(S)-5-(2-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)-1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)indoline-2,3-dione | 1092522-46-7

• 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-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)-1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)indoline-2,3-dione
• 英文别名: (S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2-(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin；(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)pyrrolidine-1-sulfonyl)isatin；(S)-1-((1-(2-Fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin；5-[(2S)-2-[(2,4-difluorophenoxy)methyl]pyrrolidin-1-yl]sulfonyl-1-[[1-(2-fluoroethyl)triazol-4-yl]methyl]indole-2,3-dione
• CAS: 1092522-46-7
• 化学式: C₂₄H₂₂F₃N₅O₅S
• 分子量: 549.53
• InChiKey: XBILASWQSBQTIV-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (S)-5-(2-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)-1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)indoline-2,3-dione 、 1,3-丙二醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以58%的产率得到(S)-1-{1′-[1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl]-1′,2′-dihydro-2′-oxospiro(1,3-dioxane-2,3′-[3H]indol)-5′-sulfonyl}-2-(2,4-difluorophenoxymethyl)pyrrolidine
  参考文献：
  名称：

  JP5667056

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-5-(2-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)indoline-2,3-dione 在 copper(ll) sulfate pentahydrate 、 sodium hydride 、 sodium ascorbate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成 (S)-5-(2-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)-1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)indoline-2,3-dione
  参考文献：
  名称：

  Synthesis and evaluation of isatin analogs as caspase-3 inhibitors: Introduction of a hydrophilic group increases potency in a whole cell assay

  摘要：

  A series of isatin analogs containing a hydrophilic group, including a pyridine ring, ethylene glycol group, and a triazole ring, have been synthesized, and their inhibition potency for caspase-3 was measured both in vitro (i.e., recombinant enzyme) and in whole cells (HeLa cells). The analogs having a hydrophilic group, including 12, 13, 16, 38, and 40, have dramatically increased activity in vitro and in HeLa cells compared to the corresponding unsubstituted N-phenyl isatin analogs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.015

文献信息

• ISATIN DERIVATIVES FOR USE AS IN VIVO IMAGING AGENTS
  申请人：Aboabye Eric Ofori

  公开号：US20110195024A1

  公开（公告）日：2011-08-11

  Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.

  异吲哚啉-5-磺酰胺衍生物，包括这些衍生物的药物组合物，它们作为分子成像剂的用途，它们用于与凋亡失调相关的疾病或紊乱的诊断或治疗，合成这些衍生物的方法，用于测定caspase活性和凋亡的分子成像方法，以及评估试验物质对caspase活性的治疗效果的方法。
• Isatin derivatives for use as in vivo imaging agents
  申请人：Aboagye Eric Ofori

  公开号：US08961930B2

  公开（公告）日：2015-02-24

  Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.

  本发明公开了5-磺酰胺基异喹啉衍生物、包含该衍生物的制药组合物、其作为分子成像剂的应用、其用于诊断或治疗与细胞凋亡失调相关的疾病或疾病的方法、合成该衍生物的方法、测定caspase活性和细胞凋亡的分子成像方法以及评估测试物质对caspase活性的治疗效果的方法。
• Design, Synthesis, and Biological Characterization of a Caspase 3/7 Selective Isatin Labeled with 2-[¹⁸F]fluoroethylazide
  作者：Graham Smith、Matthias Glaser、Meg Perumal、Quang-De Nguyen、Bo Shan、Erik Årstad、Eric O. Aboagye

  DOI：10.1021/jm801107u

  日期：2008.12.25

  Imaging of programmed cell death (apoptosis) is important in the assessment of therapeutic response in oncology and for diagnosis in cardiac and neurodegenerative disorders. The executioner caspases 3 and 7 ultimately effect cellular death, thus providing selective molecular targets for in vivo quantification of apoptosis. To realize this potential, we aimed to develop F-18-labeled isatin sulfonamides with high metabolic,stability and moderate lipophilicity while retaining selectivity and affinity for caspase 3/7. A small library of isatins modified with fluorinated aromatic groups and heterocycles was synthesized. A lead compound incorporating 2'-fluoroethyl-1,2,3-triazole was identified with subnanomolar affinity for caspase 3. "Click labeling" provided the F-18-labeled tracer in 65 +/- 6% decay-corrected radiochemical yield from 2-[F-18]fluoroethylazide. The compound showed high stability in vivo with rapid uptake and elimination in healthy tissues and tumor. The novel F-18-labeled isatin is a candidate radiotracer for further preclinical evaluation for imaging of apoptosis.
• US8961930B2
  申请人：——

  公开号：US8961930B2

  公开（公告）日：2015-02-24
• [EN] ISATIN DERIVATIVES FOR USE AS IN VIVO IMAGING AGENTS<br/>[FR] DÉRIVÉS D'ISATINE POUR UTILISATION EN TANT QU'AGENTS D'IMAGERIE IN VIVO
  申请人：IMP INNOVATIONS LTD

  公开号：WO2010026388A1

  公开（公告）日：2010-03-11

  The present invention provides isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising said derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing said derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity.