4'-fluoro-2'-methoxybiphenyl-2-carbaldehyde | 1421751-46-3

• 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'-fluoro-2'-methoxybiphenyl-2-carbaldehyde
• 英文别名: 2-(4-fluoro-2-methoxyphenyl)benzaldehyde；4'-Fluoro-2'-methoxy-[1,1'-biphenyl]-2-carbaldehyde
• CAS: 1421751-46-3
• 化学式: C₁₄H₁₁FO₂
• 分子量: 230.239
• InChiKey: BPJPGADDLZKUHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4'-fluoro-2'-methoxybiphenyl-2-carbaldehyde 在 sodium chlorite 、 sodium dihydrogenphosphate 、 三溴化硼 、 叔丁醇 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 27.0h， 生成 3-fluoro-6H-benzo[c]chromen-6-one
  参考文献：
  名称：

  The Fungal Phytotoxin Alternariol 9-Methyl Ether and Some of Its Synthetic Analogues Inhibit the Photosynthetic Electron Transport Chain

  摘要：

  Alternariol and monomethylalternariol are natural phytotoxins produced by some fungal strains, such as Nimbya and Alternaria. These substances confer virulence to phytopathogens, yet no information is available concerning their mode of action. Here we show that in the micromolar range alternariol 9-methyl ether is able to inhibit the electron transport chain (IC50 = 29.1 +/- 6.5 mu M) in isolated spinach chloroplasts. Since its effectiveness is limited by poor solubility in water, several alternariol analogues were synthesized using different aromatic aldehydes. The synthesized 6H-benzo[c]cromen-6-ones, 5H-chromene[4,3-b]pyridin-5-one, and 5H-chromene[4,3-c]pyridin-5-one also showed inhibitory properties, and three 6H-benzo[c]cromen-6-ones were more effective (IC50 =12.8-22.8 mu M) than the lead compound. Their addition to the culture medium of a cyanobacterial model strain was found to inhibit algal growth, with a relative effectiveness that was consistent with their activity in vitro. In contrast, the growth of a nonphotosynthetic plant cell culture was poorly affected. These compounds may represent a novel lead for the development of new active principles targeting photosynthesis.

  DOI：

  10.1021/np4005882
• 作为产物：
  描述：

  邻溴苯甲醛 、 4-氟-2-甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以58%的产率得到4'-fluoro-2'-methoxybiphenyl-2-carbaldehyde
  参考文献：
  名称：

  通过质谱结合分析筛选聚焦的伪静态Hy文库：优化对γ-氨基丁酸转运蛋白的亲和力1

  摘要：

  质谱（MS）结合测定法是一种确定单一药物候选物对所选靶标亲和力的有力工具，最近被证明适用于筛选将动态组合化学反应生成为伪静态时生成的化合物库。筛选针对中枢神经系统中最丰富的γ-氨基丁酸（GABA）转运蛋白γ-氨基丁酸转运蛋白1（GAT1）的小libraries文库，发现了两种由纽福克酸衍生的结合剂，具有亚微摩尔亲和力。从联苯携带的命中作为铅结构开始，本研究的目的是通过筛选由肼10形成的联苯聚焦的假静态文库，发现新型的高亲和力GAT1粘合剂。和36种联苯甲醛11c - al。发现带有2'，4'-二氯联苯残基的Hydrazone 12z是最有效的粘合剂，其纳摩尔亲和力低（p K i = 8.094±0.098）。当合成并评估了代表的稳定的碳氢化合物类似物时，最佳的粘合剂13z再次显示出2'，4'-二氯联苯部分（p K i = 6.930±0.021）。

  DOI：

  10.1021/jm301800j

文献信息

• Combination of MS Binding Assays and affinity selection mass spectrometry for screening of structurally homogenous libraries as exemplified for a focused oxime library addressing the neuronal GABA transporter 1
  作者：Jürgen Gabriel、Georg Höfner、Klaus T. Wanner

