1-bromo-4-isothiocyanato-2-(trifluoromethyl)benzene | 948294-47-1

• 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-bromo-4-isothiocyanato-2-(trifluoromethyl)benzene
• 英文别名: 3-trifluoromethyl-4-bromobenzene isothiocyanate；1-isothiocyanato-3-trifluoromethyl-4-bromobenzene；4-Bromo-3-trifluoromethylphenylisothiocyanate
• CAS: 948294-47-1
• 化学式: C₈H₃BrF₃NS
• 分子量: 282.084
• InChiKey: FUJRJHFGAPKJFK-UHFFFAOYSA-N

物化性质

• 沸点：
  285.4±40.0 °C(Predicted)
• 密度：
  1.63±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-bromo-4-isothiocyanato-2-(trifluoromethyl)benzene 在 ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(4-Bromo-3-(trifluoromethyl)phenyl)thiourea
  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：

  3-三氟甲基-4-溴苯胺 在 三乙烯二胺 、 三光气 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 16.0h， 生成 1-bromo-4-isothiocyanato-2-(trifluoromethyl)benzene
  参考文献：
  名称：

  Design, synthesis and biological evaluation of thiourea and nicotinamide-containing sorafenib analogs as antitumor agents

  摘要：

  硫脲和烟酰胺含量比索拉非尼更好的抗增殖和抗血管生成活性的类索拉非尼类似物已经被设计和合成。

  DOI：

  10.1039/c4md00536h

文献信息

• 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。
• Design and Discovery of Quinazoline- and Thiourea-Containing Sorafenib Analogs as EGFR and VEGFR-2 Dual TK Inhibitors
  作者：Shaofeng Sun、Jingwen Zhang、Ningning Wang、Xiangkai Kong、Fenghua Fu、Hongbo Wang、Jianwen Yao

  DOI：10.3390/molecules23010024

  日期：——

  MCF-7 and B16 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and TK kinases. Compounds 10b and 10q which exhibited the most potent inhibitory activities against EGFR (IC50 = 0.02 µM and 0.01 µM, respectively), VEGFR-2 (IC50 = 0.05 µM and 0.08 µM, respectively), and good antiproliferative activities, also displayed competitive anti-tumor activities

  EGFR和VEGFR-2在肿瘤生长，血管生成和转移中均起着关键作用，同时靶向EGFR和VEGFR-2代表了一种有前途的癌症治疗方法。在这项工作中，设计并合成了一系列新颖的含喹唑啉和硫脲的索拉非尼类似物（10a-v），作为EGFR和VEGFR-2双TK抑制剂。评估和描述了它们对EGFR和VEGFR-2的体外酶抑制活性，以及​​对HCT-116，MCF-7和B16细胞系的抗增殖活性。大多数化合物对细胞系和TK激酶均显示出有效的活性。化合物10b和10q对EGFR表现出最强的抑制活性（分别为IC50 = 0.02 µM和0.01 µM），VEGFR-2（分别为IC50 = 0.05 µM和0.08 µM），并且具有良好的抗增殖活性，
• Design, synthesis and biological evaluation of thiourea and nicotinamide-containing sorafenib analogs as antitumor agents
  作者：Xiangkai Kong、Zeyu Yao、Zuopeng He、Wenfang Xu、Jianwen Yao

  DOI：10.1039/c4md00536h

  日期：——

  Thiourea and nicotinamide-containing sorafenib analogs with better antiproliferative and anti-angiogenic activities than sorafenib were well designed and synthesized.

  硫脲和烟酰胺含量比索拉非尼更好的抗增殖和抗血管生成活性的类索拉非尼类似物已经被设计和合成。
• Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2
  作者：Shaofeng Sun、Zuopeng He、Mindong Huang、Ningning Wang、Zongzhong He、Xiangkai Kong、Jianwen Yao

  DOI：10.1016/j.bmc.2018.03.039

  日期：2018.5

  New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-Raf(V600E) and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-Raf(V600E) and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-Raf(V600E) with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay. (C) 2018 Elsevier Ltd. All rights reserved.
• 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.