5,6-dimethoxybenzo[b]thiophen-3(2H)-one | 95735-64-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5,6-dimethoxybenzo[b]thiophen-3(2H)-one
• 英文别名: 5,6-dimethoxy-1-benzothiophen-3-one
• CAS: 95735-64-1
• 化学式: C₁₀H₁₀O₃S
• 分子量: 210.254
• InChiKey: MEDPGNDUIOQOLP-UHFFFAOYSA-N

物化性质

• 沸点：
  378.9±42.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-dimethoxybenzo[b]thiophen-3(2H)-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到5,6-dimethoxy-1,1-dioxo-1-benzothiophen-3-one
  参考文献：
  名称：

  Discovery of the first known small-molecule inhibitors of heme-regulated eukaryotic initiation factor 2α (HRI) kinase

  摘要：

  A series of indeno[1,2-c]pyrazoles were discovered to be the first known inhibitors of heme-regulated eukaryotic initiation factor 2 alpha (HRI) kinase. The synthesis, structure-activity relationship profile, and in-vitro pharmacological characterization of this inaugural series of HRI kinase inhibitors are detailed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.033
• 作为产物：
  描述：

  邻苯二甲醚 在 盐酸 、 氯化亚砜 、 草酰氯 、 potassium carbonate 、 sodium hydroxide 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 16.0h， 生成 5,6-dimethoxybenzo[b]thiophen-3(2H)-one
  参考文献：
  名称：

  Novel inhibitors of AChE and Aβ aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer's disease

  摘要：

  DOI：

  10.1016/j.ejmech.2022.114305

文献信息

• Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**
  作者：Alexander Sailer、Joyce C. M. Meiring、Constanze Heise、Linda N. Pettersson、Anna Akhmanova、Julia Thorn‐Seshold、Oliver Thorn‐Seshold

  DOI：10.1002/anie.202104794

  日期：2021.10.25

  first cellular application of the emerging near-quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubs allow simultaneous visible-light imaging and photoswitching in live cells, delivering cell-precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death

  我们通过合理设计细胞骨架蛋白微管蛋白的光药物PHTub抑制剂，报告了新兴的近定量光开关吡咯半硫靛蓝的首次细胞应用。PHTub允许在活细胞中同时进行可见光成像和光开关，提供微管动力学的细胞精确光调制，以及对细胞周期进程和细胞死亡的光控制。这是首次将半硫靛蓝光药物用于活细胞的高时空分辨率生物控制。它还通过启用暗活性设计来克服细胞光图案化过程中残留的背景活性，展示了近定量光开关的实用性。这项工作为使用PHTub进行高精度微管研究开辟了新视野，并展示了吡咯半硫靛蓝作为一系列其他生物靶标的光控制的有价值支架的细胞适用性。
• Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo
  作者：Alexander Sailer、Franziska Ermer、Yvonne Kraus、Rebekkah Bingham、Ferdinand H Lutter、Julia Ahlfeld、Oliver Thorn-Seshold

  DOI：10.3762/bjoc.16.14

  日期：——

  Background: Hemithioindigo is a promising molecular photoswitch that has only recently been applied as a photoswitchable pharmacophore for control over bioactivity in cellulo. Uniquely, in contrast to other photoswitches that have been applied to biology, the pseudosymmetric hemithioindigo scaffold has allowed the creation of both dark-active and lit-active photopharmaceuticals for the same binding site by a priori design. However, the potency of previous hemithioindigo photopharmaceuticals has not been optimal for their translation to other biological models.

  Results: Inspired by the structure of tubulin-inhibiting indanones, we created hemithioindigo-based indanone-like tubulin inhibitors (HITubs) and optimised their cellular potency as antimitotic photopharmaceuticals. These HITubs feature reliable and robust visible-light photoswitching and high fatigue resistance. The use of the hemithioindigo scaffold also permitted us to employ a para-hydroxyhemistilbene motif, a structural feature which is denied to most azobenzenes due to the negligibly short lifetimes of their metastable Z-isomers, which proved crucial to enhancing the potency and photoswitchability. The HITubs were ten times more potent than previously reported hemithioindigo photopharmaceutical antimitotics in a series of cell-free and cellular assays, and allowed robust photocontrol over tubulin polymerisation, microtubule (MT) network structure, cell cycle, and cell survival.

