N-(4-chlorophenyl)-5-(5-methyl-1H-imidazol-4-yl)-1,3,4-thiadiazol-2-amine

• 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: N-(4-chlorophenyl)-5-(5-methyl-1H-imidazol-4-yl)-1,3,4-thiadiazol-2-amine
• 化学式: C₁₂H₁₀ClN₅S
• 分子量: 291.764
• InChiKey: YSJYEKPSRUECMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  94.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-3-[(5-methyl-1H-imidazole-4-carbonyl)amino]thiourea 在 硫酸 作用下， 反应 2.0h， 生成 N-(4-chlorophenyl)-5-(5-methyl-1H-imidazol-4-yl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii

  摘要：

  由食物和水源的寄生虫弓形虫（T. gondii）引起的先天性和获得性弓形虫病是全球最普遍的人兽共患病之一。T. gondii是一种有限的细胞内寄生虫，因此，成功、高效和强大的宿主细胞入侵过程对其生存、增殖和传播至关重要。在本研究中，我们筛选了一系列在C5位置带有咪唑环的新型1,3,4-噻二唑-2-卤代苯胺（1b-12b）对T. gondii宿主细胞入侵和增殖的影响。为了实现这一目标，这些化合物首先在体外进行细胞毒性试验，评估它们对人类成纤维细胞的细胞毒性，然后评估其抗寄生虫效力。结果显示，所有这些化合物在T. gondii生长抑制（IC50）和对寄生虫的选择性指数（SI）方面都比对照药物磺胺二甲嘧啶和替米考星表现更好。随后，具有间氟2b、间氯5b、间溴8b、间碘11b和对碘12b取代的最有效化合物进行了测试，以抑制滴虫的入侵和随后的增殖。所有化合物均通过对滴虫和寄生囊形成的直接作用显著抑制了寄生虫的入侵和细胞内增殖。其中最有效的是对碘衍生物12b，与未经处理的宿主细胞相比，它使感染宿主细胞的百分比减少了44％，每个囊泡中滴虫的数量减少了93％。总的来说，这些研究表明1,3,4-噻二唑1b-12b，特别是IC50为4.70 µg/mL，SI为20.89的12b，可以被认为是未来设计和合成有效且选择性地阻止T. gondii进入宿主细胞的抗弓形虫药物的早期药物。

  DOI：

  10.3390/cells10051053

文献信息

• Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles
  作者：André P. Liesen、Thiago M. de Aquino、Cristiane S. Carvalho、Vânia T. Lima、Janete M. de Araújo、José G. de Lima、Antônio R. de Faria、Edésio J.T. de Melo、Antonio J. Alves、Elias W. Alves、Anselmo Q. Alves、Alexandre J.S. Góes

  DOI：10.1016/j.ejmech.2010.05.017

  日期：2010.9

  In this work we reported the synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities in vitro of three new compound series obtained from ethyl(5-methyl-1-H-imidazole-4-carboxylate): acylthiosemicarbazide analogues 3a-d, 4-thiazolidinone analogues 4a-d and 1,3,4-thiadiazole analogues 5a-d. All synthesized compounds were characterized by IR, H-1, C-13 NMR and HRMS. The majority of the tested compounds show excellent anti-T gondii activity when compared to hydroxyurea and sulfadiazine. In addition it was also shown that most of the compounds in this study have a better performance against intracellular tachyzoites. The results for antimicrobial activity evaluation showed weak antibacterial and antifungal activities for all the tested molecules, when compared with the standard drugs (chloramphenicol and rifampicin for antibacterial activity; nistatin and ketoconazole for antifungal activity). (C) 2010 Elsevier Masson SAS. All rights reserved.
• 1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii
  作者：Lidia Węglińska、Adrian Bekier、Katarzyna Dzitko、Barbara Pacholczyk-Sienicka、Łukasz Albrecht、Tomasz Plech、Piotr Paneth、Agata Paneth

  DOI：10.3390/cells10051053

  日期：——

  Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b–12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b–12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells.

  由食物和水源的寄生虫弓形虫（T. gondii）引起的先天性和获得性弓形虫病是全球最普遍的人兽共患病之一。T. gondii是一种有限的细胞内寄生虫，因此，成功、高效和强大的宿主细胞入侵过程对其生存、增殖和传播至关重要。在本研究中，我们筛选了一系列在C5位置带有咪唑环的新型1,3,4-噻二唑-2-卤代苯胺（1b-12b）对T. gondii宿主细胞入侵和增殖的影响。为了实现这一目标，这些化合物首先在体外进行细胞毒性试验，评估它们对人类成纤维细胞的细胞毒性，然后评估其抗寄生虫效力。结果显示，所有这些化合物在T. gondii生长抑制（IC50）和对寄生虫的选择性指数（SI）方面都比对照药物磺胺二甲嘧啶和替米考星表现更好。随后，具有间氟2b、间氯5b、间溴8b、间碘11b和对碘12b取代的最有效化合物进行了测试，以抑制滴虫的入侵和随后的增殖。所有化合物均通过对滴虫和寄生囊形成的直接作用显著抑制了寄生虫的入侵和细胞内增殖。其中最有效的是对碘衍生物12b，与未经处理的宿主细胞相比，它使感染宿主细胞的百分比减少了44％，每个囊泡中滴虫的数量减少了93％。总的来说，这些研究表明1,3,4-噻二唑1b-12b，特别是IC50为4.70 µg/mL，SI为20.89的12b，可以被认为是未来设计和合成有效且选择性地阻止T. gondii进入宿主细胞的抗弓形虫药物的早期药物。