N-[4-(2-{[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butyl][2-(4-methanesulfonylaminophenoxy)ethyl]amino}ethyl)phenyl]methanesulfonamide | 944920-06-3

• 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-[4-(2-{[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butyl][2-(4-methanesulfonylaminophenoxy)ethyl]amino}ethyl)phenyl]methanesulfonamide
• 英文别名: N-[4-[2-[4-(1,3-dioxoisoindol-2-yl)butyl-[2-[4-(methanesulfonamido)phenoxy]ethyl]amino]ethyl]phenyl]methanesulfonamide
• CAS: 944920-06-3
• 化学式: C₃₀H₃₆N₄O₇S₂
• 分子量: 628.77
• InChiKey: HEIMTKLVXFGHKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  43
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  159
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-[4-(2-{[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butyl][2-(4-methanesulfonylaminophenoxy)ethyl]amino}ethyl)phenyl]methanesulfonamide 在 N,N-二异丙基乙胺 、 肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 24-{[(4-{[2-(4-Methanesulfonamidophenoxy)ethyl][2-(4-methanesulfonamidophenyl)ethyl]amino}butyl)carbamoyl]methyl}-5,5,27,27-tetramethyl-16-oxa-12,20-diazaheptacyclo[15.11.0.0^{3,15}.0^{4,12}.0^{6,11}.0^{20,28}.0^{21,26}]octacosa-1(28),2,4(12),6(11),7,9,21(26),22,24-nonaen-12-ylium-8-sulfonate
  参考文献：
  名称：

  Fluorescently Labeled Analogues of Dofetilide as High-Affinity Fluorescence Polarization Ligands for the Human Ether-a-go-go-Related Gene (hERG) Channel

  摘要：

  Novel fluorescent derivatives of dofetilide (1) have been synthesized. Analogues that feature a fluorescent probe attached through an aliphatic spacer to the central tertiary nitrogen of 1 have high affinity for the hERG channel, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 10e, which has hERG channel affinity equivalent to that of dofetilide. When bound to cell membranes expressing the hERG channel, 10e shows a robust increase in fluorescence polarization (FP) signal. In a FP binding assay using 10e as tracer ligand, K-i values for several known hERG channel blockers were measured and excellent agreement with the literature K-i values was observed over an affinity range of 2 nM to 3 mu M. 10e blocks hERG channel current in electrophysiological patch clamp experiments, and computational docking experiments predict that the dofetilide core of 10e binds hERG channel in a conformation similar to that previously predicted for 1. These analogues enable high-throughput hERG channel binding assays that are rapid, economical, and predictive of test compounds' potential for prolonged QT liabilities.

  DOI：

  10.1021/jm0700565
• 作为产物：
  描述：

  N-(4-溴丁基)邻苯二甲酰亚胺 、 N-去甲基多非利特 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以53%的产率得到N-[4-(2-{[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)butyl][2-(4-methanesulfonylaminophenoxy)ethyl]amino}ethyl)phenyl]methanesulfonamide
  参考文献：
  名称：

  Fluorescently Labeled Analogues of Dofetilide as High-Affinity Fluorescence Polarization Ligands for the Human Ether-a-go-go-Related Gene (hERG) Channel

  摘要：

  Novel fluorescent derivatives of dofetilide (1) have been synthesized. Analogues that feature a fluorescent probe attached through an aliphatic spacer to the central tertiary nitrogen of 1 have high affinity for the hERG channel, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 10e, which has hERG channel affinity equivalent to that of dofetilide. When bound to cell membranes expressing the hERG channel, 10e shows a robust increase in fluorescence polarization (FP) signal. In a FP binding assay using 10e as tracer ligand, K-i values for several known hERG channel blockers were measured and excellent agreement with the literature K-i values was observed over an affinity range of 2 nM to 3 mu M. 10e blocks hERG channel current in electrophysiological patch clamp experiments, and computational docking experiments predict that the dofetilide core of 10e binds hERG channel in a conformation similar to that previously predicted for 1. These analogues enable high-throughput hERG channel binding assays that are rapid, economical, and predictive of test compounds' potential for prolonged QT liabilities.

  DOI：

  10.1021/jm0700565