4-chloro-5-methyl-1,2-dithiole-3-thione | 24045-84-9

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 4-chloro-5-methyl-1,2-dithiole-3-thione
• 英文别名: 4-chloro-5-methyl-[1,2]dithiole-3-thione；4-Chloro-5-methyldithiole-3-thione
• CAS: 24045-84-9
• 化学式: C₄H₃ClS₃
• 分子量: 182.719
• InChiKey: WISDMDNCRWWYNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  4-chloro-5-methyl-1,2-dithiole-3-thione 在 溶剂黄146 、 sodium nitrite 作用下， 以50%的产率得到C₈H₂Cl₂N₂O₂S₆
  参考文献：
  名称：

  Abazid, M.; Bertrand, H. O.; Christen, M. O., Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 88, # 1-4, p. 195 - 206

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氯乙酰乙酸乙酯 在 tetraphosphorus decasulfide 、 六甲基二硅氧烷 、 sulfur 作用下， 以12%的产率得到4-chloro-5-methyl-1,2-dithiole-3-thione
  参考文献：
  名称：

  1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)

  摘要：

  摘要 FabH 酶通过 II 型离解脂肪酸合成酶催化脂肪酸生物合成的第一步。这种重要酶的关键作用，加上其独特的结构特征和在细菌中的普遍存在，使其成为开发抗菌和抗寄生虫化合物的一个极具吸引力的新靶点。我们在美国国家癌症研究所数据库中搜索了与硫代内托霉素结构相似的化合物，硫代内托霉素是一种对 FabH 具有微弱活性的天然产物。通过搜索，我们发现了几种取代的 1,2-二硫代-3-酮类化合物，它们是来自以下两种细菌的 FabH 的强效抑制剂 大肠杆菌 (ecFabH) 和 金黄色葡萄球菌 (saFabH）的 FabH 的强效抑制剂。最有效的抑制剂是 4,5-二氯-1,2-二硫杂环戊烯-3-酮，其 50%的抑制浓度（IC 50 为 2 μM（ecFabH）和 0.16 μM（saFabH）。相应的 3-硫酮类似物表现出类似的活性。4-chloro 取代基被苯基取代的类似物也是有效的抑制剂，尽管效果稍差（IC 50 值分别为 5.7 μM 和 0.98 μM）。在没有底物的情况下，所有 5 氯化抑制剂与 FabH 预孵育时效果最好。移除过量的抑制剂后，酶-抑制剂复合物不会轻易恢复活性，这表明发生了缓慢的解离。与此形成鲜明对比的是，5-氯取代基被等位和等电子三氟甲基取代的一系列抑制剂的抑制效果较差（IC 50 值通常在 25 到 100 μM 之间），不需要预孵育期就能发挥最大活性，而且产生的酶-抑制剂复合物很容易解离。研究人员考虑了 5-氯-1,2-二硫杂环戊烯-3-酮和 5-氯-1,2-二硫杂环戊烯-3-硫酮与 FabH 结合的可能模式，其中考虑到了 5-氯取代基的作用。

  DOI：

  10.1128/aac.48.8.3093-3102.2004

文献信息

• 1,2-Dithiole-3-Ones as Potent Inhibitors of the Bacterial 3-Ketoacyl Acyl Carrier Protein Synthase III (FabH)
  作者：Xin He、Anne McElwee Reeve、Umesh R. Desai、Glen E. Kellogg、Kevin A. Reynolds

