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.