4-(benzo[d]thiazol-2-ylthio)-3-chloroaniline

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-(benzo[d]thiazol-2-ylthio)-3-chloroaniline
• 英文别名: 4-(1,3-benzothiazol-2-ylsulfanyl)-3-chloroaniline
• 化学式: C₁₃H₉ClN₂S₂
• mdl: MFCD00227023
• 分子量: 292.813
• InChiKey: DTSNLMOLTVGCGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(benzo[d]thiazol-2-ylthio)-3-chloroaniline 在 4-二甲氨基吡啶 、 三溴化硼 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 37.0h， 生成 N-(4-(benzo[d]thiazol-2-ylthio)phenyl)-3-bromo-2-hydroxybenzamide
  参考文献：
  名称：

  Hydroxybiphenylamide GroEL/ES Inhibitors Are Potent Antibacterials against Planktonic and Biofilm Forms of Staphylococcus aureus

  摘要：

  We recently reported the identification of a GroEL/ES inhibitor (1, N-(4-(benzo[d]thiazol-2-ylthio)-3-chlorophenyl)-3,5-dibromo-2-hydroxybenzamide) that exhibited in vitro antibacterial effects against Staphylococcus aureus comparable to vancomycin, an antibiotic of last resort. To follow up, we have synthesized 43 compound 1 analogs to determine the most effective functional groups of the scaffold for inhibiting GroEL/ES and killing bacteria. Our results identified that the benzothiazole and hydroxyl groups are important for inhibiting GroEL/ES-mediated folding functions, with the hydroxyl essential for antibacterial effects. Several analogs exhibited >50-fold selectivity indices between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. We found that MRSA was not able to easily generate acute resistance to lead inhibitors in a gain-of-resistance assay and that lead inhibitors were able to permeate through established S. aureus biofilms and maintain their bactericidal effects.

  DOI：

  10.1021/acs.jmedchem.8b01293
• 作为产物：
  描述：

  3,4-二氯硝基苯 在 盐酸 、 tin 、 potassium carbonate 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 4-(benzo[d]thiazol-2-ylthio)-3-chloroaniline
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS OF INHIBITING BACTERIAL CHAPERONIN SYSTEMS
  [FR] COMPOSÉS ET MÉTHODES D'INHIBITION DE SYSTÈMES DE CHAPERONINE BACTÉRIENNE

  摘要：

  本公开涉及新化合物和杀灭或抑制细菌生长的方法。在某些实施方式中，提供了一种杀灭或抑制细菌生长的方法。该方法包括向细菌施用式I的化合物或其药学上可接受的盐。在某些实施方式中，提供了一种杀灭或抑制细菌生长的方法。该方法包括向细菌施用驱虫药。

  公开号：

  WO2020092947A1

文献信息

• 巯基苯并噻唑脲类化合物、药物制剂及制备方法与应用
  申请人：绍兴市上虞区武汉理工大学高等研究院

  公开号：CN114524780A

  公开（公告）日：2022-05-24

  本发明公开了一种巯基苯并噻唑脲类化合物、药物制剂及制备方法与应用，该巯基苯并噻唑脲类化合物具有良好的抗金黄色葡萄球菌活性，在金黄色葡萄球菌感染的治疗中体现出良好的应用前景并体现了良好的应用潜力，并且制备工艺简单、操作方便。
• Surmounting the resistance against EGFR inhibitors through the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors
  作者：Sandra N. Milik、Amal Kamal Abdel-Aziz、Deena S. Lasheen、Rabah A.T. Serya、Saverio Minucci、Khaled A.M. Abouzid

  DOI：10.1016/j.ejmech.2018.06.011

  日期：2018.7

  In light of the emergence of resistance against the currently available EGFR inhibitors, our study focuses on tackling this problem through the development of dual EGFR/HER2 inhibitors with improved enzymatic affinities. Guided by the binding mode of the marketed dual EGFR/HER2 inhibitor, Lapatinib, we proposed the design of dual EGFR/HER2 inhibitors based on the 6-phenylthieno[2,3-d]pyrimidine as a core scaffold and hinge binder. After two cycles of screening aiming to identify the optimum aniline headgroup and solubilizing group, we eventually identified 27b as a dual EGFR/HER2 inhibitor with IC50 values of 91.7 nM and 1.2 mu M, respectively. Notably, 27b dramatically reduced the viability of various patient-derived cancer cells preferentially overexpressing EGFR/HER2 (A431, MDA-MBA-361 and SKBr3 with IC50 values of 1.45, 3.5 and 4.83 mu M, respectively). Additionally, 27b efficiently thwarted the proliferation of lapatinib-resistant human non-small lung carcinoma (NCI-H1975) cells, harboring T790 M mutation, with IC50 of 4.2 mu M. Consistently, 27b significantly blocked EGF-induced EGFR activation and inactivated its downstream AKT/mTOR/S6 signalling pathway triggering apoptotic cell death in NCI-H1975 cells. The present study presents a promising candidate for further design and development of novel EGFR/HER2 inhibitors capable of overcoming EGFR TKIs resistance. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors
  作者：Jacques Dumas、David Brittelli、Jinshan Chen、Brian Dixon、Holia Hatoum-Mokdad、Gerhard König、Robert Sibley、James Witowsky、Stephen Wong

  DOI：10.1016/s0960-894x(99)00433-3

  日期：1999.9

  Cathepsin D, a lysosomal aspartyl protease, has been implicated in the pathology of Alzheimer's disease as well as breast and ovarian cancer. A weakly active cathepsin D inhibitor was identified by high throughput screening. Subsequent optimization led to the discovery of a new class of small molecule inhibitors of this enzyme, culminating with the sulfonamide 13 (IC50 = 250 nM), (C) 1999 Elsevier Science Ltd. All rights reserved.
• Novel benzothiazole‒urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA
  作者：Liang Zha、Yunfeng Xie、Chengyao Wu、Ming Lei、Xueer Lu、Wenjian Tang、Jing Zhang

  DOI：10.1016/j.ejmech.2022.114333

  日期：2022.6
• INHIBITION OF BACTERIAL CHAPERONIN SYSTEMS
  申请人：THE TRUSTEES OF INDIANA UNIVERSITY

  公开号：US20210395210A1

  公开（公告）日：2021-12-23

  The present disclosure relates to novel compounds and methods of killing or inhibiting the growth of bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering a compound of formula I or a pharmaceutically acceptable salt thereof to bacteria. In some embodiments, a method of killing or inhibiting the growth of bacteria is provided. The method comprises administering an anthelmintic to bacteria.