2-methoxy-4-(trifluoromethyl)phenol | 1027888-79-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-methoxy-4-(trifluoromethyl)phenol
• CAS: 1027888-79-4
• 化学式: C₈H₇F₃O₂
• 分子量: 192.138
• InChiKey: WULGVCJGJHHILR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methoxy-4-(trifluoromethyl)phenol 在 四丁基硫酸氢铵 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 2-[1-[2-hydroxy-3-[2-methoxy-4-(trifluoromethyl)phenoxy]propyl]piperidin-4-yl]-3H-isoindol-1-one
  参考文献：
  名称：

  Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors

  摘要：

  A novel class of Na(V)1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse Na(V)1.7 inhibitory activities with fair subtype selectivity over Na(V)1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.005
• 作为产物：
  描述：

  4-氟-3-甲氧基三氟甲苯 在 palladium on activated charcoal 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-methoxy-4-(trifluoromethyl)phenol
  参考文献：
  名称：

  Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors

  摘要：

  A novel class of Na(V)1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse Na(V)1.7 inhibitory activities with fair subtype selectivity over Na(V)1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.005

文献信息

• [EN] MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 2<br/>[FR] MODULATEURS DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE 2
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2021155196A1

  公开（公告）日：2021-08-05

  The present application provides a compound of Formula: or a pharmaceutically acceptable salt thereof, wherein ring B, L1, ring A, L2, n, R1, R2, R3, R4, and X1 are as described herein. Pharmaceutical compositions comprising the compound, as well as the methods of making and using the compound, are also provided.

  本申请提供了一种化合物的公式：或其药用可接受的盐，其中环B、L1、环A、L2、n、R1、R2、R3、R4和X1如本文所述。还提供了包含该化合物的药物组合物，以及制造和使用该化合物的方法。
• 硝基咪唑类化合物及其制备方法和用途
  申请人：南京长澳医药科技有限公司

  公开号：CN112300192B

  公开（公告）日：2023-08-11

  本发明公开了一种新型硝基咪唑类化合物及其制备方法和用途。所述硝基咪唑类化合物具有下述通式(I)：
• Design and synthesis of morpholine derivatives. SAR for dual serotonin &amp; noradrenaline reuptake inhibition
  作者：Paul V. Fish、Christopher Deur、Xinmin Gan、Keri Greene、David Hoople、Malcolm Mackenny、Kimberly S. Para、Keith Reeves、Thomas Ryckmans、Cory Stiff、Alan Stobie、Florian Wakenhut、Gavin A. Whitlock

  DOI：10.1016/j.bmcl.2008.03.050

  日期：2008.4

  Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key step. Structure-activity relationships established that serotonin and noradrenaline

  单一对映异构体（SS）和（RR）2-[（（苯氧基）（苯基）甲基]吗啉衍生物5、8-23是单胺再摄取的抑制剂。使用对映体选择性合成方法制备目标化合物，该方法采用高特异性酶催化的外消旋4-苄基吗啉-2-羧酸正丁酯（26）作为关键步骤。建立了构效关系，认为5-羟色胺和去甲肾上腺素的再摄取抑制是立体化学和芳基/芳氧基取代的功能。因此，所有选择性SRI，选择性NRI和双重SNRI均已确定。选择其中一种化合物，即强效和选择性双重SNRI（SS）-5a作为进一步临床前评估的候选药物。
• Synthesis of Chiral Esters via Asymmetric Wolff Rearrangement Reaction
  作者：Jing Meng、Wei-Wei Ding、Zhi-Yong Han

  DOI：10.1021/acs.orglett.9b03227

  日期：2019.12.20

  The first asymmetric Wolff rearrangement reaction that directly converts α-diazoketones into broadly useful chiral α,α-disubstituted carboxylic esters with high enantioselectivities (up to 97.5:2.5 er) is reported. The cascade reaction proceeds through the seamless combination of visible-light-induced formation of the ketene intermediate and asymmetric ketene esterification using a readily available

  报道了第一个不对称的Wolff重排反应，该反应将α-二氮酮直接转化为具有高对映选择性（高达97.5：2.5 er）的广泛使用的手性α，α-二取代的羧酸酯。级联反应通过使用可见的苯并四咪唑型催化剂将可见光诱导的乙烯酮中间体的形成与不对称的乙烯酮酯化反应无缝结合而进行。
• Molecular Basis for Selective Serotonin Reuptake Inhibition by the Antidepressant Agent Fluoxetine (Prozac)
  作者：Jacob Andersen、Nicolai Stuhr-Hansen、Linda Grønborg Zachariassen、Heidi Koldsø、Birgit Schiøtt、Kristian Strømgaard、Anders S. Kristensen

  DOI：10.1124/mol.113.091249

  日期：2014.5

  Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model compared with the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity.

  血清素转运体（SERT）的抑制剂被广泛用作抗抑郁剂，但其抑制活性和对密切相关的去甲肾上腺素转运体（NET）的选择性背后的结构机制尚不清楚。在这里，我们结合化学、生物学和计算方法，解析了典型抗抑郁药物氟西汀（Prozac；礼来制药，印第安纳波利斯）在SERT中的高亲和力识别以及对NET的选择性的分子基础。我们发现氟西汀结合在人体SERT的中心底物位点，这与最近的LeuBAT X射线晶体结构保持一致，LeuBAT是细菌氨基酸转运蛋白LeuT的工程化单胺样版本。然而，在我们支持的实验模型中，氟西汀的结合方向与LeuBAT结构相比是反向的，这强调了在将细菌转运体的晶体结构发现推及到与人类相关的转运体时需要进行谨慎的实验验证。我们发现氟西汀和其NET选择性结构同源物nisoxetine的选择性由转运体不同区域的氨基酸残基控制，这表明在SERT和NET中对结构相似化合物具有复杂的选择性识别机制。我们的发现为抗抑郁剂的SERT/NET选择性的分子基础提供了重要的新信息，并首次评估了LeuBAT作为人类转运体中抗抑郁药结合模型系统的潜力，这对于未来基于结构的抗抑郁药物开发具有重要意义，特别是对转运体选择性的细致调控。