benzyl 3-fluoro-4-hydroxybenzoate | 172463-78-4

• 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: benzyl 3-fluoro-4-hydroxybenzoate
• 英文别名: Benzyl 3-fluoro-4-hydroxybenzoate
• CAS: 172463-78-4
• 化学式: C₁₄H₁₁FO₃
• 分子量: 246.238
• InChiKey: VPZREBLZUSEFTC-UHFFFAOYSA-N

物化性质

• 熔点：
  89-93 °C(Solv: hexane (110-54-3); toluene (108-88-3))
• 沸点：
  385.2±32.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 3-fluoro-4-hydroxybenzoate 在 吡啶 、 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 4-cyano-3-fluorophenyl 4-(4-pentylbenzoyloxy)-3-fluorobenzoate
  参考文献：
  名称：

  Synthesis of Fluorosubstituted Three Ring Esters and Their Dielectric Properties

  摘要：

  Laterally substituted by fluorine atoms 4-cyanophenyl 4-(4-pentylbenzoyloxy)-benzoates have been prepared and their phase transition temperatures, enthalpies and dielectric properties upon frequency were evaluated. The novel compounds exhibit a broad range of nematic mesophase, large positive dielectric anisotropy changing sign at low frequency. They are convenient components of LC mixtures for dual frequency addressing devices.

  DOI：

  10.1080/15421400902817361
• 作为产物：
  描述：

  4-溴-2-氟苯甲醚 在 氢碘酸 、 乙酸酐 、 magnesium 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 benzyl 3-fluoro-4-hydroxybenzoate
  参考文献：
  名称：

  Synthesis of Fluorosubstituted Three Ring Esters and Their Dielectric Properties

  摘要：

  Laterally substituted by fluorine atoms 4-cyanophenyl 4-(4-pentylbenzoyloxy)-benzoates have been prepared and their phase transition temperatures, enthalpies and dielectric properties upon frequency were evaluated. The novel compounds exhibit a broad range of nematic mesophase, large positive dielectric anisotropy changing sign at low frequency. They are convenient components of LC mixtures for dual frequency addressing devices.

  DOI：

  10.1080/15421400902817361

文献信息

• DIACYLETHYLENEDIAMINE COMPOUND
  申请人：Kawano Tomoaki

  公开号：US20120046292A1

  公开（公告）日：2012-02-23

  [Problem] A compound which is useful as an anti-obesity agent is provided. [Means for Solution] The present inventors have investigated a compound having a DGAT1 inhibitory action, which is promising as an active ingredient of a pharmaceutical composition for treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases, and as a result, they have found that the diacylethylenediamine compound of the present invention has an excellent DGAT1 inhibitory action, thereby completing the present invention. That is, the diacylethylenediamine compound of the present invention has a DGAT1 inhibitory action, and can be therefore used as an agent for preventing and/or treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases.

  提供一种作为抗肥胖剂的化合物。现发明人调查了一种具有DGAT1抑制作用的化合物，该化合物有望成为治疗肥胖、2型糖尿病、脂肪肝以及与这些疾病相关的疾病的药物组合物的有效成分，并且他们发现了本发明的二酰乙二胺化合物具有出色的DGAT1抑制作用，从而完成了本发明。也就是说，本发明的二酰乙二胺化合物具有DGAT1抑制作用，因此可用作预防和/或治疗肥胖、2型糖尿病、脂肪肝以及与这些疾病相关的药物。
• A Novel Pan-Negative-Gating Modulator of K_Ca2/3 Channels, Fluoro-Di-Benzoate, RA-2, Inhibits Endothelium-Derived Hyperpolarization–Type Relaxation in Coronary Artery and Produces Bradycardia In Vivo
  作者：Aida Oliván-Viguera、Marta Sofía Valero、Nicole Coleman、Brandon M. Brown、Celia Laría、María Divina Murillo、José A. Gálvez、María D. Díaz-de-Villegas、Heike Wulff、Ramón Badorrey、Ralf Köhler

  DOI：10.1124/mol.114.095745

  日期：2015.2

  Small/intermediate conductance KCa channels (KCa2/3) are Ca2+/calmodulin regulated K+ channels that produce membrane hyperpolarization and shape neurologic, epithelial, cardiovascular, and immunologic functions. Moreover, they emerged as therapeutic targets to treat cardiovascular disease, chronic inflammation, and some cancers. Here, we aimed to generate a new pharmacophore for negative-gating modulation of KCa2/3 channels. We synthesized a series of mono- and dibenzoates and identified three dibenzoates [1,3-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate) (RA-2), 1,2-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate), and 1,4-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate)] with inhibitory efficacy as determined by patch clamp. Among them, RA-2 was the most drug-like and inhibited human KCa3.1 with an IC50 of 17 nM and all three human KCa2 subtypes with similar potencies. RA-2 at 100 nM right-shifted the KCa3.1 concentration-response curve for Ca2+ activation. The positive-gating modulator naphtho[1,2- d ]thiazol-2-ylamine (SKA-31) reversed channel inhibition at nanomolar RA-2 concentrations. RA-2 had no considerable blocking effects on distantly related large-conductance KCa1.1, Kv1.2/1.3, Kv7.4, hERG, or inwardly rectifying K+ channels. In isometric myography on porcine coronary arteries, RA-2 inhibited bradykinin-induced endothelium-derived hyperpolarization (EDH)–type relaxation in U46619-precontracted rings. Blood pressure telemetry in mice showed that intraperitoneal application of RA-2 (≤100 mg/kg) did not increase blood pressure or cause gross behavioral deficits. However, RA-2 decreased heart rate by ≈145 beats per minute, which was not seen in KCa3.1−/− mice. In conclusion, we identified the KCa2/3–negative-gating modulator, RA-2, as a new pharmacophore with nanomolar potency. RA-2 may be of use to generate structurally new types of negative-gating modulators that could help to define the physiologic and pathomechanistic roles of KCa2/3 in the vasculature, central nervous system, and during inflammation in vivo.

