N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
• 英文别名: N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]pyridin-3-yl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide
• 化学式: C₂₆H₂₁N₃O₅S₂
• 分子量: 519.602
• InChiKey: CNGZPZNJXOICKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以58%的产率得到N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide sodium salt
  参考文献：
  名称：

  Substituted arylsulphonamides as inhibitors of perforin-mediated lysis

  摘要：

  The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.048
• 作为产物：
  描述：

  2,3-二氢-1,4-苯并二氧-6-磺酰氯 、 5-(5-(5-aminopyridin-3-yl)thiophen-2-yl)-2-methylisoindolin-1-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到N-(5-(5-(2-methyl-1-oxoisoindolin-5-yl)thiophen-2-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
  参考文献：
  名称：

  Substituted arylsulphonamides as inhibitors of perforin-mediated lysis

  摘要：

  The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.048

文献信息

• Substituted arylsulphonamides as inhibitors of perforin-mediated lysis
  作者：Julie A. Spicer、Christian K. Miller、Patrick D. O'Connor、Jiney Jose、Kristiina M. Huttunen、Jagdish K. Jaiswal、William A. Denny、Hedieh Akhlaghi、Kylie A. Browne、Joseph A. Trapani

  DOI：10.1016/j.ejmech.2017.05.048

  日期：2017.9

  The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders. Compounds from this series were demonstrated to be potent inhibitors of the lytic action of both isolated recombinant perforin and perforin secreted by natural killer cells in vitro. Several potent and soluble examples were assessed for in vivo pharmacokinetic properties and found to be suitable for progression to an in vivo model of transplant rejection. (C) 2017 The Authors. Published by Elsevier Masson SAS.