4,6-difluoro-1,3-benzothiazole-2(3H)-thione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 4,6-difluoro-1,3-benzothiazole-2(3H)-thione
• 英文别名: 4,6-difluoro-3H-1,3-benzothiazole-2-thione
• 化学式: C₇H₃F₂NS₂
• 分子量: 203.236
• InChiKey: MENJHULQACIILM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-difluoro-1,3-benzothiazole-2(3H)-thione 在 ammonium hydroxide 、 sodium hypochlorite 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.75h， 生成
  参考文献：
  名称：

  Water Networks Contribute to Enthalpy/Entropy Compensation in Protein–Ligand Binding

  摘要：

  The mechanism (or mechanisms) of enthalpy-entropy (HIS) compensation in protein ligand binding remains controversial, and there are still no predictive models (theoretical or experimental) in which hypotheses of ligand binding can be readily tested. Here we describe a particularly well-defined system of protein and ligands-human carbonic anhydrase (HCA) and a series of benzothiazole sulfonamide ligands with different patterns of fluorination-that we use to define enthalpy/entropy (HIS) compensation in this system thermodynamically and structurally. The binding affinities of these ligands (with the exception of one ligand, in which the deviation is understood) to HCA are, despite differences in fluorination pattern, indistinguishable; they nonetheless reflect significant and compensating changes in enthalpy and entropy of binding. Analysis reveals that differences in the structure and thermodynamic properties of the waters surrounding the bound ligands are an important contributor to the observed H/S compensation. These results support the hypothesis that the molecules of water filling the active site of a protein, and surrounding the ligand, are as important as the contact interactions between the protein and the ligand for biomolecular recognition, and in determining the thermodynamics of binding.

  DOI：

  10.1021/ja4075776
• 作为产物：
  描述：

  二硫化碳 、 2-溴-4,6-二氟苯胺 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以80%的产率得到4,6-difluoro-1,3-benzothiazole-2(3H)-thione
  参考文献：
  名称：

  一种方便的无金属方法，由邻卤代苯胺和二硫化碳合成苯并噻唑硫酮

  摘要：

  已经开发了一种方便的方法来制备各种1,3-苯并噻唑-2（3 H）-硫酮。反应是在80-140℃下，在1,8-二氮杂双环[5.4.0]十一碳-7-烯存在下，由邻卤代苯胺衍生物和二硫化碳进行的，得到相应的1,3-苯并噻唑-2（3 H）-硫酮衍生物，收率良好。 环化-杂环-苯并噻唑-胺-二硫化碳-串联反应

  DOI：

  10.1055/s-0031-1289713

文献信息

• Ortho-Selective Nucleophilic Aromatic Substitution Reactions of Polyhaloanilines with Potassium/Sodium <i>O</i>-Ethyl Xanthate:  A Convenient Access to Halogenated 2(3<i>H</i>)-Benzothiazolethiones
  作者：Lei Zhu、Mingbao Zhang

  DOI：10.1021/jo049056s

  日期：2004.10.1

  Polyhaloanilines bearing an ortho halogen atom undergo smooth nucleophilic aromatic substitution reactions with anionic sulfur nucleophiles at relatively mild temperatures (95−120 °C). These reactions are very efficient and highly ortho-selective. With potassium/sodium O-ethyl xanthate as a nucleophile, subsequent cyclization follows to afford halogenated 2(3H)-benzothiazolethiones (2-mercaptobenzothiazoles)

  带有邻卤原子的聚卤苯胺在相对温和的温度下（95-120°C）与阴离子硫亲核试剂进行平滑的亲核芳族取代反应。这些反应非常有效且具有高邻位选择性。以O-乙基黄原酸钾/钠为亲核试剂，随后的环化反应以高收率提供卤代的2（3 H）-苯并噻唑硫酮（2-巯基苯并噻唑）。
• Discovery of Benzothiazolylpyrazole-4-Carboxamides as Potent Succinate Dehydrogenase Inhibitors through Active Fragment Exchange and Link Approach
  作者：Yan-Ming Yin、Zong-Yue Sun、Da-Wei Wang、Zhen Xi

  DOI：10.1021/acs.jafc.3c03646

  日期：2023.10.11

  Succinate dehydrogenase (SDH) is an attractive target for developing green fungicides to manage agricultural pathogens in modern agriculture research. Herein, in this work, we report the discovery of benzothiazolylpyrazole-4-carboxamides I-III as potent SDH inhibitors using active fragment exchange and link approach. The results of the fungicidal activity assays showed that some of the synthesized

