1-(3,4-dichlorophenyl)ethylideno-4-methylthiosemicarbazone

• 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: 1-(3,4-dichlorophenyl)ethylideno-4-methylthiosemicarbazone
• 英文别名: 1-[1-(3,4-Dichlorophenyl)ethylideneamino]-3-methylthiourea
• 化学式: C₁₀H₁₁Cl₂N₃S
• 分子量: 276.189
• InChiKey: DXRCBRDEXSOCGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,4-dichlorophenyl)ethylideno-4-methylthiosemicarbazone 、 2-溴丙酸乙酯 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 20.0h， 以75%的产率得到2-[1-(3,4-dichlorophenyl)ethylidenohydrazone]-3,5-dimethylthiazolidin-4-one
  参考文献：
  名称：

  Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi

  摘要：

  Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 810 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100 mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.048
• 作为产物：
  描述：

  4-甲基氨基硫脲 、 3,4-二氯苯乙酮 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以84%的产率得到1-(3,4-dichlorophenyl)ethylideno-4-methylthiosemicarbazone
  参考文献：
  名称：

  Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi

  摘要：

  Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 810 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100 mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.048

文献信息

• Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi
  作者：Gevanio Bezerra de Oliveira Filho、Marcos Veríssimo de Oliveira Cardoso、José Wanderlan Pontes Espíndola、Dayane Albuquerque Oliveira e Silva、Rafaela Salgado Ferreira、Pollyanne Lacerda Coelho、Pâmela Silva dos Anjos、Emanuelle de Souza Santos、Cássio Santana Meira、Diogo Rodrigo Magalhaes Moreira、Milena Botelho Pereira Soares、Ana Cristina Lima Leite

  DOI：10.1016/j.ejmech.2017.09.047

  日期：2017.12

  (Discrete Typing Units). Therefore, new drugs to treat this disease are necessary. Thiazole compounds have been described as potent trypanocidal agents. Here we report the structural planning, synthesis and anti-T. cruzi evaluation of a new series of 1,3-thiazoles (7–28), which were designed by placing this heterocycle instead of thiazolidin-4-one ring. The synthesis was conducted in an ultrasonic bath

  恰加斯病是美洲大陆最严重的健康问题之一。苯并硝唑（BDZ）和尼呋替莫（NFX）是唯一获准用于治疗的药物，除了在T. cruzi DTU（Discrete Typing Units）之间的易感性不同之外，在慢性阶段还表现出强烈的副作用和无效性。因此，治疗这种疾病的新药是必要的。噻唑化合物已被描述为有效的锥虫杀虫剂。在这里，我们报告了一系列新的1,3-噻唑类化合物的结构规划，合成和抗T. cruzi评估（7–28），这是通过放置该杂环而不是噻唑烷丁4一环来设计的。在室温下在超声浴中以2-丙醇为溶剂进行合成。通过改变连接在苯基和噻唑环上的取代基，观察到取代基保留，增强或大大提高了它们的抗克鲁维氏球菌活性。在一些情况下，在噻唑（化合物的5位甲基9，12和23）增加的杀锥虫属性。苯基交换为吡啶基杂环导致活性增加，从而产生最有效的抗锥虫病菌形式的化合物（14，IC 50trypo = 0.37μM）。
• Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi
  作者：Gevanio Bezerra de Oliveira Filho、Marcos Veríssimo de Oliveira Cardoso、José Wanderlan Pontes Espíndola、Luiz Felipe Gomes Rebello Ferreira、Carlos Alberto de Simone、Rafaela Salgado Ferreira、Pollyanne Lacerda Coelho、Cássio Santana Meira、Diogo Rodrigo Magalhaes Moreira、Milena Botelho Pereira Soares、Ana Cristina Lima Leite

  DOI：10.1016/j.bmc.2015.10.048

  日期：2015.12

  Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 810 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100 mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity. (C) 2015 Elsevier Ltd. All rights reserved.