sodium 4-fluorophenoxide | 371-35-7

• 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: sodium 4-fluorophenoxide
• 英文别名: sodium 4-fluorophenolate；sodium p-fluorophenoxide；sodium;4-fluorophenolate
• CAS: 371-35-7
• 化学式: C₆H₄FO*Na
• 分子量: 134.085
• InChiKey: FENGEGUDMXHOBU-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  23.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2908199090

反应信息

• 作为反应物：
  描述：

  sodium 4-fluorophenoxide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 生成 (3S,4S)-3-[(1R)-2-(4-fluorophenoxy)-1-hydroxyethyl]-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)azetidin-2-one
  参考文献：
  名称：

  (−)-SCH 57939: synthesis and pharmacological properties of a potent, metabolically stable cholesterol absorption inhibitor

  摘要：

  Previous SAR studies of C-3 side chain modified analogs of (-)-SCH 48461,(1,3,4) as well as information concerning the metabolic stability this series, enabled us to design a cholesterol absorption inhibitor (i.e., (-) 2a, SCH 57939) with tenfold higher potency and greatly enhanced metabolic stability. The synthesis and pharmacological profile, including the role of relative stereochemistry at both the C3 and 1' positions in determining the SAR of these compounds, will be discussed. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00365-4
• 作为产物：
  描述：

  4-氟苯酚 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以87%的产率得到sodium 4-fluorophenoxide
  参考文献：
  名称：

  带有双（μ-氧代）双铜（III）物种的2-氟酚盐的选择性正羟基加氢脱氟

  摘要：

  双（μ-氧代）双铜（III）物种[Cu III 2（μ-O）2（m-XYL MeAN）] 2+（1）促进2-氟酚盐的亲电子邻羟基化-脱氟，得到相应的儿茶酚，反应不是accomplishable用（η 2：η 2 -O 2）亚铜（II）络合物。同位素标记研究表明，进入的氧原子源自bis（μ-oxo）单元。在分子内竞争中，与其他邻位取代基（例如氯或溴）选择性发生邻羟基化-脱氟。

  DOI：

  10.1002/anie.201405060
• 作为试剂：
  描述：

  (Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine 在 三正丁胺 、 2,6-二叔丁基-4-甲基苯酚 、 sodium 4-fluorophenoxide 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  (−)-SCH 57939: synthesis and pharmacological properties of a potent, metabolically stable cholesterol absorption inhibitor

  摘要：

  Previous SAR studies of C-3 side chain modified analogs of (-)-SCH 48461,(1,3,4) as well as information concerning the metabolic stability this series, enabled us to design a cholesterol absorption inhibitor (i.e., (-) 2a, SCH 57939) with tenfold higher potency and greatly enhanced metabolic stability. The synthesis and pharmacological profile, including the role of relative stereochemistry at both the C3 and 1' positions in determining the SAR of these compounds, will be discussed. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00365-4

文献信息

• Subsupercritical Water Generated by Inductive Heating Inside Flow Reactors Facilitates the Claisen Rearrangement
  作者：Andreas Kirschning、Mona Oltmanns

  DOI：10.1055/s-0040-1705945

  日期：2020.12

  O-allylated phenols, including fluorine-modified phenols, is facilitated in aqueous media at high temperatures and pressures under flow conditions, as opposed to organic solvents. The O-allylation of phenols can be coupled with the Claisen rearrangement in an integrated flow system. Publication History Received: 14 August 2020 Accepted after revision: 16 September 2020 Publication Date: 27 October 2020

  摘要 与有机溶剂相反，在水性介质中，高温和高压下，流动条件下，缺电子的O-烯丙基化酚（包括氟改性的酚）的Claisen重排容易进行。苯酚的O-烯丙基化可以与集成流系统中的Claisen重排结合。 出版历史 收到：2020年8月14日 修订后接受：2020年9月16日 发布日期： 2020年10月27日（在线） ©2020年。Thieme。版权所有 Georg Thieme Verlag KGRüdigerstraße14，70469斯图加特，德国
• Design of PAP-1, a Selective Small Molecule Kv1.3 Blocker, for the Suppression of Effector Memory T Cells in Autoimmune Diseases
  作者：Alexander Schmitz、Ananthakrishnan Sankaranarayanan、Philippe Azam、Kristina Schmidt-Lassen、Daniel Homerick、Wolfram Hänsel、Heike Wulff

  DOI：10.1124/mol.105.015669

  日期：2005.11

  The lymphocyte K+ channel Kv1.3 constitutes an attractive pharmacological target for the selective suppression of terminally differentiated effector memory T (TEM) cells in T cell-mediated autoimmune diseases, such as multiple sclerosis and type 1 diabetes. Unfortunately, none of the existing small-molecule Kv1.3 blockers is selective, and many of them, such as correolide, 4-phenyl-4-[3-(methoxyphenyl)-3-oxo-2-azapropyl]cyclohexanone, and our own compound Psora-4 inhibit the cardiac K+ channel Kv1.5. By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern. The most potent and “drug-like” compound of this series, 5-(4-phenoxybutoxy)psoralen (PAP-1), blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels. PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats. PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators.

