Acetyl 2-fluorobenzoate | 1622838-73-6

• 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: Acetyl 2-fluorobenzoate
• 英文别名: acetyl 2-fluorobenzoate
• CAS: 1622838-73-6
• 化学式: C₉H₇FO₃
• 分子量: 182.151
• InChiKey: SSTKKOMWSGVZSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  22β-[(3-methyl-1-oxo-2-butenyl)oxy]-3β-hydroxyolean-12-en-28-oic acid 、 Acetyl 2-fluorobenzoate 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 3β-(2-fluorobenzoyloxy)-22β-senecioyloxy-olean-12-en-28-oic acid
  参考文献：
  名称：

  Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation

  摘要：

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.

  DOI：

  10.1016/j.bmcl.2014.06.068
• 作为产物：
  描述：

  乙酰氯 、 邻氟苯甲酸 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 生成 Acetyl 2-fluorobenzoate
  参考文献：
  名称：

  Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation

  摘要：

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.

  DOI：

  10.1016/j.bmcl.2014.06.068

文献信息

• Synthesis, characterization and biological action of optically active isomers of floxacins
  申请人：Somberg Charin John

  公开号：US20060111369A1

  公开（公告）日：2006-05-25

  Disclosed herein is the method for synthesis and separation of enantiospecific isomers of floxacins. These isomers can be used to study the antibacterial action, as well as cardiac effects, such as arrhythmogenic activity, QT internal prolongation and dispersion, and Ikr inhibition in humans. A method for the identification of chiral isolates of the floxacins that are devoid or possess less QT prolonging action and thus cause less arthropathy especially of the Torsades de pointes variety. Also disclosed are methods for assaying these isomeric compounds present in the biological fluids.

  本文揭示了一种合成和分离氟喹诺酮的对映异构体的方法。这些异构体可用于研究抗菌作用，以及对心脏的影响，如心律失常活性，QT间期延长和离散度，以及在人体内对Ikr的抑制作用。本文还揭示了一种识别氟喹诺酮的手性分离物，这些分离物没有或具有较少的QT延长作用，因此引起的关节病变特别是扭转性室性心动过速较少。此外，还揭示了检测生物体液中这些异构化合物的方法。
• [EN] SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTION OF OPTICALLY ACTIVE ISOMERS OF FLOXACINS<br/>[FR] SYNTHESE, CARACTERISATION ET ACTION BIOLOGIQUE D'ISOMERES ACTIFS SUR LE PLAN OPTIQUE DE FLOXACINES
  申请人：SOMBERG JOHN CHARIN

  公开号：WO2006052264A2

  公开（公告）日：2006-05-18

  [EN] Disclosed herein is the method for synthesis and separation of enantiospecific isomers of floxacins. These isomers can be used to study the antibacterial action, as well as cardiac effects, such as arrhythmogenic activity, QT internal prolongation and dispersion, and Ikr inhibition in humans. A method for the identification of chiral isolates of the floxacins that are devoid or possess less QT prolonging action and thus cause less arthropathy especially of the Torsades de pointes variety. Also disclosed are methods for assaying these isomeric compounds present in the biological fluids.
  [FR] L'invention concerne un procédé destiné à la synthèse et à la séparation d'isomères enantio-spécifiques de floxacines. Ces isomères peuvent être utilisés pour l'étude de l'action antibactérienne, ainsi que des effets cardiaques, tels que l'activité arythmogène, la prolongation et la dispersion interne de QT et l'inhibition de Ikr chez des êtres humains. L'invention concerne également un procédé d'identification d'isolats chiraux des floxacines exempts d'action de prolongation de QT ou possédant une action de prolongation de QT inférieure et engendrant, par conséquent, moins d'arthropathie, notamment de la variété des Torsades de pointes. L'invention concerne également des procédés permettant d'analyser ces composés isomères présents dans les fluides biologiques.
• Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation
  作者：Monika、Ankesh Sharma、Sharad Kumar Suthar、Vaibhav Aggarwal、Hong Boon Lee、Manu Sharma

  DOI：10.1016/j.bmcl.2014.06.068

  日期：2014.8

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.