抑制金黄色葡萄球菌LTA生物合成，表现出令人印象深刻的抗菌活性（MIC低至0的新化合物）的鉴定。25μgmL-1）的耐甲氧西林金黄色葡萄球菌（MRSA）。在类似的体外测定条件下，这些化合物的抗MRSA活性比万古霉素高4倍，比利奈唑胺高8倍。

  DOI：

  10.1002/cmdc.201900053

文献信息

• [EN] BENZAMIDE ANTIBACTERIAL AGENTS<br/>[FR] AGENTS ANTIBACTÉRIENS À BASE DE BENZAMIDE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2019199496A1

  公开（公告）日：2019-10-17

  The present invention generally relates to compounds as a new antibiotic to treat various infections, including infections caused by methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Clostridioides difficile. Pharmaceutical compositions and methods for treating those diseases are within the scope of this invention.

  本发明通常涉及化合物作为一种新的抗生素，用于治疗各种感染，包括由耐甲氧西林金黄色葡萄球菌、耐万古霉素和万古霉素耐药金黄色葡萄球菌、万古霉素耐药粪肠球菌和难辨梭菌引起的感染。制药组合物和治疗这些疾病的方法属于本发明的范围。
• N-(1,3,4-oxadiazol-2-yl)benzamide analogs, bacteriostatic agents against methicillin- and vancomycin-resistant bacteria
  作者：Clement Opoku-Temeng、George A. Naclerio、Haroon Mohammad、Neetu Dayal、Nader S. Abutaleb、Mohamed N. Seleem、Herman O. Sintim

  DOI：10.1016/j.ejmech.2018.06.023

  日期：2018.7

  Various reports of multidrug-resistant bacteria that are immune to all available FDA-approved drugs demand the development of novel chemical scaffolds as antibiotics. From screening a chemical library, we identified compounds with antibacterial activity. The most potent compounds, F6-5 and F6, inhibited growth of various drug-resistant Gram-positive bacterial pathogens at concentrations ranging from 1 mu g/mL to 2 mu g/mL. Both compounds were active against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin-resistant S. aureus (VISA and VRSA respectively) and vancomycin-resistant Enterococcus faecalis (VRE). Resistance generation experiments revealed that MRSA could develop resistance to the antibiotic ciprofloxacin but not to F6. Excitingly, F6 was found to be non-toxic against mammalian cells. In a mouse skin wound infection model, F6 was equipotent to the antibiotic fusidic acid in reducing MRSA burden. (C) 2018 Elsevier Masson SAS. All rights reserved.
• BENZAMIDE ANTIBACTERIAL AGENTS
  申请人：Purdue Research Foundation

  公开号：US20210047316A1

  公开（公告）日：2021-02-18

  The present invention generally relates to compounds as a new antibiotic to treat various infections, including infections caused by methicillin-resistant Staphylococcus aureus , vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus faecalis and Clostridioides difficile . Pharmaceutical compositions and methods for treating those diseases are within the scope of this invention.
• Antibacterial Small Molecules That Potently Inhibit <i>Staphylococcus aureus</i> Lipoteichoic Acid Biosynthesis
  作者：George A. Naclerio、Caroline W. Karanja、Clement Opoku‐Temeng、Herman O. Sintim

  DOI：10.1002/cmdc.201900053

  日期：2019.5.17

  The rise of antibiotic resistance, especially in Staphylococcus aureus, and the increasing death rate due to multiresistant bacteria have been well documented. The need for new chemical entities and/or the identification of novel targets for antibacterial drug development is high. Lipoteichoic acid (LTA), a membrane-attached anionic polymer, is important for the growth and virulence of many Gram-positive

  抗生素耐药性的上升，特别是在金黄色葡萄球菌中，以及由于多重耐药细菌导致的死亡率增加已得到了充分的证明。对新的化学实体和/或鉴定用于抗菌药物开发的新靶标的需求很高。脂磷壁酸（LTA）是一种附着在膜上的阴离子聚合物，对许多革兰氏阳性细菌的生长和毒力很重要，人们对LTA生物合成抑制剂的发现也很感兴趣。迄今为止，仅描述了少数LTA生物合成抑制剂对金黄色葡萄球菌具有中等（MIC = 5.34μgmL-1）到低（MIC = 1024μgmL-1）的活性。在本文中，我们描述了有效抑制金黄色葡萄球菌LTA生物合成，表现出令人印象深刻的抗菌活性（MIC低至0的新化合物）的鉴定。25μgmL-1）的耐甲氧西林金黄色葡萄球菌（MRSA）。在类似的体外测定条件下，这些化合物的抗MRSA活性比万古霉素高4倍，比利奈唑胺高8倍。