  Conclusions: HITubs represent a powerful addition to the growing toolbox of photopharmaceutical reagents for MT cytoskeleton research. Additionally, as the hemithioindigo scaffold allows photoswitchable bioactivity for substituent patterns inaccessible to the majority of current photopharmaceuticals, wider adoption of the hemithioindigo scaffold may significantly expand the scope of cellular and in vivo targets addressable by photopharmacology.

  背景：Hemithioindigo是一种有前途的分子光开关，最近才被应用作为细胞内生物活性控制的可光开关药效基团。与已应用于生物学的其他光开关相比，伪对称的Hemithioindigo骨架独特地通过先验设计允许在同一结合位点上创建暗活性和亮活性的光药物。然而，先前的Hemithioindigo光药物的效力对于它们在其他生物模型中的转化并不理想。 结果：受到抑制微管的吲哚酮结构的启发，我们创建了基于Hemithioindigo的类似吲哚酮的微管抑制剂（HITubs），并优化了它们作为抗有丝分裂光药物的细胞效力。这些HITubs具有可靠和强大的可见光光开关性能和高疲劳抗性。Hemithioindigo骨架的使用还使我们能够采用一个对大多数偶氮苯来说是被拒绝的para-羟基半亚苄基团，这对于增强效力和光开关性至关重要。在一系列无细胞和细胞实验中，HITubs比先前报道的Hemithioindigo光药物抗有丝分裂活性物质更有效，可以可靠地控制微管聚合、微管网络结构、细胞周期和细胞存活。 结论：HITubs是对微管细胞骨架研究不断增长的光药物试剂工具箱的强大补充。此外，由于Hemithioindigo骨架允许对大多数当前光药物无法访问的取代模式进行光开关生物活性，广泛采用Hemithioindigo骨架可能显著扩大细胞和体内靶标的范围，从而扩展光药理学的适用范围。
• Hemithioindigos for Cellular Photopharmacology: Desymmetrised Molecular Switch Scaffolds Enabling Design Control over the Isomer‐Dependency of Potent Antimitotic Bioactivity
  作者：Alexander Sailer、Franziska Ermer、Yvonne Kraus、Ferdinand H. Lutter、Carsten Donau、Maximilian Bremerich、Julia Ahlfeld、Oliver Thorn‐Seshold

  DOI：10.1002/cbic.201800752

  日期：2019.5.15

  for adapted experimental tools, but rather protein binding site sterics, that typically force whether the trans (dark) or cis (lit) isomer is the more bioactive. We now present the rational design of HOTubs, the first hemithioindigo-based pharmacophores enabling photoswitchable control over endogenous biological activity in cellulo. HOTubs optically control microtubule depolymerisation and cell death

  具有光开关生物活性的类药物小分子-光药物-允许生物学家对基因操作无法访问的关键生物系统进行精确，可逆，时空精确控制的研究。所公开的光敏药效基团几乎完全是偶氮苯，这限制了光药理学的结构和取代基范围。更不利的是，对于偶氮苯试剂而言，不是研究人员对适应性实验工具的需求，而是蛋白质结合位点的空间位阻，通常迫使反式（深色）或顺式（亮）异构体具有更高的生物活性。现在，我们介​​绍HOTubs的合理设计，HOTubs是首个基于半硫靛蓝的药效基团，能够对纤维素中的内源性生物活性进行光控控制。HOTubs光学控制未修饰的哺乳动物细胞中的微管解聚和细胞死亡。值得注意的是，我们显示了半硫靛蓝的不对称性如何允许对Z-或E-（深色或浅色）毒性的有丝分裂剂进行先验设计，而相应的偶氮苯只具有浅色毒性。因此，我们证明了半硫靛蓝能够实现取代基的重要扩展，并为生物系统提供了光药理学干预措施的设计范围。
• 一类砜及亚砜类化合物、其制备方法及医药用途
  申请人：中国药科大学

  公开号：CN114591312B

  公开（公告）日：2023-07-28

  本发明涉及一类砜及亚砜类化合物、其制备方法及医药用途，该类化合物具有乙酰胆碱酯酶抑制能力以及对痴呆症状具有治疗活性，本发明还公开了含有所述化合物的药用组合物，以及所述化合物或其药用盐或含有其的组合物在制备治疗阿尔茨海默病及相关痴呆症状的药物中的应用。
• Tinh, Nguyen Huu; Cayuela, R.; Destrade, C., Molecular Crystals and Liquid Crystals (1969-1991), 1985, vol. 122, p. 141 - 150
  作者：Tinh, Nguyen Huu、Cayuela, R.、Destrade, C.、Malthete, J.

  DOI：——

  日期：——