  小/中等导电性KCa通道（KCa2/3）是由Ca2+/钙调蛋白调控的K+通道，能够引起膜超极化，从而影响神经、上皮、心血管和免疫功能。此外，它们被作为治疗心血管疾病、慢性炎症和某些癌症的治疗靶点。在此，我们的目标是为KCa2/3通道的负门控调节生成一个新的药效团。我们合成了一系列单和二苯酸酯，并确定了三种具有抑制效力的二苯酸酯[1,3-苯二亚甲基双(3-氟-4-羟基苯酸酯)（RA-2），1,2-苯二亚甲基双(3-氟-4-羟基苯酸酯)和1,4-苯二亚甲基双(3-氟-4-羟基苯酸酯)]，其抑制效能通过膜片钳测试确定。其中，RA-2是最具药物相似性的，IC50为17 nM，能够抑制人类KCa3.1，并以相似的效力抑制所有三种人类KCa2亚型。RA-2在100 nM时使KCa3.1的Ca2+激活浓度-反应曲线向右移动。正门控调节剂萘并[1,2-d]噻唑-2-氨基（SKA-31）在纳摩尔RA-2浓度下逆转了通道抑制。RA-2对远相关的大导电性KCa1.1、Kv1.2/1.3、Kv7.4、hERG或内向整流K+通道无显著阻断作用。在猪冠状动脉的等张肌肉测定中，RA-2抑制了由缓激肽引起的内皮源超极化（EDH）型松弛。在小鼠的血压遥测中，腹腔注射RA-2（≤100 mg/kg）未增加血压或造成明显的行为缺陷。然而，RA-2降低了心率约145次每分钟，而这在KCa3.1−/−小鼠中未见到。总之，我们鉴定了负门控调节剂KCa2/3，RA-2，作为一种具有纳摩尔效力的新药效团。RA-2可能有助于生成结构上新类型的负门控调节剂，这有助于阐明KCa2/3在血管、中央神经系统及炎症过程中的生理和病理机制作用。
• 10.1016/j.tetlet.2024.155104
  作者：Majumder, Utpal、Zhu, Xiaojie、Du, Hong、Li, Xiangyi、Miao, Guobin、Postema, Maarten、Wang, John、Bao, Xingfeng、Zheng, Wanjun

  DOI：10.1016/j.tetlet.2024.155104

  日期：——

  medicinal chemistry efforts, an efficient and reliable synthesis of amide isosteres of Schweinfurthin G, where the central olefinic linkage between C and D rings has been replaced with amide bond, is described. The approach relied on a copper mediated coupling reaction of organo-magnesium species with allylic chloride is easily amenable to rapid analoging to generate amide based isosteres of the natural

  为了加速药物化学工作，描述了 Schweinfurthin G 酰胺等排体的高效、可靠合成，其中 C 和 D 环之间的中心烯键已被酰胺键取代。该方法依赖于有机镁物质与烯丙基氯的铜介导的偶联反应，易于快速模拟以生成基于酰胺的天然产物等排物。
• [EN] DIACYLETHYLENEDIAMINE COMPOUND<br/>[FR] COMPOSÉ DIACYLÉTHYLÈNEDIAMINE
  申请人：ASTELLAS PHARMA INC

  公开号：WO2010122968A1

  公开（公告）日：2010-10-28

  【課題】抗肥満薬として有用な化合物を提供する。 【解決手段】本発明者らは、肥満、II型糖尿病、脂肪肝、及びそれらに起因する周辺疾患の治療用医薬組成物の有効成分として有望な、DGAT1阻害作用を有する化合物について検討し、本発明のジアシルエチレンジアミン化合物が優れたDGAT1阻害作用を有することを確認し、本発明を完成した。即ち、本発明のジアシルエチレンジアミン化合物はDGAT1阻害作用を有し、肥満、II型糖尿病、脂肪肝、及びそれらの周辺疾患の予防及び／又は治療剤として使用しうる。
• Synthesis of Fluorosubstituted Three Ring Esters and Their Dielectric Properties
  作者：Dorota Ziobro、Jerzy Dziaduszek、Marek Filipowicz、Roman Dąbrowski、Joanna Czub、Stanisław Urban

  DOI：10.1080/15421400902817361

  日期：2009.5.29

  Laterally substituted by fluorine atoms 4-cyanophenyl 4-(4-pentylbenzoyloxy)-benzoates have been prepared and their phase transition temperatures, enthalpies and dielectric properties upon frequency were evaluated. The novel compounds exhibit a broad range of nematic mesophase, large positive dielectric anisotropy changing sign at low frequency. They are convenient components of LC mixtures for dual frequency addressing devices.