3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carbaldehyde | 1313398-86-5

• 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: 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carbaldehyde
• 英文别名: 3-(1-oxo-3H-2-benzofuran-5-yl)-1,2-thiazole-4-carbaldehyde
• CAS: 1313398-86-5
• 化学式: C₁₂H₇NO₃S
• 分子量: 245.258
• InChiKey: HQTBSZQWEGPKDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：
  84.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-硫代乙内酰脲 、 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carbaldehyde 在 溶剂黄146 、 β-丙氨酸 作用下， 反应 15.0h， 以86%的产率得到(E,Z)-5-((3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazol-4-yl)methylene)-2-thioxoimidazolidin-4-one
  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
• 作为产物：
  描述：

  艾司西酞普兰杂质 在 sodium tetrahydroborate 、 pyridinium chlorochromate on silica gel 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 邻二氯苯 为溶剂， 反应 43.08h， 生成 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-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

• 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.