2-[(4-methyl-2-nitrophenyl)thio]-N,N-dimethylbenzamide | 411208-40-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-[(4-methyl-2-nitrophenyl)thio]-N,N-dimethylbenzamide
• 英文别名: N,N-dimethyl-2-(4'-methyl-2'-nitrophenylthio)benzamide；N,N-dimethyl-2-(4-methyl-2-nitrophenylthio)benzamide；Benzamide, N,N-dimethyl-2-[(4-methyl-2-nitrophenyl)thio]-；N,N-dimethyl-2-(4-methyl-2-nitrophenyl)sulfanylbenzamide
• CAS: 411208-40-7
• 化学式: C₁₆H₁₆N₂O₃S
• 分子量: 316.381
• InChiKey: WTGPYYZJHQGVGG-UHFFFAOYSA-N

物化性质

• 熔点：
  105-106 °C
• 沸点：
  459.7±40.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(4-methyl-2-nitrophenyl)thio]-N,N-dimethylbenzamide 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 反应 16.0h， 以47%的产率得到N,N-dimethyl-2-(4'-bromoethyl-2'-nitrophenylthio)benzamide
  参考文献：
  名称：

  N，N-二甲基-2-（2'-氨基-4'-取代的苯硫基）苄胺的合成，体外表征和放射性标记：潜在的候选物质，作为选择性5-羟色胺转运体的配体。

  摘要：

  制备了一系列在4'-苯基位置取代的N，N-二甲基-2-（2'-氨基-4'-碘苯硫基）苄胺的N，N-二甲基化和N-单甲基化类似物，并进行了体外评估血清素转运蛋白（SERT）的选择性。制备了几种衍生物，其中4'-位未被取代的13和33a或被甲基14a和33b，乙烯基14b和34，乙基16和35，羟甲基20和41，羟乙基22，氟乙基23，羟丙基27和氟丙基取代28.使用[（3）H]西酞普兰，[（3）H] WIN 35,428或[（125）I] RTI在稳定表达转染的人类SERT，多巴胺转运蛋白（DAT）和去甲肾上腺素转运蛋白（NET）的细胞中竞争结合-55和[（3）H] nisoxetine分别显示出以下顺序的SERT亲和力（K（i）（nM））：14a（0.25）> 16（0.49）> 20（0.57）> 14b（1.12）> 13（1.59）> 33b（1.94）= 35（2.04）>> 23（8

  DOI：

  10.1021/jm050079o
• 作为产物：
  描述：

  4-溴-3-硝基甲苯 在 氯化亚砜 、 铜 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[(4-methyl-2-nitrophenyl)thio]-N,N-dimethylbenzamide
  参考文献：
  名称：

  Fluorinated Diaryl Sulfides as Serotonin Transporter Ligands:  Synthesis, Structure−Activity Relationship Study, and in Vivo Evaluation of Fluorine-18-Labeled Compounds as PET Imaging Agents

  摘要：

  A series of new, fluorine-containing substituted diphenyl sulfides was synthesized to serve as candidate ligands for positron emission tomography (PET) imaging of the serotonin transporter (SERT) and to further probe the structure-activity relationship (SAR) of this class of compounds. Candidate compounds were assayed for their affinities to the monoamine transporters (SERT, norepinephrine transporter (NET), and dopamine transporter (DAT)) in competitive binding experiments in vitro using cloned human transporters. From these in vitro assays, four compounds (7c-f) were chosen for further evaluation. All four compounds have nanomolar affinity for SERT (K-i 1.46 nM, 1.04 nM,1.83 nM, and 3.58 nM for 7c, 7d, 7e, and 7f, respectively). The F-18-labeled compounds, 16 and 18a-c, were prepared via a two-step radiosynthesis. Biodistribution studies in rats indicated that the F-18-labeled compounds localized in brain regions with high concentrations of SERT. Furthermore, competition experiments demonstrated that the binding of these radioligands in the rat brain was saturable, specific, and selective to SERT. Specific binding in the rat hypothalamus peaked at 5.6 for ligand 16 and 4.4 for 18b at 90 min after radioactivity administration. For ligand 18a, this same ratio was 8.4 at 120 min postinjection, while compound 18c displayed a lower-specific binding ratio of 2.4. In summary, four F-18-labeled ligands were prepared and evaluated as candidate PET imaging agents for SERT. Among these four ligands, three appear to be promising radioligands suitable for the labeling of SERT in vivo, with 18a providing a higher specific binding in vivo than 16 or 18b.

