(S)-1-(2-fluoroallyl)-5-[(2-methoxymethylpyrrolidin-1-yl)sulfonyl]isatin | 1146968-88-8

• 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)-1-(2-fluoroallyl)-5-[(2-methoxymethylpyrrolidin-1-yl)sulfonyl]isatin
• 英文别名: (S)-1-(2-fluoroallyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin；1-(2-fluoroprop-2-enyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 1146968-88-8
• 化学式: C₁₇H₁₉FN₂O₅S
• 分子量: 382.413
• InChiKey: HCWVNDBXTZOJJT-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-1-(2-fluoroallyl)-5-[(2-methoxymethylpyrrolidin-1-yl)sulfonyl]isatin 在 N-溴代丁二酰亚胺(NBS) 、 氟化氢吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 以55%的产率得到(S)-1-(3-bromo-2,2-difluoropropyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin
  参考文献：
  名称：

  Fluorinated Isatin Derivatives. Part 2. New N-Substituted 5-Pyrrolidinylsulfonyl Isatins as Potential Tools for Molecular Imaging of Caspases in Apoptosis

  摘要：

  Caspases are responsible for the execution of the cell death program and are potentially suitable targets for the specific imaging of apoptosis in vivo. A series of N-1-substituted analogues of the small molecule nonpeptide caspase inhibitor (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (1), which may be useful for the development of caspase-targeted radioligands, were synthesized and their inhibition potencies were evaluated in vitro. Two of the most powerful techniques to introduce fluorine into organic compounds, viz, bromofluorination of olefins and fluorohydrin synthesis by ring-opening of epoxides, were used. Most of the target compounds are potent inhibitors of the two effector caspases-3 and -7. Furthermore, the F-18-radiolabeled model compound (S)-1-[4-(1-[F-18]fluoro-2-hydroxyethyl)benzyl]-5-[1-(2-methoxymethyl-pyrrolidinyl)sulfonyl]isatin ([F-18]37), a putative tracer for the noninvasive imaging of apoptosis by positron emission tomography (PET) was synthesized by nucleophilic epoxide ring-opening of its precursor 36. The radiochemistry utilized in the F-18-fluorination reverted to carrier-added [F-18]Et3N center dot 3HF, a new fluorine-18 source for radiolabeling.

  DOI：

  10.1021/jm8015014
• 作为产物：
  描述：

  5-[[（（2S）-2-（甲氧甲基）-1-吡咯烷基]磺酰基]-1H-吲哚-2,3-二酮 、 2-fluoroallyl tosylate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以44%的产率得到(S)-1-(2-fluoroallyl)-5-[(2-methoxymethylpyrrolidin-1-yl)sulfonyl]isatin
  参考文献：
  名称：

  氟化的靛红衍生物。第1部分：作为有效的caspase-3和-7抑制剂的新N-取代的（S）-5- [1-（2-（甲氧基甲基吡咯烷基）磺酰基] isatins的合成

  摘要：

  已合成并测试了一系列新的N-取代的（S）-5- [1-（2-（甲氧基甲基吡咯烷基）磺酰基] isatin衍生物，作为caspases-3和-7的抑制剂，已知它们是caspase-3和-7的关键酶。执行细胞凋亡。N-丙基-和N-丁基靛红，以及相应的端基醇和区域异构的氟丁基衍生物被证明是优秀的抑制剂，对caspases-3和-7具有不同的结合力。相反，相应的氟乙基和氟丙基化合物的活性低约100-1000倍。氟化的N-苄基靛红以及三氟烷基和二氟烷基衍生物是中等抑制剂。但是，在以下位置带有不同烷基醚基的isatinsN -1作为半胱氨酸蛋白酶3和-7的抑制剂非常弱或没有活性。

  DOI：

  10.1016/j.bmc.2009.02.048

文献信息

• Fluorinated isatin derivatives. Part 1: Synthesis of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatins as potent caspase-3 and -7 inhibitors
  作者：Anil Kumar Podichetty、Andreas Faust、Klaus Kopka、Stefan Wagner、Otmar Schober、Michael Schäfers、Günter Haufe

  DOI：10.1016/j.bmc.2009.02.048

  日期：2009.4

  N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives has been synthesized and tested as inhibitors of caspases-3 and -7, which are known to be downstream enzymes critical in the execution of apoptosis. N-Propyl- and N-butyl isatins, as well as the corresponding terminal alcohols and regioisomeric fluorobutyl derivatives were shown to be excellent inhibitors having different binding

  已合成并测试了一系列新的N-取代的（S）-5- [1-（2-（甲氧基甲基吡咯烷基）磺酰基] isatin衍生物，作为caspases-3和-7的抑制剂，已知它们是caspase-3和-7的关键酶。执行细胞凋亡。N-丙基-和N-丁基靛红，以及相应的端基醇和区域异构的氟丁基衍生物被证明是优秀的抑制剂，对caspases-3和-7具有不同的结合力。相反，相应的氟乙基和氟丙基化合物的活性低约100-1000倍。氟化的N-苄基靛红以及三氟烷基和二氟烷基衍生物是中等抑制剂。但是，在以下位置带有不同烷基醚基的isatinsN -1作为半胱氨酸蛋白酶3和-7的抑制剂非常弱或没有活性。
• Fluorinated Isatin Derivatives. Part 2. New <i>N</i>-Substituted 5-Pyrrolidinylsulfonyl Isatins as Potential Tools for Molecular Imaging of Caspases in Apoptosis
  作者：Anil K. Podichetty、Stefan Wagner、Sandra Schröer、Andreas Faust、Michael Schäfers、Otmar Schober、Klaus Kopka、Günter Haufe

  DOI：10.1021/jm8015014

  日期：2009.6.11

  Caspases are responsible for the execution of the cell death program and are potentially suitable targets for the specific imaging of apoptosis in vivo. A series of N-1-substituted analogues of the small molecule nonpeptide caspase inhibitor (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (1), which may be useful for the development of caspase-targeted radioligands, were synthesized and their inhibition potencies were evaluated in vitro. Two of the most powerful techniques to introduce fluorine into organic compounds, viz, bromofluorination of olefins and fluorohydrin synthesis by ring-opening of epoxides, were used. Most of the target compounds are potent inhibitors of the two effector caspases-3 and -7. Furthermore, the F-18-radiolabeled model compound (S)-1-[4-(1-[F-18]fluoro-2-hydroxyethyl)benzyl]-5-[1-(2-methoxymethyl-pyrrolidinyl)sulfonyl]isatin ([F-18]37), a putative tracer for the noninvasive imaging of apoptosis by positron emission tomography (PET) was synthesized by nucleophilic epoxide ring-opening of its precursor 36. The radiochemistry utilized in the F-18-fluorination reverted to carrier-added [F-18]Et3N center dot 3HF, a new fluorine-18 source for radiolabeling.