N-(3-amino-3-oxopropyl)-2-hydroxy-4-(5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophen-2-yl)benzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(3-amino-3-oxopropyl)-2-hydroxy-4-(5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophen-2-yl)benzamide
• 英文别名: N-(3-amino-3-oxopropyl)-2-hydroxy-4-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]benzamide
• 化学式: C₂₂H₁₈N₂O₅S
• 分子量: 422.461
• InChiKey: IODUOEDGFDXYHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-羟基-4-碘苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium fluoride 、 硫酸 、 sodium carbonate 、 1-羟基苯并三唑 、 silver nitrate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 6.0h， 生成 N-(3-amino-3-oxopropyl)-2-hydroxy-4-(5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)thiophen-2-yl)benzamide
  参考文献：
  名称：

  Diarylthiophenes as inhibitors of the pore-forming protein perforin

  摘要：

  Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of substituted-benzene and -pyridyl moieties as bioisosteres for 2-thioxoimidazolidin-4-one (A) on a thiophene (B) -isobenzofuranone (C) scaffold. The resulting compounds were tested for their ability to inhibit perforin lytic activity in vitro. Carboxamide (23) shows a 4-fold increase over (2) in lytic activity against isolated perforin and provides good rationale for continued development within this class. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.

  DOI：

  10.1016/j.bmcl.2015.12.003

文献信息

• Diarylthiophenes as inhibitors of the pore-forming protein perforin
  作者：Christian K. Miller、Kristiina M. Huttunen、William A. Denny、Jagdish K. Jaiswal、Annette Ciccone、Kylie A. Browne、Joseph A. Trapani、Julie A. Spicer

  DOI：10.1016/j.bmcl.2015.12.003

  日期：2016.1

  Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of substituted-benzene and -pyridyl moieties as bioisosteres for 2-thioxoimidazolidin-4-one (A) on a thiophene (B) -isobenzofuranone (C) scaffold. The resulting compounds were tested for their ability to inhibit perforin lytic activity in vitro. Carboxamide (23) shows a 4-fold increase over (2) in lytic activity against isolated perforin and provides good rationale for continued development within this class. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.