1,4-diazabicyclo[2.2.2]octane (4-bromophenyl)carbamodithioate | 1414781-39-7

• 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-bromophenyl)carbamodithioate
• CAS: 1414781-39-7
• 化学式: C₆H₁₂N₂*C₇H₆BrNS₂
• 分子量: 360.342
• InChiKey: WAFDQBIJLONNCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 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-bromophenyl)carbamodithioate 在 三光气 、 potassium hydroxide 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 methyl 2-cyano-2-[3-(4-bromophenylphenyl)-4-oxo-1,3-thiazinan-2-ylidene]acetate
  参考文献：
  名称：

  Design, synthesis, and nematicidal activities of novel 1,3-thiazin(thiazol)-4-one derivatives against Meloidogyne incognita

  摘要：

  Four series of novel 1,3-thiazin(thiazol)-4-one derivatives were synthesized by Suzuki coupling. Preliminary bioassays showed that most of the synthesized compounds exhibited good inhibitory activity in vivo against root-knot nematodes, Meloidogyne spp. at 20 mg L−1. Among the tested compounds, we found that two compounds displayed 46.4% and 41.4% inhibitory activity even at 1 mg L−1, respectively.

  DOI：

  10.1177/1747519819857506
• 作为产物：
  描述：

  三乙烯二胺 、 二硫化碳 、 4-溴苯胺 以 丙酮 为溶剂， 反应 12.0h， 生成 1,4-diazabicyclo[2.2.2]octane (4-bromophenyl)carbamodithioate
  参考文献：
  名称：

  4-噻唑烷酮衍生物作为人二氢乳清酸酯脱氢酶的新型抑制剂的合成，构效关系和结合模式分析

  摘要：

  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。

  DOI：

  10.1039/c7md00081b

文献信息

• Facile and Versatile Synthesis of Alkyl and Aryl Isothiocyanates by Using Triphosgene and CoSolvent
  作者：Pengfei Liu、Chunyan Li、Jingwei Zhang、Xiaoyong Xu

  DOI：10.1080/00397911.2013.783600

  日期：2013.12.17

  efficient method for the conversion of alkyl and aryl amines to isothiocyanates via dithiocarbamates has been developed using (CH3)2CO-CS2 as co-solvent and triphosgene as dehydrosulfurization reagent. High yields, mild reaction conditions and excellent functional group compatibility make it become a versatile synthetic method for the preparation of isothiocyanates compared with reported methods. [Supplementary

  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
• Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase
  作者：Junsheng Zhu、Le Han、Yanyan Diao、Xiaoli Ren、Minghao Xu、Liuxin Xu、Shiliang Li、Qiang Li、Dong Dong、Jin Huang、Xiaofeng Liu、Zhenjiang Zhao、Rui Wang、Lili Zhu、Yufang Xu、Xuhong Qian、Honglin Li

  DOI：10.1021/jm501127s

  日期：2015.2.12

  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.
• Structural Optimization and Structure–Activity Relationships of <i>N</i>²-(4-(4-Methylpiperazin-1-yl)phenyl)-<i>N</i>⁸-phenyl-9<i>H</i>-purine-2,8-diamine Derivatives, a New Class of Reversible Kinase Inhibitors Targeting both EGFR-Activating and Resistance Mutations
  作者：Jiao Yang、Li-Jiao Wang、Jing-Jing Liu、Lei Zhong、Ren-Lin Zheng、Yong Xu、Pan Ji、Chun-Hui Zhang、Wen-Jing Wang、Xing-Dong Lin、Lin-Li Li、Yu-Quan Wei、Sheng-Yong Yang

  DOI：10.1021/jm301365e

  日期：2012.12.13

  This paper describe the structural optimization of a hit compound, N-2-(4-(4-methylpiperazin-1-yl)phenyl)-N-8-phenyl-9H-purine-2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclopentyl-N-2-(4-(4-methylpiperazin-1-yl)phenyl)-N-8-phenyl-9H-purine-2,8-diamine (9e) that exhibits significant in vitro antitumor potency against the non-small-cell lung cancer (NSCLC) cell lines HCC827 and H1975, which harbor EGFR-activating and drug-resistance mutations, respectively. Compound 9e was further assessed for potency and selectivity in enzymatic assays and in vivo anti-NSCLC studies. The results indicated that compound 9e is a highly potent kinase inhibitor against both EGFR-activating and resistance mutations and has good kinase spectrum selectivity across the kinome. In vivo, oral administration of compound 9e at a dose of 5 mg/kg caused rapid and complete tumor regression in a HCC827 xenograft model, and an oral dose of 50 mg/kg initiated a considerable antitumor effect in an H1975 xenograft model.