(S)-5-((2-(methoxymethyl)pyrrolidin-1-yl)sulfonyl)-1-(prop-2-yn-1-yl)indoline-2,3-dione | 1292809-64-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-5-((2-(methoxymethyl)pyrrolidin-1-yl)sulfonyl)-1-(prop-2-yn-1-yl)indoline-2,3-dione
• 英文别名: (S)-5-{[2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}-1-(prop-2-yn-1-yl)indoline-2,3-dione；(S)-5-(2-(methoxymethyl)pyrrolidin-1-ylsulfonyl)-1-(prop-2-ynyl)indoline-2,3-dione
• CAS: 1292809-64-3
• 化学式: C₁₇H₁₈N₂O₅S
• 分子量: 362.406
• InChiKey: IFNRVCOTQLKFTM-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  83.99
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-5-((2-(methoxymethyl)pyrrolidin-1-yl)sulfonyl)-1-(prop-2-yn-1-yl)indoline-2,3-dione 、 叠氮苯 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 甲醇 、 水 为溶剂， 反应 72.0h， 以63%的产率得到(S)-5-(2-(methoxymethyl)pyrrolidin-1-ylsulfonyl)-1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)indoline-2,3-dione
  参考文献：
  名称：

  Isatin 1,2,3-triazoles as potent inhibitors against caspase-3

  摘要：

  Sixteen disubstituted 1,2,3-triazoles were prepared using the Huisgen cycloaddition reaction and evaluated as inhibitors against caspase-3. The two most potent inhibitors were found to be (S)-1-((1-(2,3-dihydrobenzo[ b][ 1,4] dioxin-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl)sulfonyl) indoline-2,3-dione (7f) and (S)-1-((1-benzyl-1H-1,2,3-triazol-5-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl) sulfonyl) indoline-2,3-dione (8g) with IC(50)-values of 17 and 9 nM, respectively. Lineweaver-Burk plots revealed that these two triazoles show competitive inhibitory mechanism against caspase-3. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.110
• 作为产物：
  描述：

  靛红 在 氯磺酸 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 氯仿 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 7.17h， 生成 (S)-5-((2-(methoxymethyl)pyrrolidin-1-yl)sulfonyl)-1-(prop-2-yn-1-yl)indoline-2,3-dione
  参考文献：
  名称：

  Isatin 1,2,3-triazoles as potent inhibitors against caspase-3

  摘要：

  Sixteen disubstituted 1,2,3-triazoles were prepared using the Huisgen cycloaddition reaction and evaluated as inhibitors against caspase-3. The two most potent inhibitors were found to be (S)-1-((1-(2,3-dihydrobenzo[ b][ 1,4] dioxin-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl)sulfonyl) indoline-2,3-dione (7f) and (S)-1-((1-benzyl-1H-1,2,3-triazol-5-yl)methyl)-5-((2-(methoxymethyl) pyrrolidin-1-yl) sulfonyl) indoline-2,3-dione (8g) with IC(50)-values of 17 and 9 nM, respectively. Lineweaver-Burk plots revealed that these two triazoles show competitive inhibitory mechanism against caspase-3. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.110

文献信息

• Synthesis and evaluation of a [18F]BODIPY-labeled caspase-inhibitor
  作者：Christian Paul Ortmeyer、Günter Haufe、Katrin Schwegmann、Sven Hermann、Michael Schäfers、Frederik Börgel、Bernhard Wünsch、Stefan Wagner、Verena Hugenberg

  DOI：10.1016/j.bmc.2017.02.033

  日期：2017.4

  BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective F-18-fluorination at the boron-core. Attached to a bioactive molecule and labeled with [F-18]fluorine, the resulting compounds are promising tracers for multimodal imaging in vivo and can be used for PET and fluorescence imaging. A BODIPY containing a phenyl and a hydroxy substituent on boron was synthesized and characterized. Fluorinated and hydroxy substituted dyes were coupled to an isatin-based caspase inhibitor via cycloaddition and the resulting compounds were evaluated in vitro in caspase inhibition assays. The metabolic stability and the formed metabolites were investigated by incubation with mouse liver microsomes and LC-MS analysis. Subsequently the fluorophores were labeled with [F-18]fluorine and an in vivo biodistribution study using dynamic PET was performed. (C) 2017 Elsevier Ltd. All rights reserved.
• Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as potential PET tracers for in vivo imaging of activated caspases in apoptosis
  作者：Christopher M. Waldmann、Sven Hermann、Andreas Faust、Burkhard Riemann、Otmar Schober、Michael Schäfers、Günter Haufe、Klaus Kopka

  DOI：10.1016/j.bmc.2015.07.014

  日期：2015.9

  The programmed type I cell death, defined as apoptosis, is induced by complex regulated signaling pathways that trigger the intracellular activation of executioner caspases-3, -6 and -7. Once activated, these enzymes initiate cellular death through cleavage of proteins which are responsible for DNA repair, signaling and cell maintenance. Several radiofluorinated inhibitors of caspases-3 and -7, comprising a moderate lipophilic 5-(1-pyrrolidinylsulfonyl)isatin lead structure, are currently being investigated for imaging apoptosis in vivo by us and others. The purpose of this study was to increase the intrinsic hydrophilicity of the aforementioned lead structure to alter the pharmacokinetic behavior of the resulting caspase-3 and -7 targeted radiotracer. Therefore, fluorinated and non-fluorinated derivatives of 5-(1-pyrrolidinylsulfonyl)-7-azaisatin were synthesized and tested for their inhibitory properties against recombinant caspases-3 and -7. Fluorine-18 has been introduced by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of an alkyne precursor with 2-[F-18]fluoroethylazide. Using dynamic micro-PET biodistribution studies in vivo the kinetic behavior of one promising PET-compatible 5-pyrrolidinylsulfonyl 7-azaisatin derivative has been compared to a previously described isatin based radiotracer. (C) 2015 Elsevier Ltd. All rights reserved.