5-(4-chlorophenyl)-3H-1,2-dithiole-3-thione | 5761-16-0

• 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: 5-(4-chlorophenyl)-3H-1,2-dithiole-3-thione
• 英文别名: 3H-1,2-Dithiole-3-thione, 5-(4-chlorophenyl)-；5-(4-chlorophenyl)dithiole-3-thione
• CAS: 5761-16-0
• 化学式: C₉H₅ClS₃
• 分子量: 244.79
• InChiKey: PORXOKAPCYTNPQ-UHFFFAOYSA-N

物化性质

• 熔点：
  136 °C
• 沸点：
  388.2±52.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-3H-1,2-dithiole-3-thione 在 吡啶 作用下， 以 乙腈 、 苯 为溶剂， 反应 49.5h， 生成 bis<2,3-dichloro-(1-oxo<-5-(4-chlorophenyl)-1,2-dithiol-3-ylidene>-2-ethyl)-4-phenoxyacetic acid> disulfide
  参考文献：
  名称：

  Synthesis and in vitro anti-HIV evaluation of disulfide linked derivatives of 1,2-dithiol-3-ylidene ketones containing a 2,3-dichloro-4-phenoxy acetic acid moiety

  摘要：

  DOI：

  10.1016/0223-5234(92)90122-h
• 作为产物：
  描述：

  (4-氯苯甲酰基)乙酸乙酯 在 劳森试剂 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以71%的产率得到5-(4-chlorophenyl)-3H-1,2-dithiole-3-thione
  参考文献：
  名称：

  Synthesis and structure–activity relationships study of dithiolethiones as inducers of glutathione in the SH-SY5Y neuroblastoma cell line

  摘要：

  Parkinson's disease is a neurodegenerative disorder that involves the degeneration of nigrostriatal dopaminergic neurons. Elevated levels of reactive oxygen species have been shown to deplete cellular levels of the ubiquitous antioxidant glutathione, leading to oxidative stress and eventual neuronal cell death. Dithiolethiones, a class of sulfur-containing heterocyclic molecules, have been shown to induce cellular production of glutathione in a variety of tissues, but have not been extensively evaluated in neurons. Herein, we report the synthesis and preliminary structure-activity relationships study of several substituted dithiolethiones. Three molecules were identified (D3T, CPDT, and 2d) that potently induced cellular glutathione in the SH-SY5Y neuroblastoma cell line. Furthermore, these compounds were found to provide neuroprotection in the 6-hydroxydopamine model of neurotoxicity. This study suggests that dithiolethione-mediated neuroprotection may have potential as a disease-modifying antiparkinsonian therapy. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.005

文献信息

• Comparison of Various Aryl-Dithiolethiones and Aryl-Dithiolones As Hydrogen Sulfide Donors in the Presence of Rat Liver Microsomes
  作者：Madou-Marilyn Dali、Patrick M. Dansette、Daniel Mansuy、Jean-Luc Boucher

  DOI：10.1124/dmd.119.090274

  日期：2020.6

  H2S donor abilities of 18 dithiolethione and dithiolone analogs of ADT and ADO upon incubation with rat liver microsomes. It shows that, for all the studied compounds, maximal H2S formation was obtained after incubation with microsomes and NADPH and that this formation greatly decreased in the presence of N-benzylimidazole, a known inhibitor of cytochrome P450. This indicates that H2S formation from

  据报道，ADT (5-(p-甲氧基苯基)-3H-1,2-dithiole-3-thione, anetholedithiolethion, Sulfarlem) 和 ADO (5-(p-甲氧基苯基)-3H-1,2) 的微粒体代谢-dithiole-3-one, anetholedithiolone) 导致 H2S 的形成，主要来源于由细胞色素 P450 依赖性单加氧酶催化的氧化作用，并且在这些条件下，ADO 是比 ADT 更好的 供体。本文比较了 18 种二硫硫酮和 ADT 和 ADO 的二硫醇酮类似物与大鼠肝微粒体孵育后的 供体能力。它表明，对于所有研究的化合物，在与微粒体和 NADPH 孵育后获得了最大的 形成，并且这种形成在 N-苄基咪唑（一种已知的细胞色素 P450 抑制剂）存在下大大减少。这表明所有研究的化合物形成 需要，正如之前在 ADT 和 ADO
• Microwave assisted synthesis of functionalized 2H-chromene-2-thiones and 1,2-dithiole-3-thiones from β-oxodithioesters: Characterization, in vitro cytotoxicity and in silico docking studies
  作者：Siji Thonivalappil Bhaskaran、Paulson Mathew

  DOI：10.1016/j.molstruc.2021.132071

  日期：2022.3

  β-Oxodithiocarboxylates condensed with salicylaldehydes in the presence of triethylamine under microwave irradiation to afford 2H-chromene-2-thiones in excellent yields. Microwave heating of a mixture of β-oxodithioesters and Lawesson's reagent (LR) under solvent-free conditions led to sulfurization of the β-oxodithioesters and subsequent cyclization to form 1,2-dithiole-3-thiones. The products were

  β-氧代二硫代羧酸盐在三乙胺存在下在微波辐射下与水杨醛缩合，以优异的产率得到 2 H-色烯-2-硫酮。在无溶剂条件下对 β-氧代二硫酯和劳森试剂 (LR) 的混合物进行微波加热，导致 β-氧代二硫酯硫化，随后环化形成 1,2-二硫醇-3-硫酮。产物通过NMR光谱和X-射线衍射技术表征。与之前的报道不同，这些反应在没有任何金属催化剂的情况下，在无溶剂条件下的短时间内发生。体内细胞毒性和计算机对接研究揭示了这些化合物作为抗癌剂的实用性。
• Neue 1,2-Dithiol-3-thion-S-oxid-Verbindungen enthaltende Arzneimittel
  申请人：Kali-Chemie Pharma GmbH

  公开号：EP0343303A1

  公开（公告）日：1989-11-29

  Es werden die Verwendung von gegebenenfalls im Phenylring substituierten 5-Phenyl-3H-1,2-dithiol-3-thion-S-oxiden als Wirkstoffe in hepatoprotektiven Arzneimitteln und neue im Phenylring substituierte 5-Phenyl-3H-1,2-dithiol-3-thion-S-oxide beschrieben.

  介绍了作为保肝药物活性成分的 5-苯基-3H-1,2-二硫醇-3-硫酮-S-氧化物（可选择在苯基环上取代）和在苯基环上取代的新型 5-苯基-3H-1,2-二硫醇-3-硫酮-S-氧化物的用途。
• Neue 1,2-dithiol-3-thion-S-oxid-Verbindungen enthaltende Arzneimittel
  申请人：Kali-Chemie Pharma GmbH

  公开号：EP0343573A1

  公开（公告）日：1989-11-29

  Es werden die Verwendung von gegebenenfalls im Phenylring substituierten 5-Phenyl-3H-1,2-dithiol-3-thion-S-oxiden als Wirkstoffe in hepatoprotektiven Arzneimitteln und neue im Phenylring substituierte 5-Phenyl-3H-1,2-dithiol-­3-thion-S-oxide beschrieben.

  介绍了作为保肝药物活性成分的 5-苯基-3H-1,2-二硫醇-3-硫酮-S-氧化物（可选择在苯基环上取代）和在苯基环上取代的新型 5-苯基-3H-1,2-二硫醇-3-硫酮-S-氧化物的用途。
• Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
  作者：Zi-Long Song、Feifei Bai、Baoxin Zhang、Jianguo Fang

  DOI：10.1021/acs.jafc.9b06360

  日期：2020.2.19

  Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine- or H2O2 -induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.