  DOI：

  10.1021/jm0400808

文献信息

• Synthesis and in vitro evaluation of novel derivatives of diphenylsulfide as serotonin transporter ligands
  作者：Johnny Vercouillie、Sylvie Mavel、Laurent Galineau、Tiziana Ragusa、Robert Innis、Michael Kassiou、Sylvie Chalon、Frédéric Dollé、Jean-Claude Besnard、Denis Guilloteau、Patrick Emond

  DOI：10.1016/j.bmcl.2005.11.066

  日期：2006.3

  radiopharmaceuticals to image the SERT by PET or SPECT would be very valuable in studying these diseases. For the development of imaging agents, we have synthesized novel derivatives of recently reported diphenylsulfide SERT ligands, in which the sulfur atom linking the two phenyl rings was replaced by an oxygen, sulfinyl, sulfonyl, amino or carbon group. Three of these exhibited good to high in vitro

  由于血清素转运蛋白（SERT）涉及多种神经退行性疾病和精神疾病，因此通过PET或SPECT对SERT成像的放射性药物在研究这些疾病中将非常有价值。为了开发显像剂，我们合成了最近报道的二苯硫醚SERT配体的新型衍生物，其中连接两个苯环的硫原子被氧，亚磺酰基，磺酰基，氨基或碳基团取代。其中三个表现出良好的体外亲和力（0.5 nM
• Substituted Diphenyl Sulfides as Selective Serotonin Transporter Ligands:  Synthesis and In Vitro Evaluation
  作者：Patrick Emond、Johnny Vercouillie、Robert Innis、Sylvie Chalon、Sylvie Mavel、Yves Frangin、Christer Halldin、Jean-Claude Besnard、Denis Guilloteau

  DOI：10.1021/jm010939a

  日期：2002.3.1

  influences the SERT affinity. (ii) Functions containing heteroatom at the 2'-position afford compounds with high SERT affinity. (iii) The nature of the substituent at the 4'-position slightly influences the SERT affinity whereas steric effect markedly decreases the SERT affinity. From this series, the most SERT selective derivatives (such as 8b, 8c, and 8g) are now evaluated for their potential as positron

  合成了一系列在1-，2'-和4'-位取代的二苯硫醚衍生物，并评估了它们在多巴胺，5-羟色胺（SERT）和去甲肾上腺素转运蛋白上的体外亲和力。对K（i）值的检查表明，这些衍生物大多数对SERT具有高亲和力和选择性。此外，在这些位置上的取代对SERT结合的影响不同：（i）在1位上连接的取代基的性质严重影响SERT亲和力。（ii）在2'-位含有杂原子的官能团提供具有高SERT亲和力的化合物。（iii）在4′-位的取代基的性质稍微影响了SERT亲和力，而空间效应显着降低了SERT亲和力。在该系列中，最精确的SERT选择性导数（例如8b，8c，
• Carbon-11 labelling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter
  作者：Jari Tarkiainen、Johnny Vercouillie、Patrick Emond、Johan Sandell、Jukka hiltunen、Yves Frangin、Denis Guilloteau、Christer Halldin