  DOI：10.1016/j.ejmech.2020.112598

  日期：2020.11

  resulting oxime library was screened accordingly toward the GABA transporter subtype 1 (GAT1), a drug target for several neurological disorders. After assessing sublibraries’ activities for inhibition of reporter ligand binding, hits in active ones were directly identified. This could be achieved by recording mass transitions for the reporter ligand as well as those predicted for the library components

  这项研究提出了一种有效的筛选方法，该方法基于基于质谱（MS）的结合测定（MS Binding Assays）和亲和力选择质谱（ASMS）的组合，这些筛查被定制用于筛选具有相同质谱碎片模式的结构均质文库。在具有羟胺官能团的乳酸衍生物与醛反应后，针对几种神经系统疾病的药物靶点GABA转运蛋白亚型1（GAT1）相应地筛选所得的肟库。在评估子图书馆抑制报告配体结合的活性后，直接鉴定出活性物质的命中。这可以通过在多反应监测模式下使用三重四极杆质谱仪运行的单个LC-MS / MS中记录报告配体的质量跃迁以及库组分的预测跃迁来实现。可以通过计算IC可靠地确定具有预定义亲和力的匹配来自文库成分和报道分子配体的特定结合浓度的50值。该策略的应用揭示了六个命中，其中两个命中被重新合成以进行进一步的生物学评估。因此，最好的一个在MS结合分析中显示出ap K i为7.38，在[ 3 H] GABA吸收分析中显示出pIC
• Focused Pseudostatic Hydrazone Libraries Screened by Mass Spectrometry Binding Assay: Optimizing Affinities toward γ-Aminobutyric Acid Transporter 1
  作者：Miriam Sindelar、Toni A. Lutz、Marilena Petrera、Klaus T. Wanner

  DOI：10.1021/jm301800j

  日期：2013.2.14

  chosen targets, were recently demonstrated to be suitable for the screening of compound libraries generated with reactions of dynamic combinatorial chemistry when rendering libraries pseudostatic. Screening of small hydrazone libraries targeting γ-aminobutyric acid transporter 1 (GAT1), the most abundant γ-aminobutyric acid (GABA) transporter in the central nervous system, revealed two nipecotic acid derived

  质谱（MS）结合测定法是一种确定单一药物候选物对所选靶标亲和力的有力工具，最近被证明适用于筛选将动态组合化学反应生成为伪静态时生成的化合物库。筛选针对中枢神经系统中最丰富的γ-氨基丁酸（GABA）转运蛋白γ-氨基丁酸转运蛋白1（GAT1）的小libraries文库，发现了两种由纽福克酸衍生的结合剂，具有亚微摩尔亲和力。从联苯携带的命中作为铅结构开始，本研究的目的是通过筛选由肼10形成的联苯聚焦的假静态文库，发现新型的高亲和力GAT1粘合剂。和36种联苯甲醛11c - al。发现带有2'，4'-二氯联苯残基的Hydrazone 12z是最有效的粘合剂，其纳摩尔亲和力低（p K i = 8.094±0.098）。当合成并评估了代表的稳定的碳氢化合物类似物时，最佳的粘合剂13z再次显示出2'，4'-二氯联苯部分（p K i = 6.930±0.021）。
• Novel Allosteric Ligands of γ-Aminobutyric Acid Transporter 1 (GAT1) by MS Based Screening of Pseudostatic Hydrazone Libraries
  作者：Tobias J. Hauke、Thomas Wein、Georg Höfner、Klaus T. Wanner

  DOI：10.1021/acs.jmedchem.8b01602

  日期：2018.11.21

  study describes the screening of dynamic combinatorial libraries based on nipecotic acid as core structure with substituents attached to the 5- instead of the common 1-position for the search of novel inhibitors of the GABA transporter GAT1. The generated pseudostatic hydrazone libraries included a total of nearly 900 compounds and were screened for their binding affinities toward GAT1 in competitive mass

