5-bromo-2-mercaptobenzonitrile | 1374518-00-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯硫酚类
• 英文名称: 5-bromo-2-mercaptobenzonitrile
• 英文别名: 5-Bromo-2-mercaptobenzonitrile；5-bromo-2-sulfanylbenzonitrile
• CAS: 1374518-00-9
• 化学式: C₇H₄BrNS
• 分子量: 214.085
• InChiKey: ASUIRNDOMTVKRI-UHFFFAOYSA-N

物化性质

• 沸点：
  301.0±27.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  24.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-2-mercaptobenzonitrile 在 ammonium hydroxide 、 sodium hypochlorite 、 sodium hydroxide 作用下， 反应 4.0h， 以51%的产率得到5-溴苯并[d]异噻唑-3-胺
  参考文献：
  名称：

  Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach

  摘要：

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.

  DOI：

  10.1021/jm5007929
• 作为产物：
  描述：

  2-氟-5-溴苯腈 在 sodium sulfide 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 以31.2%的产率得到5-bromo-2-mercaptobenzonitrile
  参考文献：
  名称：

  非布司他类似物作为黄嘌呤氧化还原酶抑制剂的计算机模拟研究：3D-QSAR 和分子对接联合研究

  摘要：

  摘要 我们探索了含有苯基取代的五元杂环的 107 种黄嘌呤氧化还原酶 (XOR) 抑制剂的分子对接和三维定量构效关系 (3D-QSAR) 模型。分子对接结果表明，Arg880、Phe914 和 Phe1009 可能是本研究中评估的 107 个 XOR 抑制剂靶向的潜在活性残基。拓扑异构体比较分子场分析 (CoMFA) (q2 = 0.571; r2 = 0.833) 用于 3D-QSAR。结果表明，苯被中等体积的取代基、氰基和带有羧基的五元杂环取代可能会增强异或抑制活性。基于这些结果设计了四种新化合物，每种化合物在体外都表现出潜在的 XOR 抑制活性。

  DOI：

  10.1016/j.molstruc.2019.01.017

文献信息

• Chemical synthesis, crystal structure, versatile evaluation of their biological activities and molecular simulations of novel pyrithiobac derivatives
  作者：Ren-Jun Wu、Kai-Xuan Zhou、Haijin Yang、Guo-Qing Song、Yong-Hong Li、Jia-Xin Fu、Xiao Zhang、Shu-Jing Yu、Li-Zhong Wang、Li-Xia Xiong、Cong-Wei Niu、Fu-Hang Song、Haitao Yang、Jian-Guo Wang

  DOI：10.1016/j.ejmech.2019.02.002

  日期：2019.4

  commercial herbicide with very low toxicity against mammals, it is worth exploring its derivatives for an extensive study. Herein, a total of 35 novel compounds were chemically synthesized and single crystal of 6–6 was obtained to confirm the molecular structure of this family of compounds. The novel PTB derivatives were fully evaluated against various biological platforms. From the bioassay results

  由于吡硫杆菌（PTB）是一种成功的商业除草剂，对哺乳动物的毒性极低，因此值得探索其衍生物以进行广泛研究。这里，总共有35种新型化合物化学合成和单晶6 - 6得到确认该化合物家族的分子结构。新型PTB衍生物已针对各种生物平台进行了全面评估。从生物测定结果来看，最好的AHAS抑制剂6-22表现出比PTB弱的除草活性，但更强的抗-念珠菌活性。对于植物病原真菌，6–26在50 mg / L剂量下显示出优异的活性。还观察到一些标题化合物的初步杀虫活性和抗病毒活性。令人惊讶的是，6-5对SARS-CoV M pro表现出有希望的抑制活性，IC 50为4.471μM，对哺乳动物293 T细胞的细胞毒性较低。基于分子建模的结果，HOMO-1被认为是影响AHAS抑制和的可能的结合模式的一个因素6 - 5与SARS-病毒M亲被预料到了。这是首次将PTB衍生物作为除草剂以外的生物制剂进行了研究。因此，本研究表明
• 一种硫取代苯基吡唑类XOR抑制剂及制备与应用
  申请人：华南理工大学