  DOI：10.1002/jlcr.523

  日期：2001.12

  Imaging by scintigraphy the serotonin transporter (5-HTT) in the living human brain would be of great value in research on the pathophysiology and treatment of neuropsychiatric disorders such as depression. For that reason, and in order to obtain a selective radiotracer applicable to PET, we report here the carbon-11 labelling of a selective 5-HTT radioligand: N, N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine or MADAM in two different positions: [p-11C-methyl]MADAM and [N-11C-methyl]MADAM. The synthesis of Bu3Sn-ADAM and N-dimethyl-MADAM is described. [p-11C-methyl]MADAM was obtained by a Stille coupling reaction between Bu3Sn-ADAM and [11C]methyl iodide using palladium (0) as a catalyst without (Ia) or with copper chloride as a co-catalyst (Ib). [N-11C-methyl]MADAM was obtained by an N-methylation reaction between N-demethyl-MADAM and [11C]methyl iodide (II). The carbon-11 incorporation yield in [p-11C-methyl]MADAM was 10–30% (Ia and Ib) and in [N-11C-methyl]MADAM was 75-80% (II). The final product in each case was obtained in 30 min total synthesis time, including HPLC purification and with >99% radiochemical purity. Copyright © 2001 John Wiley & Sons, Ltd.

  通过闪烁成像对活体人脑中的血清素转运体（5-HTT）进行成像，对于研究抑郁症等神经精神疾病的病理生理学和治疗具有重要价值。为此，为了获得一种适用于 PET 的选择性放射性示踪剂，我们在此报告一种选择性 5-HTT 放射性配体的碳-11 标记：N，N-二甲基-2-（2-氨基-4-甲基苯硫基）苄胺或 MADAM 在两个不同位置的碳-11 标记：[p-11C-甲基]MADAM 和 [N-11C- 甲基]MADAM。本文介绍了 Bu3Sn-ADAM 和 N-二甲基-MADAM 的合成。[p-11C-甲基]MADAM 是通过 Bu3Sn-ADAM 和[11C]甲基碘之间的 Stille 偶联反应得到的，该反应不使用钯 (0) 作为催化剂 (Ia)，也可以使用氯化铜作为辅助催化剂 (Ib)。[N-11C-methyl]MADAM 是通过 N-去甲基-MADAM 和 [11C]methyl iodide（II）的 N-甲基化反应得到的。p-11C-甲基]MADAM 的碳-11 结合率为 10-30%（Ia 和 Ib），而[N-11C-甲基]MADAM 的碳-11 结合率为 75-80%（II）。在每种情况下，最终产品的合成时间均为 30 分钟，包括 HPLC 纯化，放射化学纯度均大于 99%。Copyright © 2001 John Wiley & Sons, Ltd. All Rights Reserved.
• Carbon-11 and fluorine-18 labeled radioligands for positron emission tomography (PET) imaging for the brain serotonin transporters
  申请人：Huang Yiyun

  公开号：US20110097274A1

  公开（公告）日：2011-04-28

  This invention provides a compound having the structure: This invention also provides for related compounds and pharmaceutical compositions. This invention further provides for a compound that can be used for non-invasive method for positron emission tomography (PET) imaging of serotonin transporter sites in mammals comprising labeling serotonin transporter sites (SERT) with an image-generating amount of the radiolabeled compound disclosed herein and measuring spatial distribution of the compound in the mammal by PET so as to thereby image the serotonin transporter sites.

  这项发明提供了一种具有以下结构的化合物：此外，本发明还提供了相关的化合物和制药组合物。此外，本发明还提供了一种化合物，可用于非侵入性的正电子发射断层扫描（PET）成像方法，用于哺乳动物中的血清素转运体位点成像，包括使用本文所述的放射性标记化合物标记血清素转运体位点（SERT），并通过PET测量哺乳动物中化合物的空间分布，从而成像血清素转运体位点。
• Jarkas, Nachwa; McConathy, Jonathan; Ely, Timothy, Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S204 - S206
  作者：Jarkas, Nachwa、McConathy, Jonathan、Ely, Timothy、Kilts, Clinton D.、Votaw, John、Goodman, Mark M.

  DOI：——

  日期：——