5-chloro-3-methyl-2-(methylthio)benzothiazolium p-toluenesulfonate

• 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: 5-chloro-3-methyl-2-(methylthio)benzothiazolium p-toluenesulfonate
• 英文别名: 5-Chloro-2-methylthio-3-methylbenzothiazolium tosylate；5-chloro-3-methyl-2-methylsulfanyl-1,3-benzothiazol-3-ium;4-methylbenzenesulfonate
• 化学式: C₇H₇O₃S*C₉H₉ClNS₂
• 分子量: 401.959
• InChiKey: AQXSKUKYJFBTBT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  4.0
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-chloro-3-methyl-2-(methylthio)benzothiazolium p-toluenesulfonate 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  具有增强代谢稳定性的热休克蛋白 70 (Hsp70) 抑制剂可降低 tau 水平

  摘要：

  分子伴侣热休克蛋白 70 (Hsp70) 是一种新兴的神经退行性疾病药物靶点，因为它能够促进微管相关蛋白 tau (MAPT/tau) 的降解。最近，我们报道了 YM-08 作为脑渗透剂、变构 Hsp70 抑制剂，可降低 tau 水平。然而，YM-08 的苯并噻唑部分易受 CYP3A4 代谢的影响，限制了其作为化学探针的进一步应用。在这篇手稿中，我们通过将卤素原子系统地引入苯并噻唑环并改变末端吡啶中杂原子的位置，设计并合成了 17 种 YM-08 衍生物。在微粒体测定中，我们发现化合物 JG-23 的代谢稳定性提高了 12 倍，并且在两种基于细胞的模型中保留了降低 tau 水平的能力。

  DOI：

  10.1016/j.bmcl.2021.128025
• 作为产物：
  描述：

  2,5-二氯苯胺 在 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 5-chloro-3-methyl-2-(methylthio)benzothiazolium p-toluenesulfonate
  参考文献：
  名称：

  Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents

  摘要：

  The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogues designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 +/- 0.03 and 0.7 +/- 0.2 mu M, respectively). The analogues modestly destabilized the chaperone clients, Aka and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t(1/2) = 37 min) compared to MKT-077 (t(1/2) < 5 min). Finally, NMR titration experiments suggested that these analogues bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogues as chemical probes for studying Hsp70s roles in cancer.

  DOI：

  10.1021/ml400204n

文献信息

• Blue spectral sensitizers for non-tabular silver halide elements
  申请人：E. I. du Pont de Nemours and Company

  公开号：US05102781A1

  公开（公告）日：1992-04-07

  Zeromethine blue spectral sensitizing dyes have found utility in emulsions made without tabular grains. These emulsions are particularly useful for exposure to a light source rich in blue emission and are especially useful in radiographic elements designed for exposure to intensifying screens having such emission.

  零甲基蓝色光谱敏化染料在不使用平板晶粒制成的乳剂中发现了实用性。这些乳剂对于接受富含蓝色辐射的光源曝光特别有用，并且在设计用于接受具有此类辐射的增强屏幕曝光的放射成像元素中尤其有用。
• Biscyanines Linked by a 1,8-Naphthylene Skeleton: Models of Polymethine Dye Aggregates
  作者：Takashi Katoh、Keizo Ogawa、Yoshio Inagaki、Renji Okazaki

  DOI：10.1246/bcsj.70.2287

  日期：1997.9

  Biscyanines linked by a 1,8-naphthylene skeleton (1), suitable model compounds for a study on polymethine dye aggregates, were prepared. Biscyanines, 1b and 1c, having methoxy and chloro substituents on the benzothiazole nuclei, respectively, were identified to be in syn conformation based upon X-ray crystallographic analysis and NMR spectroscopy. Their absorption maxima were found to be hypsochromically shifted compared to those of the 1-naphthyl substituted monocyanines (2). Only a biscyanine 1e having negatively charged sulfonato groups on the benzothiazole nuclei showed a bathochromic shift and was found to exist as an anti conformer. These spectral shifts were reproduced by the calculations with the INDO/S-CI method and are in agreement with those based upon the molecular exciton theory. The positive shifts of the reduction potentials of 1 compared to those of 2 are explained by the Coulombic and orbital interactions between the two cyanine moieties.

  研究人员制备了由 1,8-萘骨架连接的双氰胺（1），它们是研究聚甲基染料聚集体的合适模型化合物。根据 X 射线晶体学分析和核磁共振光谱分析，苯并噻唑核上分别具有甲氧基和氯取代基的双氰胺 1b 和 1c 被确定为同步构象。与 1-萘基取代的单氰胺（2）相比，它们的吸收最大值发生了顺色转移。只有苯并噻唑核上带有带负电的磺酸基团的双氰胺 1e 出现了浴色偏移，并被发现以反构象形式存在。INDO/S-CI 方法的计算结果再现了这些光谱偏移，并与基于分子激子理论的计算结果一致。与 2 的还原电位相比，1 的还原电位发生了正偏移，这是因为两个氰基之间存在库仑和轨道相互作用。
• US5102781A
  申请人：——

  公开号：US5102781A

  公开（公告）日：1992-04-07
• US5656449A
  申请人：——

  公开号：US5656449A

  公开（公告）日：1997-08-12
• Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents
  作者：Xiaokai Li、Sharan R. Srinivasan、Jamie Connarn、Atta Ahmad、Zapporah T. Young、Adam M. Kabza、Erik. R. P. Zuiderweg、Duxin Sun、Jason E. Gestwicki

  DOI：10.1021/ml400204n

  日期：2013.11.14

  The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogues designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 +/- 0.03 and 0.7 +/- 0.2 mu M, respectively). The analogues modestly destabilized the chaperone clients, Aka and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t(1/2) = 37 min) compared to MKT-077 (t(1/2) < 5 min). Finally, NMR titration experiments suggested that these analogues bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogues as chemical probes for studying Hsp70s roles in cancer.