1,4-diazabicyclo[2.2.2]octane (4-(trifluoromethyl)phenyl)carbamodithioate | 1430796-50-1

• 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: 1,4-diazabicyclo[2.2.2]octane (4-(trifluoromethyl)phenyl)carbamodithioate
• CAS: 1430796-50-1
• 化学式: C₆H₁₂N₂*C₈H₆F₃NS₂
• 分子量: 349.444
• InChiKey: JKKJNUOMOBXYRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  18.51
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1,4-diazabicyclo[2.2.2]octane (4-(trifluoromethyl)phenyl)carbamodithioate 在 ammonium hydroxide 、 三光气 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 4.0h， 生成 4-三氟甲基苯硫脲
  参考文献：
  名称：

  Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

  摘要：

  Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.

  DOI：

  10.1021/jm501127s
• 作为产物：
  描述：

  三乙烯二胺 、 二硫化碳 、 对三氟甲基苯胺 以 丙酮 为溶剂， 生成 1,4-diazabicyclo[2.2.2]octane (4-(trifluoromethyl)phenyl)carbamodithioate
  参考文献：
  名称：

  使用三光气和助溶剂简便而多功能地合成烷基和芳基异硫氰酸酯

  摘要：

  摘要 以(CH3)2CO-CS2 为共溶剂，三光气为脱氢硫化剂，开发了一种温和高效的二硫代氨基甲酸酯将烷基胺和芳基胺转化为异硫氰酸酯的方法。与报道的方法相比，高产率、温和的反应条件和优异的官能团兼容性使其成为制备异硫氰酸酯的通用合成方法。[本文提供补充材料。访问出版商的 Synthetic Communications® 在线版，获取以下免费补充资源：完整的实验和光谱细节。] 图形摘要

  DOI：

  10.1080/00397911.2013.783600

文献信息

• Synthesis, structure–activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase
  作者：Fanxun Zeng、Tiantian Qi、Chunyan Li、Tingfang Li、Honglin Li、Shiliang Li、Lili Zhu、Xiaoyong Xu

  DOI：10.1039/c7md00081b

  日期：——

  series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure–activity relationship was summarized. Further binding mode analysis revealed that compound 31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55,

  合成了一系列的4-噻唑烷酮衍生物，并作为新型人二氢乳清酸脱氢酶（h DHODH）抑制剂进行了评估。化合物26和31的IC 50值分别为1.75和1.12μM。构效关系进行了总结。进一步的结合模式分析表明，化合物31可以与Tyr38形成氢键，并与Ala55形成水介导的氢键，这对于维持该系列化合物的生物活性可能是必需的。R上苯基对位或间位的进一步结构优化将导致鉴定更有效的hDHODH抑制剂。
• Novel Selective and Potent Inhibitors of Malaria Parasite Dihydroorotate Dehydrogenase: Discovery and Optimization of Dihydrothiophenone Derivatives
  作者：Minghao Xu、Junsheng Zhu、Yanyan Diao、Hongchang Zhou、Xiaoli Ren、Deheng Sun、Jin Huang、Dongmei Han、Zhenjiang Zhao、Lili Zhu、Yufang Xu、Honglin Li

  DOI：10.1021/jm400938g

  日期：2013.10.24

  lack of effective antimalarial vaccines into consideration, it is of significant importance to develop novel antimalarial agents for the treatment of malaria. Herein, we elucidated the discovery and structure–activity relationships of a series of dihydrothiophenone derivatives as novel specific inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH). The most promising compound, 50,

  考虑到耐药性的出现和有效抗疟疾疫苗的缺乏，开发用于治疗疟疾的新型抗疟疾剂具有重要意义。在这里，我们阐明了一系列作为恶性疟原虫二氢乳清酸脱氢酶（Pf DHODH）的新型特异性抑制剂的二氢噻吩酮衍生物的发现及其与构效关系。最有前途的化合物50在体外选择性抑制Pf DHODH（IC 50 = 6 nM，相对于h DHODH具有1.4万倍以上的物种选择性）和体外寄生虫生长（IC 50分别针对3D7和Dd2细胞分别为15和18 nM）。此外，由体内药代动力学研究确定化合物50的口服生物利用度为40％。这些结果进一步表明，Pf DHODH是抗疟疾化学疗法的有效靶标，这项工作中报道的新型支架可能会导致发现新的抗疟疾药物。
• Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea against Meloidogyne incognita
  作者：Yaning Chang、Jingwei Zhang、Xiulei Chen、Zhong Li、Xiaoyong Xu

  DOI：10.1016/j.bmcl.2016.12.065

  日期：2017.6

  Two series of novel 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea were designed and synthesized. The bioassay results showed that most of the test compounds showed good nematicidal activity against M. incognita at the concentration of 10.0 mg L-1 in vivo. The compounds A13, A17 and B3 showed excellent nematicidal activity on the second stage juveniles of the root-knot nematode with the inhibition rate of 51.3%, 58.3% and 51.3% at the concentration of 1.0 mg L-1 respectively. It suggested that the structure of 1,2,3-benzotriazin-4-one derivatives containing thiourea and acylthiourea could be optimized further. (C) 2016 Elsevier Ltd. All rights reserved.