N-[2-(1,3-dihydro-1,3-dioxo-2h-isoindol-2-yl)-1,1-dimethylethyl]carbamic acid 1,1-dimethylethyl ester | 1373437-43-4

• 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-[2-(1,3-dihydro-1,3-dioxo-2h-isoindol-2-yl)-1,1-dimethylethyl]carbamic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[1-(1,3-dioxoisoindol-2-yl)-2-methylpropan-2-yl]carbamate
• CAS: 1373437-43-4
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: HQQZPRGRCQWGBJ-UHFFFAOYSA-N

物化性质

• 沸点：
  453.2±28.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.71
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-[2-(1,3-dihydro-1,3-dioxo-2h-isoindol-2-yl)-1,1-dimethylethyl]carbamic acid 1,1-dimethylethyl ester 在 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 2-N-boc-2-甲基-1,2-丙二胺
  参考文献：
  名称：

  Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines

  摘要：

  We report the synthesis and biological evaluation of a series of novel alpha-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 mu g kg(-1) at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.067
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 生成 N-[2-(1,3-dihydro-1,3-dioxo-2h-isoindol-2-yl)-1,1-dimethylethyl]carbamic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines

  摘要：

  We report the synthesis and biological evaluation of a series of novel alpha-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 mu g kg(-1) at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.067