  公开号：CN108218777A

  公开（公告）日：2018-06-29

  本发明属于医药化工技术领域，公开了一种硫取代苯基吡唑类XOR抑制剂及制备与应用。所述硫取代苯基吡唑类XOR抑制剂具有式(I)所示的结构式。其制备方法为：将5‑溴‑2‑氟‑1‑氰基苯、硫化钠在DMF中室温反应，得到5‑溴‑2‑巯基‑1‑氰基苯，然后与溴代烷烃和无机碱在有机相中加热反应，得到5‑溴‑2‑烷硫基‑1‑氰基苯，再与1H‑吡唑‑4‑甲酸酯经C‑N偶联反应，水解、酸化后得到产物。本发明的产物对与痛风有关的黄嘌呤氧化酶表现出优良的抑制作用，并在急性高尿酸血症小鼠模型中，表现出优良的抑制效果，可用于制备抗高尿酸血症或痛风药物。
• About the reaction of aryl fluorides with sodium sulfide: investigation into the selectivity of substitution of fluorobenzonitriles to yield mercaptobenzonitriles via SNAr displacement of fluorine
  作者：Tony Taldone、Pallav D. Patel、Hardik J. Patel、Gabriela Chiosis

  DOI：10.1016/j.tetlet.2012.03.032

  日期：2012.5

  In this report we describe a simple synthesis of mercaptobenzonitriles from the reaction of fluorobenzonitriles with Na2S in DMF at room temperature and following direct treatment with Zn/HCl. Significantly, 2- and 4-fluorobenzonitriles substituted with chlorine or bromine, from the reaction of but not iodine, undergo selective substitution of fluorine at room temperature to yield synthetically useful halo-substituted mercaptobenzonitriles. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of Dual Death-Associated Protein Related Apoptosis Inducing Protein Kinase 1 and 2 Inhibitors by a Scaffold Hopping Approach
  作者：Ling-Jie Gao、Sona Kovackova、Michal Šála、Anna Teresa Ramadori、Steven De Jonghe、Piet Herdewijn

  DOI：10.1021/jm5007929

  日期：2014.9.25

  DRAK2 emerged as a promising drug target for the treatment of autoimmune diseases and to prevent graft rejection after organ transplantation. Screening of a compound library in a DRAK2 binding assay led to the identification of an isothiazolo[5,4-b]pyridine derivative as a novel ligand for DRAK2, displaying a K-d value of 1.6 mu M. Subsequent medicinal chemistry work led to the discovery of a thieno[2,3-b]pyridine derivative with strong DRAK2 binding affinity (K-d = 9 nM). Moreover, this compound also behaves as a functional inhibitor of DRAK2 enzymatic activity, displaying an IC50 value of 0.82 mu M, although lacking selectivity, when tested against DRAK1. This paper describes for the first time functionally active dual DRAK1 and DRAK2 inhibitors that can be used as starting point for the synthesis of chemical tool compounds to study DRAK1 and DRAK2 biology, or they can be considered as hit compounds for hit-to-lead optimization campaigns in drug discovery programs.
• In silico study of febuxostat analogs as inhibitors of xanthine oxidoreductase: A combined 3D-QSAR and molecular docking study
  作者：Xiaolei Li、Haiyan Zhou、Xianwei Mo、Lei Zhang、Jing Li

  DOI：10.1016/j.molstruc.2019.01.017

  日期：2019.4

  explored molecular docking and a three-dimensional quantitative structure-activity relationship (3D-QSAR) model of 107 xanthine oxidoreductase (XOR) inhibitors containing a phenyl-substituted five-membered heterocycle. Molecular-docking results showed that Arg880, Phe914, and Phe1009 might be potential active residues targeted by the 107 XOR inhibitors evaluated in this study. Topomer comparative molecular

  摘要 我们探索了含有苯基取代的五元杂环的 107 种黄嘌呤氧化还原酶 (XOR) 抑制剂的分子对接和三维定量构效关系 (3D-QSAR) 模型。分子对接结果表明，Arg880、Phe914 和 Phe1009 可能是本研究中评估的 107 个 XOR 抑制剂靶向的潜在活性残基。拓扑异构体比较分子场分析 (CoMFA) (q2 = 0.571; r2 = 0.833) 用于 3D-QSAR。结果表明，苯被中等体积的取代基、氰基和带有羧基的五元杂环取代可能会增强异或抑制活性。基于这些结果设计了四种新化合物，每种化合物在体外都表现出潜在的 XOR 抑制活性。