3-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]propanamide | 1148046-99-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]propanamide
• CAS: 1148046-99-4
• 化学式: C₂₇H₂₁F₃N₄O
• 分子量: 474.485
• InChiKey: SPVLUERLPVVWIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4,4,4-三氟-1-(2-菲基)-1,3-丁烷二酮 在 盐酸 、 platinum(IV) oxide 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， 生成 3-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]propanamide
  参考文献：
  名称：

  Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

  摘要：

  Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.018

文献信息

• A simple protein histidine kinase activity assay for high-throughput inhibitor screening
  作者：Donghee Lee、Yunmi Lee、Son Hye Shin、Su Min Choi、Shin Hyeon Lee、Seonghun Jeong、Soojin Jang、Jung-Min Kee

  DOI：10.1016/j.bioorg.2022.106232

  日期：2023.1

  current HK activity assays based on the quantification of autophosphorylated HKs are hampered by the instability of the phosphohistidine (pHis) product, rendering them ill-suited for high-throughput screenings. To address this challenge, we developed a simple HK activity assay using readily available reagents, which we have termed AUDECY (AUtophosphorylation-DEphosphorylation CYcle assay). Instead of

  细菌双组分系统 (TCS) 通常由传感器组氨酸激酶 (HK) 和反应调节剂 (RR) 组成，已被研究作为有吸引力的抗菌药物靶点。不幸的是，当前基于自磷酸化 HK 量化的 HK 活性测定受到磷酸组氨酸 (pHis) 产品的不稳定性的阻碍，使它们不适合高通量筛选。为了应对这一挑战，我们使用现成的试剂开发了一种简单的 HK 活性测定，我们将其称为 AUDECY（自磷酸化-去磷酸化循环测定）。我们没有试图保存脆弱的 pHis，而是故意用 pHis 特异性磷酸酶分解它，以构成一个类似 ATPase 的循环，以便于进行比色测量。大肠杆菌EnvZ 和耐万古霉素粪肠球菌(VRE) VanS的高通量抑制剂筛选，其中组氨酸激酶活性很难用常规方法检测到。通过筛选，我们确定了 OSU-03012，一种有效的 VanS HK 抑制剂，它使 VRE 对万古霉素敏感，突出了 AUDECY 在 HK 抑制剂发现中的潜力。
• Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus
  作者：Hao-Chieh Chiu、Su-Lin Lee、Naval Kapuriya、Dasheng Wang、Yi-Ru Chen、Sung-Liang Yu、Samuel K. Kulp、Lee-Jene Teng、Ching-Shih Chen

  DOI：10.1016/j.bmc.2012.06.018

  日期：2012.8

  Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA. (C) 2012 Elsevier Ltd. All rights reserved.