2-(2,4-二氟苯氧基)丙酸 | 52043-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(2,4-二氟苯氧基)丙酸
• 英文名称: 2-(2,4-difluorophenoxy)propanoic acid
• CAS: 52043-21-7
• 化学式: C₉H₈F₂O₃
• mdl: MFCD03422214
• 分子量: 202.158
• InChiKey: WAKAFGLBHPKARJ-UHFFFAOYSA-N

物化性质

• 沸点：
  301.2±27.0 °C(Predicted)
• 密度：
  1.348±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  2-(2,4-二氟苯氧基)丙酸 、 Methyl 4-aminobut-2-enoate;2,2,2-trifluoroacetic acid 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  一种基于片段的方法来发现半胱氨酸蛋白酶的不可逆共价抑制剂

  摘要：

  报道了一种新的基于片段的药物发现方法，该方法不可逆地将类药物片段束缚在催化半胱氨酸上。我们将亲电试剂连接到 100 个片段上，而亲电试剂的反应性没有显着改变。质谱分析发现了半胱氨酸蛋白酶木瓜蛋白酶的三种非肽抑制剂。鉴定出的化合物显示出不可逆抑制剂的特征。不可逆的束缚系统也显示出特异性：三种鉴定出的木瓜蛋白酶抑制剂不与 UbcH7、USP08 或带有 GST 标签的人类鼻病毒 3C 蛋白酶共价反应。

  DOI：

  10.1021/jm500345q
• 作为产物：
  描述：

  2,4-二氟苯酚 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-(2,4-二氟苯氧基)丙酸
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)

  摘要：

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.011

文献信息

• Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain
  作者：Danielle McShan、Stefan Kathman、Brittiney Lowe、Ziyang Xu、Jennifer Zhan、Alexander Statsyuk、Ifedayo Victor Ogungbe

  DOI：10.1016/j.bmcl.2015.08.074

  日期：2015.10

  Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads. (C) 2015 Elsevier Ltd. All rights reserved.
• A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases
  作者：Stefan G. Kathman、Ziyang Xu、Alexander V. Statsyuk

  DOI：10.1021/jm500345q

  日期：2014.6.12

  reported which irreversibly tethers drug-like fragments to catalytic cysteines. We attached an electrophile to 100 fragments without significant alterations in the reactivity of the electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors of the cysteine protease papain. The identified compounds display the characteristics of irreversible inhibitors. The irreversible tethering system

  报道了一种新的基于片段的药物发现方法，该方法不可逆地将类药物片段束缚在催化半胱氨酸上。我们将亲电试剂连接到 100 个片段上，而亲电试剂的反应性没有显着改变。质谱分析发现了半胱氨酸蛋白酶木瓜蛋白酶的三种非肽抑制剂。鉴定出的化合物显示出不可逆抑制剂的特征。不可逆的束缚系统也显示出特异性：三种鉴定出的木瓜蛋白酶抑制剂不与 UbcH7、USP08 或带有 GST 标签的人类鼻病毒 3C 蛋白酶共价反应。
• Synthesis and structure–activity relationships of novel phenoxyacetamide inhibitors of the Pseudomonas aeruginosa type III secretion system (T3SS)
  作者：John D. Williams、Matthew C. Torhan、Venugopal R. Neelagiri、Carson Brown、Nicholas O. Bowlin、Ming Di、Courtney T. McCarthy、Daniel Aiello、Norton P. Peet、Terry L. Bowlin、Donald T. Moir

  DOI：10.1016/j.bmc.2015.01.011

  日期：2015.3

  The increasing prevalence of drug-resistant bacterial infections is driving the discovery and development not only of new antibiotics, but also of inhibitors of virulence factors that are crucial for in vivo pathogenicity. One such virulence factor is the type III secretion system (T3SS), which plays a critical role in the establishment and dissemination of Pseudomonas aeruginosa infections. We have recently described the discovery and characterization of a series of inhibitors of P. aeruginosa T3SS based on a phenoxyacetamide scaffold. To better characterize the factors involved in potent T3SS inhibition, we have conducted a systematic exploration of this structure, revealing several highly responsive structure-activity relationships indicative of interaction with a specific target. Most of the structural features contributing to potency were additive, and combination of those features produced optimized inhibitors with IC50 values <1 mu M. (C) 2015 Elsevier Ltd. All rights reserved.