N-(2,4-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide | 634189-16-5

• 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: N-(2,4-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
• 英文别名: N-[2,4-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide
• CAS: 634189-16-5
• 化学式: C₁₅H₈ClF₆NO₂
• 分子量: 383.677
• InChiKey: GVJQYFCJRPNYTJ-UHFFFAOYSA-N

物化性质

• 沸点：
  330.7±42.0 °C(Predicted)
• 密度：
  1.561±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氯代水杨酸 、 2,4-双(三氟甲基)苯胺 在 三氯化磷 作用下， 以 甲苯 为溶剂， 以51%的产率得到N-(2,4-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
  参考文献：
  名称：

  IMD-0354 的结构功能研究鉴定出高活性粘菌素佐剂。

  摘要：

  由多重耐药（MDR）细菌，特别是革兰氏阴性菌引起的感染是一个不断升级的全球健康威胁。临床医生常常被迫使用最后手段抗生素粘菌素。然而，粘菌素耐药性正变得越来越普遍，导致可能出现多重耐药革兰氏阴性菌感染没有治疗选择的情况。开发规避细菌耐药机制的佐剂是开发新抗生素的一种有前途的正交方法。我们最近披露，已知的 IKK-β 抑制剂 IMD-0354 可有效抑制几种革兰氏阴性菌株的粘菌素耐药性。在这项研究中，我们探索了 IMD-0354 支架与粘菌素耐药性抑制之间的构效关系 (SAR)，并鉴定了几种比母体对鲍曼不动杆菌和肺炎克雷伯菌高度粘菌素耐药菌株具有更有效活性的化合物。

  DOI：

  10.1002/cmdc.201900560

文献信息

• Structure–Function Studies on IMD‐0354 Identifies Highly Active Colistin Adjuvants
  作者：Ansley M. Nemeth、Akash K. Basak、Alexander W. Weig、Santiana A. Marrujo、William T. Barker、Leigh A. Jania、Tyler A. Hendricks、Ashley E. Sullivan、Patrick M. O'Connor、Roberta J. Melander、Beverly H. Koller、Christian Melander

  DOI：10.1002/cmdc.201900560

  日期：2020.1.17

  disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-negative strains. In this study, we explore the structure-activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin-resistant strains of Acinetobacter baumannii and Klebsiella

  由多重耐药（MDR）细菌，特别是革兰氏阴性菌引起的感染是一个不断升级的全球健康威胁。临床医生常常被迫使用最后手段抗生素粘菌素。然而，粘菌素耐药性正变得越来越普遍，导致可能出现多重耐药革兰氏阴性菌感染没有治疗选择的情况。开发规避细菌耐药机制的佐剂是开发新抗生素的一种有前途的正交方法。我们最近披露，已知的 IKK-β 抑制剂 IMD-0354 可有效抑制几种革兰氏阴性菌株的粘菌素耐药性。在这项研究中，我们探索了 IMD-0354 支架与粘菌素耐药性抑制之间的构效关系 (SAR)，并鉴定了几种比母体对鲍曼不动杆菌和肺炎克雷伯菌高度粘菌素耐药菌株具有更有效活性的化合物。
• Nf-kb activation inhibitors
  申请人：Muto Susumu

  公开号：US20060089395A1

  公开（公告）日：2006-04-27

  A medicament having inhibitory activity against NF-κB activation which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is circle around (1)} a fused polycyclic heteroaryl group wherein the ring which binds directly to —CONH— group in the formula (I) is a benzene ring, circle around (2)} unsubstituted thiazol-2-yl group, or circle around (3)} unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —CONH-E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —CONH-E wherein E has the same meaning as that defined above.

  一种药物具有抑制NF-κB活化作用，其包括以下通式(I)所表示的化合物或其药学上可接受的盐、水合物和溶剂化物作为活性成分，其中A代表氢原子或乙酰基，E代表2,5-二取代或3,5-二取代苯基或单环或融合的多环杂环芳基，其可以被取代，但在所述杂环芳基是圆圈(1)}在公式(I)中直接结合—CONH—基团的环为苯环的融合多环杂环芳基，圆圈(2)}未取代的噻唑-2-基团，或者圆圈(3)}未取代的苯并噻唑-2-基团时，不包括该化合物，环Z代表一个芳香烃，除了由公式—O-A所表示的基团外，它也可以有一个或多个取代基，其中A具有与上述定义相同的含义，公式—CONH-E所表示的基团E具有与上述定义相同的含义。
• Inhibitors against activation of NF-kappaB
  申请人：MUTO Susumu

  公开号：US20080311074A1

  公开（公告）日：2008-12-18

  A method of inhibiting NF-κB activation in a mammal including a human, which comprises the step of administering an effective dose of a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof:

  一种抑制哺乳动物（包括人类）中NF-κB激活的方法，包括以下步骤：给予所选物质的有效剂量，所选物质选自以下组合：一种由下列通式（I）表示的化合物及其药理学上可接受的盐、水合物和溶剂化物。
• NF-KB ACTIVATION INHIBITORS
  申请人：Institute of Medicinal Molecular Design, Inc.

  公开号：EP1535609A1

  公开（公告）日：2005-06-01

  A medicament having inhibitory activity against NF-κB activation which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is ① a fused polycyclic heteroaryl group wherein the ring which binds directly to ―CONH― group in the formula (I) is a benzene ring, ② unsubstituted thiazol-2-yl group, or ③ unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula -CONH-E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula ― CONH―E wherein E has the same meaning as that defined above.

  一种对 NF-κB 活化具有抑制活性的药物，其活性成分包括选自由下通式 (I) 所代表的化合物及其药理学上可接受的盐、其水合物和其溶液组成的组中的一种物质： 其中 A 代表氢原子或乙酰基、 E 代表 2,5-二取代或 3,5-二取代苯基，或可被取代的单环或融合多环杂芳基、但上述杂芳基为①融合多环杂芳基的化合物除外，其中式（I）中直接与-CONH-基团结合的环为苯环、②未取代的噻唑-2-基团或③未取代的苯并噻唑-2-基团、 环 Z 代表除式-O-A（其中 A 的含义与上述定义相同）所代表的基团和式-CONH-E（其中 E 的含义与上述定义相同）所代表的基团外还可具有一个或多个取代基的炔类，或除式-O-A（其中 A 的含义与上述定义相同）所代表的基团和式-CONH-E（其中 E 的含义与上述定义相同）所代表的基团外还可具有一个或多个取代基的杂芳环。
• EP1535609
  申请人：——

  公开号：——

  公开（公告）日：——