(2S,4R)-5-[1-(2-methoxymethyl-4-PEG₄yloxypyrrolidinyl)sulfonyl]isatin | 1445167-07-6

• 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: (2S,4R)-5-[1-(2-methoxymethyl-4-PEG₄yloxypyrrolidinyl)sulfonyl]isatin
• 英文别名: 5-[(2S,4R)-4-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl-1H-indole-2,3-dione
• CAS: 1445167-07-6
• 化学式: C₂₃H₃₄N₂O₁₀S
• 分子量: 530.596
• InChiKey: OWFZWHURDWQMOY-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  36
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,5,8,11-四氧杂十三烷-13-基4-甲基苯磺酸酯 在 锂硼氢 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 mineral oil 为溶剂， 反应 1.5h， 生成 (2S,4R)-5-[1-(2-methoxymethyl-4-PEG₄yloxypyrrolidinyl)sulfonyl]isatin
  参考文献：
  名称：

  Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7

  摘要：

  A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as F-18-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the mu M scale, whereas all 4-OPEG(4) (PEG(4) = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.011

文献信息

• Influence of 4- or 5-substituents on the pyrrolidine ring of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives on their inhibitory activities towards caspases-3 and -7
  作者：Panupun Limpachayaporn、Burkhard Riemann、Klaus Kopka、Otmar Schober、Michael Schäfers、Günter Haufe

  DOI：10.1016/j.ejmech.2013.04.011

  日期：2013.6

  A series of new 4- or 5-substituted pyrrolidine derivatives of 5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin bearing additional n-butyl or 4-fluorobutyl groups at the isatin nitrogen were prepared and their inhibitory activities have been tested against caspases-3 and -7, which are known to participate in the execution of the programmed cell death, called apoptosis. Several analogues fluorinated at the 4-position of the pyrrolidine ring were also synthesized since such inhibitors might be developed as F-18-radiotracers for molecular imaging of activated caspases in vivo by PET. Enantiomerically pure diastereomeric 4-fluoropyrrolidinyl derivatives inhibited the enzymes in the nanomolar scale, i.e.100-1000 times more efficient than the corresponding 4-methoxy analogues. The 4,4-difluorinated compound showed the best result with IC50 = 362 nM and 178 nM for the aforementioned caspases. In contrast, the 4-methoxy and 4-trifluoromethyl analogues exhibited less inhibition potencies for the enzymes in the mu M scale, whereas all 4-OPEG(4) (PEG(4) = tetraethyleneglycol) and 5-methoxymethyl derivatives were inactive. (C) 2013 Elsevier Masson SAS. All rights reserved.