摩熵化学
数据库官网
小程序
打开微信扫一扫
首页 分子通 化学资讯 化学百科 反应查询 关于我们
请输入关键词

1-(2-((bis(4-fluorophenyl)-methyl)thio)ethyl)piperazine

中文名称
——
中文别名
——
英文名称
1-(2-((bis(4-fluorophenyl)-methyl)thio)ethyl)piperazine
英文别名
1-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)piperazine;1-(2-((Bis(4-fluorophenyl)methyl)thio)ethyl)piperazine;1-[2-[bis(4-fluorophenyl)methylsulfanyl]ethyl]piperazine
1-(2-((bis(4-fluorophenyl)-methyl)thio)ethyl)piperazine化学式
CAS
——
化学式
C19H22F2N2S
mdl
——
分子量
348.46
InChiKey
JIRSEFCXFJDFAN-UHFFFAOYSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    3.6
  • 重原子数:
    24
  • 可旋转键数:
    6
  • 环数:
    3.0
  • sp3杂化的碳原子比例:
    0.37
  • 拓扑面积:
    40.6
  • 氢给体数:
    1
  • 氢受体数:
    5

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为反应物:
    描述:
    1-(2-((bis(4-fluorophenyl)-methyl)thio)ethyl)piperazine双氧水 作用下, 以 甲醇溶剂黄146异丙醇 为溶剂, 生成 1-(4-(2-((bis(4-fluorophenyl)methyl)sulfinyl)ethyl)piperazin-1-yl)-3-phenylpropan-2-ol
    参考文献:
    名称:
    Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors
    摘要:
    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.
    DOI:
    10.1021/acs.jmedchem.6b01373
  • 作为产物:
    参考文献:
    名称:
    Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors
    摘要:
    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.
    DOI:
    10.1021/acs.jmedchem.6b01373
点击查看最新优质反应信息

文献信息

  • Structure–Activity Relationships for a Series of (Bis(4-fluorophenyl)methyl)sulfinyl Alkyl Alicyclic Amines at the Dopamine Transporter: Functionalizing the Terminal Nitrogen Affects Affinity, Selectivity, and Metabolic Stability
    作者:Rachel D. Slack、Therese C. Ku、Jianjing Cao、JoLynn B. Giancola、Alessandro Bonifazi、Claus J. Loland、Alexandra Gadiano、Jenny Lam、Rana Rais、Barbara S. Slusher、Mark Coggiano、Gianluigi Tanda、Amy Hauck Newman
    DOI:10.1021/acs.jmedchem.9b01188
    日期:2020.3.12
    diastereomeric separation, as well as improvements in potency and pharmacokinetics were desirable for discovering pipeline drug candidates. Thus, a series of bis(4-fluorophenyl)methyl)sulfinyl)alkyl alicyclic amines, where the piperazine-2-propanol scaffold was modified, were designed, synthesized, and evaluated for binding affinities at DAT, as well as the serotonin transporter and σ1 receptors. Within
    非典型多巴胺转运蛋白 (DAT) 抑制剂已在精神兴奋剂滥用的临床前模型中显示出治疗潜力。在大鼠中,1-(4-(2-((双(4-氟苯基)甲基)亚磺酰基)乙基)-哌嗪-1-基)-丙-2-醇 ( 3b ) 可有效降低两者的增强作用可卡因和甲基苯丙胺,但本身没有表现出精神兴奋行为。虽然3b的进一步开发正在进行中,但非对映异构体分离以及效力和药代动力学的改进对于发现管道候选药物是可取的。因此,设计、合成了一系列双(4-氟苯基)甲基)亚磺酰基)烷基脂环胺,其中对哌嗪-2-丙醇支架进行了修饰,并评估了其在 DAT 的结合亲和力,以及血清素转运蛋白和σ1个受体。在该系列中,14a显示出比3b ( K i = 230 nM)更高的 DAT 亲和力 ( K i = 23 nM) 、人肝微粒体中的中等代谢稳定性和 hERG/DAT 亲和力比 = 28。而14a相对于运动活性增加对于载体,它明显低于可卡因产生的活
  • 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。
  • US9862679B2
    申请人:——
    公开号:US9862679B2
    公开(公告)日:2018-01-09
  • [EN] POTENT AND SELECTIVE INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF<br/>[FR] INHIBITEURS PUISSANTS ET SÉLECTIFS DE TRANSPORTEURS DE MONOAMINE; PROCÉDÉ DE FABRICATION; ET LEUR UTILISATION
    申请人:US HEALTH
    公开号:WO2014138518A2
    公开(公告)日:2014-09-12
    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.
查看更多

