3-(2-isothiocyanatoethyl)-5-methoxy-1H-indole | 60114-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(2-isothiocyanatoethyl)-5-methoxy-1H-indole
• CAS: 60114-18-3
• 化学式: C₁₂H₁₂N₂OS
• 分子量: 232.306
• InChiKey: NXNJINJDHJRFFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-isothiocyanatoethyl)-5-methoxy-1H-indole 在 hydrazine hydrate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以72%的产率得到N-(2-(5-methoxy-1H-indol-3-yl)ethyl)hydrazinecarbothioamide
  参考文献：
  名称：

  含有吲哚片段作为有效和选择性抗癌剂的新型硫半脲类衍生物。

  摘要：

  高效，安全的抗癌药物的研发仍在促进人类健康。在本报告中，设计并合成了一系列新型的含吲哚片段的硫半碳环素衍生物。大多数化合物对PC3，MGC803和EC109细胞系均表现出优异的抗增殖活性，且IC50（0.14-12μM）低。特别地，化合物5j可以选择性地抑制三个测试的肿瘤细胞中的PC3细胞，IC50值为0.14μM，这可能归因于将吲哚片段引入TSC结构后的协同作用。同时，与3-AP和DPC相比，化合物5j在PC3细胞中对两种正常的WPMY-1和GES-1细胞系表现出更高的选择性。我们还发现5j可以有效抑制PC3细胞增殖，定植并诱导细胞凋亡。更重要的是，5j可能通过阻止EMT过程来显着抑制迁移和侵袭，但对细胞周期没有影响。总体而言，我们的研究结果表明，具有吲哚硫半脲的结构的5j可以用作进一步优化和开发的有用的抗癌药物。

  DOI：

  10.1016/j.ejmech.2019.111764
• 作为产物：
  描述：

  5-甲氧基色胺 、 N,N'-硫羰基二咪唑 以 四氢呋喃 为溶剂， 反应 3.17h， 以90%的产率得到3-(2-isothiocyanatoethyl)-5-methoxy-1H-indole
  参考文献：
  名称：

  Melatonin-sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug-prodrug’ mechanism of action

  摘要：

  Background and PurposeNeurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties.Experimental ApproachCompound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug–prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia.Key ResultsITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration‐dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2–antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re‐oxygenation from stress by increasing the expression of haem oxygenase‐1 and reducing free radical production.Conclusion and ImplicationsITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases.

  DOI：

  10.1111/bph.13025

文献信息

• Design, Synthesis, and Melatoninergic Activity of New Azido- and Isothiocyanato-Substituted Indoles
  作者：Andrew Tsotinis、Pandelis A. Afroudakis、Kathryn Davidson、Anjali Prashar、David Sugden

  DOI：10.1021/jm7010723

  日期：2007.12.13

  To develop irreversibly binding ligands for the melatonin receptor(s) as tools for tracing the primary melatonin binding site, we report on the design and synthesis of new melatoninergic azido- and isothiocyanato-substituted indoles. All active compounds were partial agonists or antagonists in the Xenopus melanophore assay, the most potent being the 5-OMe C3-substituted azido 45 and isothiocyanato 46 analogues.
• [EN] USE OF 3-(2-ISOTHIOCYANATOETHYL)-5-METHOXY-1H-INDOLE FOR THE TREATMENT OF DEGENERATIVE RETINAL DISEASES<br/>[ES] USO DEL 3-(2-ISOTIOCIANATOETIL)-5-METOXI-1H-INDOL PARA EL TRATAMIENTO DE LAS ENFERMEDADES DEGENERATIVAS DE LA RETINA<br/>[FR] UTILISATION DU 3-(2-ISOTHIOCYANATOÉTHYL)-5-MÉTHOXY-1H-INDOLE POUR LE TRAITEMENT DES MALADIES DÉGÉNÉRATIVES DE LA RÉTINE
  申请人：UNIV DALACANT / UNIV DE ALICANTE 70%

  公开号：WO2020012052A1

  公开（公告）日：2020-01-16

  La presente invención se refiere a un compuesto de fórmula (I), o una de sus sales farmacéuticamente aceptables, para uso en el tratamiento preventivo o terapéutico de las enfermedades degenerativas retinianas. (I)
• Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent
  作者：Zhangxu He、Hui Qiao、Feifei Yang、Wenjuan Zhou、Yunpeng Gong、Xinhui Zhang、Haojie Wang、Bing Zhao、Liying Ma、Hong-min Liu、Wen Zhao

  DOI：10.1016/j.ejmech.2019.111764

  日期：2019.12

  are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC50 (0.14-12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC50 value of

  高效，安全的抗癌药物的研发仍在促进人类健康。在本报告中，设计并合成了一系列新型的含吲哚片段的硫半碳环素衍生物。大多数化合物对PC3，MGC803和EC109细胞系均表现出优异的抗增殖活性，且IC50（0.14-12μM）低。特别地，化合物5j可以选择性地抑制三个测试的肿瘤细胞中的PC3细胞，IC50值为0.14μM，这可能归因于将吲哚片段引入TSC结构后的协同作用。同时，与3-AP和DPC相比，化合物5j在PC3细胞中对两种正常的WPMY-1和GES-1细胞系表现出更高的选择性。我们还发现5j可以有效抑制PC3细胞增殖，定植并诱导细胞凋亡。更重要的是，5j可能通过阻止EMT过程来显着抑制迁移和侵袭，但对细胞周期没有影响。总体而言，我们的研究结果表明，具有吲哚硫半脲的结构的5j可以用作进一步优化和开发的有用的抗癌药物。
• Melatonin-sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug-prodrug’ mechanism of action
  作者：Javier Egea、Izaskun Buendia、Esther Parada、Elisa Navarro、Patricia Rada、Antonio Cuadrado、Manuela G López、Antonio G García、Rafael León

  DOI：10.1111/bph.13025

  日期：2015.4

  Background and PurposeNeurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties.Experimental ApproachCompound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug–prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia.Key ResultsITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration‐dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2–antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re‐oxygenation from stress by increasing the expression of haem oxygenase‐1 and reducing free radical production.Conclusion and ImplicationsITH12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases.