{[双（4-氟苯基）甲基]硫基}乙酸 | 90212-81-0

• 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: {[双（4-氟苯基）甲基]硫基}乙酸
• 英文名称: 2-((bis(4-fluorophenyl)methyl)-thio)acetic acid
• 英文别名: 2-((bis(4-fluorophenyl)methyl)thio)acetic acid；2-[bis-(4-fluorophenyl)methylthio]acetic acid；2-(bis(4-fluorophenyl)methylthio)acetic acid；HOSdpF；{[Bis(4-fluorophenyl)methyl]thio}acetic acid；2-[bis(4-fluorophenyl)methylsulfanyl]acetic acid
• CAS: 90212-81-0
• 化学式: C₁₅H₁₂F₂O₂S
• mdl: MFCD05270835
• 分子量: 294.322
• InChiKey: AKBHXBCMSOZXPR-UHFFFAOYSA-N

物化性质

• 沸点：
  410.6±45.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {[双（4-氟苯基）甲基]硫基}乙酸 在 lithium aluminium tetrahydride 、 硫酸 、 双氧水 作用下， 以 四氢呋喃 、 甲醇 、 水 、 溶剂黄146 、 异丙醇 、 丙酮 为溶剂， 反应 4.0h， 生成 N-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)-3-phenylpropan-1-amine oxalate
  参考文献：
  名称：

  Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

  摘要：

  2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (+/-)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (+/-)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen. Halogen substitution of the diphenyl rings of (+/-)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT and SEAT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT.

  DOI：

  10.1021/jm401754x
• 作为产物：
  描述：

  4,4'-二氟二苯甲醇 、 巯基乙酸 在 三氟乙酸 作用下， 以2.8 g的产率得到{[双（4-氟苯基）甲基]硫基}乙酸
  参考文献：
  名称：

  新型系列莫达非尼（2-[（（二苯甲基）亚磺酰基]乙酰胺）类似物在单胺转运蛋白上的结构-活性关系。

  摘要：

  合成了一系列莫达非尼（1）类似物，其中1）将对卤代取代基添加到芳环上，2）除去亚砜官能团，3）伯酰胺基被仲和叔酰胺和胺取代，得到研究这些化学修饰对DAT，SERT和NET结合的影响。另外，将（+/-）-莫达非尼（1），其R-和S-对映异构体及其对氯亚磺酰基乙酰胺类似物（5c）对小鼠的运动刺激作用与可卡因进行了比较。

  DOI：

  10.1021/ml1002025

文献信息

• Asymmetric Oxidation Synthesis of Modafinil Acid by Use of a Recyclable Chiral‐at‐Metal Complex
  作者：Zheng‐Zheng Li、Su‐Yang Yao、A‐Hao Wen、Bao‐Hui Ye

  DOI：10.1002/ejic.201500617

  日期：2015.9

  Δ/Λ-3. Diastereoselective oxidation of the thioether complexes in situ produced the corresponding sulfoxide complexes rac-1a, Δ/Λ-1a, rac-2a, Δ/Λ-2a, rac-3a, and Δ/Λ-3a. The configuration at the metal center in each case is stable during the coordination and oxidation reactions, and dictates the chirality of the sulfoxide ligand in the oxidation process. The chiral modafinil acids were obtained with ee

  手性莫达非尼酸及其具有高对映体过量的类似物的对映选择性氧化合成已通过手性金属策略开发。用适当的前手性硫醚配体处理钌配合物顺式-[Ru(bpy)2Cl2]或Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2（bpy是2,2'-联吡啶），得到硫醚络合物 rac-1、Δ/Λ-1、rac-2、Δ/Λ-2、rac-3 和 Δ/Λ-3。硫醚复合物的非对映选择性氧化产生相应的亚砜复合物 rac-1a、Δ/Λ-1a、rac-2a、Δ/Λ-2a、rac-3a 和 Δ/Λ-3a。在每种情况下，金属中心的构型在配位和氧化反应过程中都是稳定的，并决定了氧化过程中亚砜配体的手性。在 TFA/MeCN 存在下从相应的亚砜复合物中去除后，获得的手性莫达非尼酸的 ee 值大于 98%。此外，手性钌前体 Δ/Λ-[Ru(bpy)2(MeCN)2](PF6)2 是可回收和可重复使用的，完全保留了构型。
• SARs at the Monoamine Transporters for a Novel Series of Modafinil Analogues
  作者：Jianjing Cao、Thomas E. Prisinzano、Oluyomi M. Okunola、Theresa Kopajtic、Matthew Shook、Jonathan L. Katz、Amy Hauck Newman