  淋巴细胞K+通道Kv1.3是选择性抑制T细胞介导的自身免疫性疾病（如多发性硬化症和1型糖尿病）中终末分化效应记忆T（TEM）细胞的有吸引力的药理学靶点。不幸的是，目前存在的所有小分子Kv1.3阻断剂均不具备选择性，其中许多如柯里奥利德、4-苯基-4-[3-(甲氧苯基)-3-酮-2-氮杂丙基]环己酮以及我们自己的化合物Psora-4均可抑制心脏K+通道Kv1.5。通过结合传统药物化学和全细胞膜片钳技术进一步探索Psora-4的构效关系，我们鉴定了一系列新的苯氧烷氧基补骨脂素，它们对Kv1.3的选择性比Kv1.5高2至50倍，具体取决于其取代模式。这一系列化合物中，最具有强效和“类药物”性质的化合物为5-(4-苯氧基丁氧基)补骨脂素（PAP-1），它以使用依赖性方式阻断Kv1.3，Hill系数为2，EC50为2 nM，通过优先结合通道的C型失活态。PAP-1对Kv1.5的选择性为23倍，对其他Kv1家族通道的选择性为33至125倍，对Kv2.1、Kv3.1、Kv3.2、Kv4.2、HERG、钙激活K+通道、Na+、Ca2+及Cl-通道的选择性为500至7000倍。PAP-1无细胞毒性或光毒性，Ames试验呈阴性，对细胞色素P450依赖性酶的影响仅在微摩尔浓度下显现。PAP-1能强效抑制人TEM细胞的增殖并抑制大鼠中的迟发型超敏反应（一种TEM细胞介导的反应）。因此，PAP-1及其若干衍生物构成了探索Kv1.3作为免疫抑制靶点的新工具，并有可能开发成口服可用的免疫调节剂。
• O2 Activation and Selective Phenolate ortho Hydroxylation by an Unsymmetric Dicopper μ-η1:η1-Peroxido Complex
  作者：Isaac Garcia-Bosch、Anna Company、Jonathan R. Frisch、Miquel Torrent-Sucarrat、Mar Cardellach、Ilaria Gamba、Mireia Güell、Luigi Casella、Lawrence Que、Xavi Ribas、Josep M. Luis、Miquel Costas

  DOI：10.1002/anie.200906749

  日期：2010.3.22

  Unusual reactivity: A novel unsymmetric dicopper complex gives rise to the unsymmetric species 1‐O2 having a μ‐η1:η1‐O2 binding mode and reactivity patterns not previously observed for symmetric analogues. It is unreactive in oxygen atom transfer reactions, but it can selectively bind phenolate and mediate its ortho hydroxylation, thereby demonstrating a conceptually different tyrosinase model with

  不寻常的反应性：一种新的不对称二铜络合物产生了不对称物质1 -O 2，其具有 μ - η 1 :η 1 -O 2结合模式和以前未观察到的对称类似物的反应模式。它在氧原子转移反应中不反应，但它可以选择性地结合苯酚并介导其邻位 羟基化，从而展示了一种概念上不同的酪氨酸酶模型，具有出色的选择性。
• Synthesis and Biological Activity of 11-(4-(Cinnamyl)-1-piperazinyl)-6,11-dihydrodibenz(b,e)oxepin Derivatives, Potential Agents for the Treatment of Cerebrovascular Disorders.
  作者：Mikio KUROKAWA、Fuminori SATO、Yoshinobu MASUDA、Takayuki YOSHIDA、Yuko OCHI、Kayoko ZUSHI、Iwao FUJIWARA、Shunsuke NARUTO、Hitoshi UNO、Jun-ichi MATSUMOTO

  DOI：10.1248/cpb.39.2564

  日期：——

  A series of 11-[4-(cinnamyl)-1-piperazinyl]-6, 11-dihydrodibenz[b, e]oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6, 11-dihydrodibenz[b, e]oxepin-11-yl)-4-(3-phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities.

  合成了一系列11-[4-（肉桂基）-1-哌嗪基]-6，11-二氢二苯并[b，e]氧芴及其相关化合物，并评价了它们对完全缺血、常压缺氧、脂质过氧化和惊厥的保护活性。通过对这一系列化合物的构效关系研究，发现了（E）-1-（3-氟-6，11-二氢二苯并[b，e]氧芑-11-基）-4-（3-苯基-2-丙烯基）哌嗪二马来酸盐（50），AJ-3941，它具有最适合的联合药理活性。
• Strongly Directing Substituents in the Radical Arylation of Substituted Benzenes
  作者：Josefa Hofmann、Timothy Clark、Markus R. Heinrich

  DOI：10.1021/acs.joc.6b01840

  日期：2016.10.21

  radical arylation reactions has grown rapidly in recent years, poor regioselectivities and the need to use a large excess of the radical-accepting arene have hindered their application to substituted benzenes. We now describe experimental and computational investigations into the substituent effects that lead to regioselective addition based on the recent discovery of anilines as outstanding substrates

  尽管近年来人们对自由基芳基化反应的普遍兴趣迅速增长，但区域选择性差，以及需要使用大量过量的能接受自由基的芳烃阻碍了它们在取代苯中的应用。现在我们基于对苯胺作为自由基芳基化的杰出底物的最新发现，描述对导致区域选择性加成的取代基效应的实验和计算研究。