  这项研究描述了筛选以菊苣酸为核心结构的动态组合文库的筛选方法，该结构具有取代基附着在5位而不是常见的1位上，以寻找GABA转运蛋白GAT1的新型抑制剂。生成的伪静态文库总共包含近900种化合物，并在基于竞争质谱（MS）的结合试验中筛选了它们对GAT1的结合亲和力。最高亲和力的腙表征（与顺-构型外消旋- 16gf结合和吸收实验中带有一个5-（1-萘基）呋喃-2-基残基和一个最有效的四原子间隔基）揭示了GAT1的变构相互作用，迄今为止尚无关于其他任何尼克酸衍生物的报道。因此，本文引入的5-取代的庚酸衍生物可以用作研究由GAT1介导的变构调节的GABA转运的有价值的工具，并且还可以作为新一类GAT1抑制剂的起点。
• Identification of Pyrrolidine‐3‐acetic Acid Derived Oximes as Potent Inhibitors of γ‐Aminobutyric Acid Transporter 1 through Library Screening with MS Binding Assays
  作者：Simone K. Huber、Georg Höfner、Klaus T. Wanner

  DOI：10.1002/cmdc.201800556

  日期：2018.12.6

  pyrrolidine‐3‐acetic acid derived oxime libraries were applied to the concept of library screening by MS Binding Assays, as a powerful technique to reveal new potent murine γ‐aminobutyric acid transporter subtype (mGAT1) inhibitors. Library generation was accomplished by condensation of an excess of pyrrolidine‐3‐acetic acid bearing a hydroxylamine unit with various libraries, each composed of eight different

  在这项研究中，将吡咯烷-3-乙酸衍生的肟文库应用于通过MS结合分析进行文库筛选的概念，这是揭示新型有效的鼠类γ-氨基丁酸转运蛋白亚型（mGAT1）抑制剂的强大技术。文库的生成是通过将带有羟胺单元的过量吡咯烷-3-乙酸与各种文库缩合来完成的，每个文库由八个不同的醛组成。肟文库已通过竞争性MS结合测定法进行了筛选，因此，通过解卷积实验进一步研究了活性最高的文库，以鉴定负责观察到的对目标mGAT1活性的单一肟。最终，所有识别出的匹配都经过重新合成，以根据它们的结合亲和力来表征它们，K i = 7.87±0.01）。
• The Fungal Phytotoxin Alternariol 9-Methyl Ether and Some of Its Synthetic Analogues Inhibit the Photosynthetic Electron Transport Chain
  作者：Antonio Jacinto Demuner、Luiz Cláudio Almeida Barbosa、Ana Cristina Mendes Miranda、Guilherme Carvalho Geraldo、Cleiton Moreira da Silva、Samuele Giberti、Michele Bertazzini、Giuseppe Forlani

  DOI：10.1021/np4005882

  日期：2013.12.27

  Alternariol and monomethylalternariol are natural phytotoxins produced by some fungal strains, such as Nimbya and Alternaria. These substances confer virulence to phytopathogens, yet no information is available concerning their mode of action. Here we show that in the micromolar range alternariol 9-methyl ether is able to inhibit the electron transport chain (IC50 = 29.1 +/- 6.5 mu M) in isolated spinach chloroplasts. Since its effectiveness is limited by poor solubility in water, several alternariol analogues were synthesized using different aromatic aldehydes. The synthesized 6H-benzo[c]cromen-6-ones, 5H-chromene[4,3-b]pyridin-5-one, and 5H-chromene[4,3-c]pyridin-5-one also showed inhibitory properties, and three 6H-benzo[c]cromen-6-ones were more effective (IC50 =12.8-22.8 mu M) than the lead compound. Their addition to the culture medium of a cyanobacterial model strain was found to inhibit algal growth, with a relative effectiveness that was consistent with their activity in vitro. In contrast, the growth of a nonphotosynthetic plant cell culture was poorly affected. These compounds may represent a novel lead for the development of new active principles targeting photosynthesis.