5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophene-2-carbaldehyde | 1313397-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophene-2-carbaldehyde
• 英文别名: 5-(1-oxo-3H-2-benzofuran-5-yl)thiophene-2-carbaldehyde
• CAS: 1313397-92-0
• 化学式: C₁₃H₈O₃S
• 分子量: 244.271
• InChiKey: CMIFYGDVYBWRMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophene-2-carbaldehyde 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 以74%的产率得到5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophene-2-carbaldehyde oxime
  参考文献：
  名称：

  L型氨基酸转运蛋白1（lat1）介导的穿孔素抑制剂的靶向递送。

  摘要：

  穿孔素是由细胞毒性效应细胞分泌的溶细胞性成孔糖蛋白。它是针对病毒感染和转化的细胞的免疫应答的关键组成部分，并已涉及许多人类疾病。小分子化合物可抑制穿孔素的活性，尽管对其作用部位的传递知之甚少。因此，在本研究中，研究了穿孔素抑制剂是否可以有效地和位点选择性地首先被递送到细胞毒性效应细胞中，其次被递送到其中储存了穿孔素的裂解颗粒中。这是通过设计和合成四种可以利用l型氨基酸转运蛋白（LAT1）的穿孔素抑制剂的前药来实现的，因为已知活化的免疫细胞会过表达LAT1。结果表明，通过使用LAT1的前药（进入人乳腺腺癌细胞（MCF-7））可以提高穿孔素抑制剂的细胞摄取。此外，这些前药还能够将穿孔素抑制剂递送至具有较低pH的细胞器（大鼠肝溶酶体）中。因此，通过使用这些前药，将来可以更彻底地研究穿孔素抑制活性的细胞内机制。此外，这种前药方法可以应用于其他药物，这些药物将从靶向递送到表达LAT1的细胞中受益，例

  DOI：

  10.1016/j.ijpharm.2015.12.034
• 作为产物：
  描述：

  2-(5-溴-2-噻吩基)-1,3-二氧戊环 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 水 、 sodium carbonate 作用下， 以 乙醇 、 丙酮 、 甲苯 为溶剂， 反应 5.0h， 生成 5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophene-2-carbaldehyde
  参考文献：
  名称：

  Inhibition of the pore-forming protein perforin by a series of aryl-substituted isobenzofuran-1(3H)-ones

  摘要：

  An aryl-substituted isobenzofuran-1(3H)-one lead compound was identified from a high throughput screen designed to find inhibitors of the lymphocyte pore-forming protein perforin. A series of analogs were then designed and prepared, exploring structure-activity relationships through variation of 2-thioxoimidazolidin-4-one and furan subunits on an isobenzofuranone core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 natural killer effector cells was determined. Several compounds showed excellent activity at concentrations that were non-toxic to the killer cells. This series represents a significant improvement on previous classes of compounds, being substantially more potent and largely retaining activity in the presence of serum. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.011

文献信息

• [EN] COMPOUNDS, PREPARATIONS AND USES THEREOF<br/>[FR] COMPOSÉS, LEURS PRÉPARATIONS ET LEURS UTILISATIONS
  申请人：PETER MACCALLUM CANCER INST

  公开号：WO2011075784A1

  公开（公告）日：2011-06-30

  The present invention provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.

  本发明提供了式（I）的新化合物，包括这些化合物的药物组合物以及使用这些化合物作为抑制穿孔素活性的药剂或药物，用于治疗患有与不良穿孔素活性相关的疾病或紊乱、或处于患有风险或易感染某种疾病或紊乱的受试者的方法。
• COMPOUNDS, PREPARATION AND USES THEREOF
  申请人：Spicer Julie Ann

  公开号：US20130065897A1

  公开（公告）日：2013-03-14

  The present invention provides novel compounds of the Formula I, pharmaceutical compositions comprising such compounds and methods for using such compounds as agents or drugs for inhibiting perforin activity and for treating a subject at risk of or susceptible to a disease or disorder, or having a disease or disorder associated with undesirable perforin activity.

  本发明提供了公式I的新化合物，包括这些化合物的制药组合物以及使用这些化合物作为抑制穿孔素活性的药剂或药物的方法，以及用于治疗处于风险或易感疾病或紊乱，或具有与不良穿孔素活性相关的疾病或紊乱的受试者。
• Inhibition of the pore-forming protein perforin by a series of aryl-substituted isobenzofuran-1(3H)-ones
  作者：Julie A. Spicer、Kristiina M. Huttunen、Christian K. Miller、William A. Denny、Annette Ciccone、Kylie A. Browne、Joseph A. Trapani

  DOI：10.1016/j.bmc.2011.12.011

  日期：2012.2

  An aryl-substituted isobenzofuran-1(3H)-one lead compound was identified from a high throughput screen designed to find inhibitors of the lymphocyte pore-forming protein perforin. A series of analogs were then designed and prepared, exploring structure-activity relationships through variation of 2-thioxoimidazolidin-4-one and furan subunits on an isobenzofuranone core. The ability of the resulting compounds to inhibit the lytic activity of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 natural killer effector cells was determined. Several compounds showed excellent activity at concentrations that were non-toxic to the killer cells. This series represents a significant improvement on previous classes of compounds, being substantially more potent and largely retaining activity in the presence of serum. (C) 2011 Elsevier Ltd. All rights reserved.
• l -Type amino acid transporter 1 (lat1)-mediated targeted delivery of perforin inhibitors
  作者：Kristiina M. Huttunen、Johanna Huttunen、Imke Aufderhaar、Mikko Gynther、William A. Denny、Julie A. Spicer

  DOI：10.1016/j.ijpharm.2015.12.034

  日期：2016.2

  adenocarcinoma cells (MCF-7)). Furthermore, these prodrugs were also able to deliver perforin inhibitors into the cell organelles having lower pH (rat liver lysosomes). Therefore, by using these prodrugs, intracellular mechanisms of perforin inhibitory activity can be studied more thoroughly in future. Moreover, this prodrug approach can be applied for other drugs that would benefit from targeted delivery

  穿孔素是由细胞毒性效应细胞分泌的溶细胞性成孔糖蛋白。它是针对病毒感染和转化的细胞的免疫应答的关键组成部分，并已涉及许多人类疾病。小分子化合物可抑制穿孔素的活性，尽管对其作用部位的传递知之甚少。因此，在本研究中，研究了穿孔素抑制剂是否可以有效地和位点选择性地首先被递送到细胞毒性效应细胞中，其次被递送到其中储存了穿孔素的裂解颗粒中。这是通过设计和合成四种可以利用l型氨基酸转运蛋白（LAT1）的穿孔素抑制剂的前药来实现的，因为已知活化的免疫细胞会过表达LAT1。结果表明，通过使用LAT1的前药（进入人乳腺腺癌细胞（MCF-7））可以提高穿孔素抑制剂的细胞摄取。此外，这些前药还能够将穿孔素抑制剂递送至具有较低pH的细胞器（大鼠肝溶酶体）中。因此，通过使用这些前药，将来可以更彻底地研究穿孔素抑制活性的细胞内机制。此外，这种前药方法可以应用于其他药物，这些药物将从靶向递送到表达LAT1的细胞中受益，例