(S)-N-[3,4-dihydroxybutyl]-5-[1-(2-(methoxymethyl)-pyrrolidinyl)sulfonyl]isatin | 1160524-59-3

• 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)-N-[3,4-dihydroxybutyl]-5-[1-(2-(methoxymethyl)-pyrrolidinyl)sulfonyl]isatin
• 英文别名: (S)-1-(3,4-dihydroxybutyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin；(S)-1-(3,4-Dihydroxybutyl)-5-[1-(2-methoxymethylpyrrolidinyl)-sulfonyl]isatin；1-(3,4-dihydroxybutyl)-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 1160524-59-3
• 化学式: C₁₈H₂₄N₂O₇S
• 分子量: 412.464
• InChiKey: RBQBJJBLAZNQJZ-UEWDXFNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]-1-[2-(oxiran-2-yl)ethyl]isatin 在 甲醇 、 silica gel 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以29 mg的产率得到(S)-N-[3,4-dihydroxybutyl]-5-[1-(2-(methoxymethyl)-pyrrolidinyl)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

文献信息

• Synthesis, ¹⁸F-Radiolabeling, and in Vivo Biodistribution Studies of <i>N</i>-Fluorohydroxybutyl Isatin Sulfonamides using Positron Emission Tomography
  作者：Panupun Limpachayaporn、Stefan Wagner、Klaus Kopka、Sven Hermann、Michael Schäfers、Günter Haufe

  DOI：10.1021/jm400257a

  日期：2013.6.13

  respectively), which makes them appropriate PET radiotracer candidates. Therefore, N-(4-[18F]fluoro-3(R)-hydroxybutyl)- and N-(3(S)-[18F]fluoro-4-hydroxybutyl)-5-[1-(2(S)-(methoxymethyl)pyrrolidinyl)sulfonyl]isatin were synthesized in 140 min with 24% and 10% overall radiochemical yields and specific activities of 10–127 GBq/μmol using [18F]fluoride in the presence of Kryptofix and subsequent acidic hydrolysis

  caspases-3和-7效应子在程序化的I型细胞死亡（细胞凋亡）中起着核心作用。使用正电子发射断层扫描（PET）通过跟踪执行胱天蛋白酶的活性进行的分子成像可能允许检测早期发作以及对细胞凋亡失调引起的各种疾病进行治疗监测。在此，通过用氟化物使环硫酸盐开环，制备了四种新的基于氟化的非对映体和对映体纯和对映体纯的异磺酰胺磺胺类强效和选择性caspase-3和-7抑制剂。所有的氟代醇都表现出出色的体外亲和力（对于caspase-3和-7的IC 50分别高达11.8和0.951 nM），这使其成为合适的PET放射性示踪剂。因此，N-（4- [ 18 F] fluoro-3（R）-N-（3（S）-[ 18 F]氟-4-羟基丁基）-5- [1-（2（S）-（甲氧基甲基）吡咯烷基）磺酰基] isatin的合成在140分钟内完成，在存在Kryptofix并随后进行酸性水解的情况下，使用[ 18 F]氟化物
• 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.