同类化合物

(βS)-β-氨基-4-(4-羟基苯氧基)-3,5-二碘苯甲丙醇 (S)-(-)-7'-〔4(S)-(苄基)恶唑-2-基]-7-二(3,5-二-叔丁基苯基)膦基-2,2',3,3'-四氢-1,1-螺二氢茚 (S)-盐酸沙丁胺醇 (S)-3-(叔丁基)-4-(2,6-二甲氧基苯基)-2,3-二氢苯并[d][1,3]氧磷杂环戊二烯 (S)-2,2'-双[双(3,5-三氟甲基苯基)膦基]-4,4',6,6'-四甲氧基联苯 (S)-1-[3,5-双(三氟甲基)苯基]-3-[1-(二甲基氨基)-3-甲基丁烷-2-基]硫脲 (R)富马酸托特罗定 (R)-(-)-盐酸尼古地平 (R)-(+)-7-双(3,5-二叔丁基苯基)膦基7''-[((6-甲基吡啶-2-基甲基)氨基]-2,2'',3,3''-四氢-1,1''-螺双茚满 (R)-3-(叔丁基)-4-(2,6-二苯氧基苯基)-2,3-二氢苯并[d][1,3]氧杂磷杂环戊烯 (R)-2-[((二苯基膦基)甲基]吡咯烷 (N-(4-甲氧基苯基)-N-甲基-3-(1-哌啶基)丙-2-烯酰胺) (5-溴-2-羟基苯基)-4-氯苯甲酮 (5-溴-2-氯苯基)(4-羟基苯基)甲酮 (5-氧代-3-苯基-2,5-二氢-1,2,3,4-oxatriazol-3-鎓) (4S,5R)-4-甲基-5-苯基-1,2,3-氧代噻唑烷-2,2-二氧化物-3-羧酸叔丁酯 (4-溴苯基)-[2-氟-4-[6-[甲基(丙-2-烯基)氨基]己氧基]苯基]甲酮 (4-丁氧基苯甲基)三苯基溴化磷 (3aR,8aR)-(-)-4,4,8,8-四(3,5-二甲基苯基)四氢-2,2-二甲基-6-苯基-1,3-二氧戊环[4,5-e]二恶唑磷 (2Z)-3-[[(4-氯苯基)氨基]-2-氰基丙烯酸乙酯 (2S,3S,5S)-5-(叔丁氧基甲酰氨基)-2-(N-5-噻唑基-甲氧羰基)氨基-1,6-二苯基-3-羟基己烷 (2S,2''S,3S,3''S)-3,3''-二叔丁基-4,4''-双(2,6-二甲氧基苯基)-2,2'',3,3''-四氢-2,2''-联苯并[d][1,3]氧杂磷杂戊环 (2S)-(-)-2-{[[[[3,5-双(氟代甲基)苯基]氨基]硫代甲基]氨基}-N-(二苯基甲基)-N,3,3-三甲基丁酰胺 (2S)-2-[[[[[[((1R,2R)-2-氨基环己基]氨基]硫代甲基]氨基]-N-(二苯甲基)-N,3,3-三甲基丁酰胺 (2-硝基苯基)磷酸三酰胺 (2,6-二氯苯基)乙酰氯 (2,3-二甲氧基-5-甲基苯基)硼酸 (1S,2S,3S,5S)-5-叠氮基-3-(苯基甲氧基)-2-[(苯基甲氧基)甲基]环戊醇 (1-(4-氟苯基)环丙基)甲胺盐酸盐 (1-(3-溴苯基)环丁基)甲胺盐酸盐 (1-(2-氯苯基)环丁基)甲胺盐酸盐 (1-(2-氟苯基)环丙基)甲胺盐酸盐 (-)-去甲基西布曲明 龙胆酸钠 龙胆酸叔丁酯 龙胆酸 龙胆紫 龙胆紫 齐达帕胺 齐诺康唑 齐洛呋胺 齐墩果-12-烯[2,3-c][1,2,5]恶二唑-28-酸苯甲酯 齐培丙醇 齐咪苯 齐仑太尔 黑染料 黄酮,5-氨基-6-羟基-(5CI) 黄酮,6-氨基-3-羟基-(6CI) 黄蜡,合成物 黄草灵钾盐