  DOI：10.1128/aac.48.8.3093-3102.2004

  日期：2004.8

  The enzyme FabH catalyzes the initial step of fatty acid biosynthesis via a type II dissociated fatty acid synthase. The pivotal role of this essential enzyme, combined with its unique structural features and ubiquitous occurrence in bacteria, has made it an attractive new target for the development of antibacterial and antiparasitic compounds. We have searched the National Cancer Institute database for compounds bearing structural similarities to thiolactomycin, a natural product which exhibits a weak activity against FabH. This search has yielded several substituted 1,2-dithiole-3-ones that are potent inhibitors of FabH from both Escherichia coli (ecFabH) and Staphylococcus aureus (saFabH). The most potent inhibitor was 4,5-dichloro-1,2-dithiole-3-one, which had 50% inhibitory concentration (IC ₅₀ ) values of 2 μM (ecFabH) and 0.16 μM (saFabH). The corresponding 3-thione analog exhibited comparable activities. Analogs in which the 4-chloro substituent was replaced with a phenyl group were also potent inhibitors, albeit somewhat less effectively (IC ₅₀ values of 5.7 and 0.98 μM for ecFabH and saFabH, respectively). All of the 5-chlorinated inhibitors were most effective when they were preincubated with FabH in the absence of substrates. The resulting enzyme-inhibitor complex did not readily regain activity after excess inhibitor was removed, suggesting that a slow dissociation occurs. In stark contrast, a series of inhibitors in which the 5-chloro substituent was replaced with the isosteric and isoelectronic trifluoromethyl group were poorer inhibitors (IC ₅₀ values typically ranging from 25 to >100 μM for both ecFabH and saFabH), did not require a preincubation period for maximal activity, and generated an enzyme-inhibitor complex which readily dissociated. Possible modes of binding of 5-chloro-1,2-dithiole-3-ones and 5-chloro-1,2-dithiole-3-thiones with FabH which account for the role of the 5-chloro substituent were considered.

  摘要 FabH 酶通过 II 型离解脂肪酸合成酶催化脂肪酸生物合成的第一步。这种重要酶的关键作用，加上其独特的结构特征和在细菌中的普遍存在，使其成为开发抗菌和抗寄生虫化合物的一个极具吸引力的新靶点。我们在美国国家癌症研究所数据库中搜索了与硫代内托霉素结构相似的化合物，硫代内托霉素是一种对 FabH 具有微弱活性的天然产物。通过搜索，我们发现了几种取代的 1,2-二硫代-3-酮类化合物，它们是来自以下两种细菌的 FabH 的强效抑制剂 大肠杆菌 (ecFabH) 和 金黄色葡萄球菌 (saFabH）的 FabH 的强效抑制剂。最有效的抑制剂是 4,5-二氯-1,2-二硫杂环戊烯-3-酮，其 50%的抑制浓度（IC 50 为 2 μM（ecFabH）和 0.16 μM（saFabH）。相应的 3-硫酮类似物表现出类似的活性。4-chloro 取代基被苯基取代的类似物也是有效的抑制剂，尽管效果稍差（IC 50 值分别为 5.7 μM 和 0.98 μM）。在没有底物的情况下，所有 5 氯化抑制剂与 FabH 预孵育时效果最好。移除过量的抑制剂后，酶-抑制剂复合物不会轻易恢复活性，这表明发生了缓慢的解离。与此形成鲜明对比的是，5-氯取代基被等位和等电子三氟甲基取代的一系列抑制剂的抑制效果较差（IC 50 值通常在 25 到 100 μM 之间），不需要预孵育期就能发挥最大活性，而且产生的酶-抑制剂复合物很容易解离。研究人员考虑了 5-氯-1,2-二硫杂环戊烯-3-酮和 5-氯-1,2-二硫杂环戊烯-3-硫酮与 FabH 结合的可能模式，其中考虑到了 5-氯取代基的作用。
• Synthesis and structure–activity relationships study of dithiolethiones as inducers of glutathione in the SH-SY5Y neuroblastoma cell line
  作者：Dennis A. Brown、Swati Betharia、Jui-Hung Yen、Quang Tran、Hitesh Mistry、Kari Smith

  DOI：10.1016/j.bmcl.2014.10.005

  日期：2014.12

  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.
• Abazid, M.; Bertrand, H. O.; Christen, M. O., Phosphorus, Sulfur and Silicon and the Related Elements, 1994, vol. 88, # 1-4, p. 195 - 206
  作者：Abazid, M.、Bertrand, H. O.、Christen, M. O.、Burgot, J. L.

  DOI：——

  日期：——