  DOI：10.1021/ml1002025

  日期：2011.1.13

  A series of modafinil (1) analogues was synthesized wherein 1) para-halo-substitutents were added to the aryl rings, 2) the sulfoxide function was removed, and 3) the primary amide group was replaced with secondary and tertiary amides and amines to investigate the effects of these chemical modifications on DAT, SERT and NET binding. In addition, the locomotor-stimulant effects in mice of (+/-)-modafinil

  合成了一系列莫达非尼（1）类似物，其中1）将对卤代取代基添加到芳环上，2）除去亚砜官能团，3）伯酰胺基被仲和叔酰胺和胺取代，得到研究这些化学修饰对DAT，SERT和NET结合的影响。另外，将（+/-）-莫达非尼（1），其R-和S-对映异构体及其对氯亚磺酰基乙酰胺类似物（5c）对小鼠的运动刺激作用与可卡因进行了比较。
• POTENT AND SELECTIVE INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF
  申请人：THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH AND HUMAN SERVICE

  公开号：US20160009644A1

  公开（公告）日：2016-01-14

  Disclosed herein are bisarylmethylthioacetamides and bisarylmethylthioethylamines useful as inhibitors of monoamine transporters. The compounds are potent and/or selective inhibitors of dopamine (DA), serotonin (5-HT), and/or norepinephrine (NE) reuptake via their respective transporters, DAT, SERT and NET. Also disclosed are methods for eliciting a wake-promoting or cognitive or attention enhancing effect and for treating substance use disorders, attention deficit (hyperactivity) disorder, depressive disorders, bipolar disorder or other neuropsychiatric disorders sleep disorders or cognitive impairment using the compounds.

  本文揭示了双芳基甲硫基乙酰胺和双芳基甲硫基乙胺作为单胺转运体抑制剂的用途。这些化合物是通过它们各自的转运体DAT、SERT和NET对多巴胺（DA）、5-羟色胺（5-HT）和/或去甲肾上腺素（NE）的再摄取具有强效和/或选择性抑制作用。还揭示了利用这些化合物引发促醒、认知或注意力增强效应以及治疗物质使用障碍、注意缺陷（多动）障碍、抑郁障碍、双相障碍或其他神经精神障碍、睡眠障碍或认知障碍的方法。
• Potent and selective inhibitors of monoamine transporters; method of making; and use thereof
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services, Office of Technology Transfer, National Institutes of Health

  公开号：US10590074B2

  公开（公告）日：2020-03-17

  Disclosed herein are bisarylmethylthioacetamides and bisarylmethylthioethylamines useful as inhibitors of monoamine transporters. The compounds are potent and/or selective inhibitors of dopamine (DA), serotonin (5-HT), and/or norepinephrine (NE) reuptake via their respective transporters, DAT, SERT and NET. Also disclosed are methods for eliciting a wake-promoting or cognitive or attention enhancing effect and for treating substance use disorders, attention deficit (hyperactivity) disorder, depressive disorders, bipolar disorder or other neuropsychiatric disorders sleep disorders or cognitive impairment using the compounds.

  本文公开了可用作单胺转运体抑制剂的双芳基甲硫基乙酰胺和双芳基甲硫基乙胺。这些化合物是多巴胺（DA）、5-羟色胺（5-HT）和/或去甲肾上腺素（NE）通过各自的转运体 DAT、SERT 和 NET 再摄取的强效和/或选择性抑制剂。此外，还公开了利用这些化合物激发促进觉醒或认知或注意力增强效应以及治疗药物使用障碍、注意力缺陷（多动）症、抑郁症、双相情感障碍或其他神经精神疾病睡眠障碍或认知障碍的方法。
• Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors
  作者：Jianjing Cao、Rachel D. Slack、Oluyomi M. Bakare、Caitlin Burzynski、Rana Rais、Barbara S. Slusher、Theresa Kopajtic、Alessandro Bonifazi、Michael P. Ellenberger、Hideaki Yano、Yi He、Guo-Hua Bi、Zheng-Xiong Xi、Claus J. Loland、Amy Hauck Newman

  DOI：10.1021/acs.jmedchem.6b01373

  日期：2016.12.8

  The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in animal models of cocaine and methamphetamine abuse. Herein, we report a series of modafinil analogues that have an atypical DAT inhibitor profile. We extended SAR by chemically manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the phenyl rings, and/or functionalizing the terminal nitrogen with substituted piperazines, resulting in several novel leads such as 11b, which demonstrated high DAT affinity (K-i = 2.5 nM) and selectivity without producing concomitant locomotor stimulation in mice, as compared to cocaine. These results are consistent with an atypical DAT inhibitor profile and suggest that 11b may be a potential lead for development as a psychostimulant abuse medication.