3,5-二-(三氟甲基)-联苯-4-羧酸 | 195457-74-0

• 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: 3,5-二-(三氟甲基)-联苯-4-羧酸
• 英文名称: 3',5'‐bis(trifluoromethyl)‐(1,1'‐biphenyl)‐4‐carboxylic acid
• 英文别名: 3',5'-Bis(trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid；4-[3,5-bis(trifluoromethyl)phenyl]benzoic acid
• CAS: 195457-74-0
• 化学式: C₁₅H₈F₆O₂
• 分子量: 334.218
• InChiKey: HIXMMDMXBCYZQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  358.3±42.0 °C(Predicted)
• 密度：
  1.426±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  23
• 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：
  37.3
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 海关编码：
  2916399090

反应信息

• 作为反应物：
  描述：

  3,5-二-(三氟甲基)-联苯-4-羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-[3,5-Bis(trifluoromethyl)phenyl]benzoyl chloride
  参考文献：
  名称：

  Structure–Activity Relationships and Anti-inflammatory Activities of N-Carbamothioylformamide Analogues as MIF Tautomerase Inhibitors

  摘要：

  Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is an attractive therapeutic target for the treatment of inflammatory diseases. In our previous study, 3-[(biphenyl-4-ylcarbonyl)carbamothioyl] amino benzoic acid (compound 1) was discovered as a potent inhibitor of MIF by docking-based virtual screening and bioassays. Here, a series of analogues of compound 1 derived from similarity search and chemical synthesis were evaluated for their MIF tautomerase activities, and their structure activity relationships were then analyzed. The most potent inhibitor (compound 5) with an IC50 of 370 nM strongly suppressed lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-6 in a dose-dependent manner and significantly enhanced the survival rate of mice with LPS-induced endotoxic shock from 0 to 35% at 0.5 mg/kg and to 45% at 1 mg/kg, highlighting the therapeutic potential of the MIF tautomerase inhibition in inflammatory diseases.

  DOI：

  10.1021/acs.jcim.5b00445
• 作为产物：
  描述：

  4-碘苯甲酸 、 3,5-双(三氟甲基)苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 42.5h， 以42%的产率得到3,5-二-(三氟甲基)-联苯-4-羧酸
  参考文献：
  名称：

  A Novel Biphenyl-based Chemotype of Retinoid X Receptor Ligands Enables Subtype and Heterodimer Preferences

  摘要：

  The nuclear retinoid X receptors (RXRs) are key ligand sensing transcription factors that serve as universal nuclear receptor heterodimer partners and are thus involved in numerous physiological processes. Therapeutic targeting of RXRs holds high potential but available RXR activators suffer from limited safety. Selectivity for RXR subtypes or for certain RXR heterodimers are promising strategies for safer RXR modulation. Here, we report systematic structure activity relationship studies on biphenyl carboxylates as new RXR ligand chemotype. We discovered specific structural modifications that enhance potency on RXRs, govern subtype preference, and vary modulation of different RXR heterodimers. Fusion of these structural motifs enabled specific tuning of subtype preferential profiles with markedly improved potency. Our results provide further evidence that RXR subtype selective ligands can be designed and present a novel chemotype of RXR modulators that can be tuned for subtype and heterodimer preferences.

  DOI：

  10.1021/acsmedchemlett.9b00306

文献信息

• NMR-Based Discovery of Lead Inhibitors That Block DNA Binding of the Human Papillomavirus E2 Protein
  作者：Philip J. Hajduk、Jürgen Dinges、Gregory F. Miknis、Megan Merlock、Tim Middleton、Dale J. Kempf、David A. Egan、Karl A. Walter、Terry S. Robins、Suzy B. Shuker、Thomas F. Holzman、Stephen W. Fesik

  DOI：10.1021/jm9703404

  日期：1997.9.1

  The E2 protein is required far the replication of human papillomaviruses (HPVs), which are responsible for anogenital warts and cervical carcinomas, Using an NMR-based screen, we tested compounds for binding to the DNA-binding domain of the HPV-E2 protein. Three classes of compounds were identified which bound to two distinct sites on the protein. Biphenyl and biphenyl ether compounds containing a carboxylic acid bind to a site near the DNA recognition helix and inhibit the binding of E2 to DNA. Benzophenone-containing compounds which lack a carboxylic acid group bind to the beta-barrel formed by the dimer intel face and exhibit negligible effects on the binding of E2 to DNA. Structure-activity relationships from the biphenyl and biphenyl ether compounds were combined to produce a compound [5-(3'-(3 '',5 ''-dichlorophenoxy)phenyl)-2,4-pentadienoic acid] with an IC50 value of approximately 10 mu M. This compound represents a useful lead for the development of antiviral agents that interfere with HPV replication and further illustrates the usefulness of the SAR by NMR method in the drug discovery process.
• PIPERAZINE DERIVATIVES AS MAGL INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3694840B1

  公开（公告）日：2021-08-04