  琥珀酸脱氢酶（SDH）是现代农业研究中开发绿色杀菌剂来管理农业病原体的一个有吸引力的目标。在这项工作中，我们报告了使用活性片段交换和连接方法发现苯并噻唑基吡唑-4-甲酰胺I - III作为有效的 SDH 抑制剂。杀菌活性测定结果表明，一些合成的化合物对受试真菌表现出优异的抑制作用。系统的构效关系研究发现了化合物Ip , N -(1-((4,6-二氟苯并[ d ]噻唑-2-基)硫基)丙-2-基)-3-(二氟甲基)- N -甲氧基-1-甲基-1 H -吡唑-4-甲酰胺，对禾谷镰刀菌 ( Fusarium graminearum Schw) 的杀菌活性 (EC 50 = 0.93 μg/mL) 比商业杀菌剂 thifluzamide (EC 50 > 50 μg/mL) 更高，啶酰菌胺 (EC 50 > 50 μg/mL)。分子模拟研究表明疏水相互作用是配体和SDH 之间的主要驱动力。令人欣喜的
• 10.1021/acs.jafc.4c01739
  作者：Yin, Yan-Ming、Zhang, Xiao-Ming、Shang, Xiao-Yue、Gao, Zi-Han、Liang, Zheng-Bei、Wang, Da-Wei、Xi, Zhen

  DOI：10.1021/acs.jafc.4c01739

  日期：——

  Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized

  琥珀酸脱氢酶（SDH）被认为是发现杀菌剂的理想靶点。为了开发新型 SDH 抑制剂，在这项工作中，使用活性片段交换和连接方法设计并合成了 31 种新型苯并噻唑-2-基硫代苯基吡唑-4-甲酰胺，作为有前景的 SDH 抑制剂。抗真菌活性测试结果表明，大多数合成的化合物对测试的真菌表现出显着的抑制作用。化合物Ig N- (2-(((5-氯苯并[ d ]噻唑-2-基)硫代)甲基)苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺，具有EC对四种真菌的 50 值低于 10 μg/mL，对花生尾孢菌的50值甚至低于 2 μg/mL，显示出比商业杀菌剂 thifluzamide 更优异的抗真菌活性，特别是化合物Ig和Im 的预防效力高达 90.6%对立枯丝核菌的抑制效果分别为 81.3% 和 81.3%，与阳性杀菌剂 thifluzamide 相似。分子模拟研究表明疏水相互作用是配体和SDH之间的
• Synthesis of 2-Mercaptobenzothiazoles via DBU-Promoted Tandem Reaction of <i>o</i>-Haloanilines and Carbon Disulfide
  作者：Fei Wang、Shangjun Cai、Zhipeng Wang、Chanjuan Xi

  DOI：10.1021/ol2011105

  日期：2011.6.17

  An efficient strategy for the synthesis of a variety of 2-mercaptobenzothiazole derivatives has been developed. The reaction proceeded from o-haloaniline derivatives and carbon disulfide via a tandem reaction in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford the corresponding 2-mercaptobenzothiazole derivatives in good to excellent yields.
• Novel KCNQ2/Q3 Agonists as Potential Therapeutics for Epilepsy and Neuropathic Pain
  作者：Paul C. Fritch、Grant McNaughton-Smith、George S. Amato、James F. Burns、C. Wesley Eargle、Rosemarie Roeloffs、William Harrison、Leslie Jones、Alan D. Wickenden

  DOI：10.1021/jm901497b

  日期：2010.1.28

  Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GABAergic activity and thus a number of associated side effects. Modulation of the M-current through opening of KCNQ channels has been proposed as a way to attenuate neuroexcitability and have a therapeutic benefit for the treatment Of seizure disorders. Therefore, as part Of our program to identify new treatments for epilepsy, we set out to identify agonists of KCNQ channels. High throughput screening of our corporate collection led to the identification of 1, adamantane-1-carboxylic acid (3-methyl-3H-benzothiazol-2-ylidine) hydrazide, a potent KCNQ2/Q3 agonist. Herein, we describe the syntheses and structure-activity relationships of analogues of I its well as their in vivo activity in animal models of epilepsy and neuropathic pain.