1-(4-iodobenzyl)-5-(2(S)-methoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione | 854251-32-4

• 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: 1-(4-iodobenzyl)-5-(2(S)-methoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
• 英文别名: (S)-1-(4-iodobenzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin；1-[(4-iodophenyl)methyl]-5-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 854251-32-4
• 化学式: C₂₁H₂₁IN₂O₅S
• 分子量: 540.379
• InChiKey: MBFCFVOWKKZRNA-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-iodobenzyl)-5-(2(S)-methoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione 、 六甲基二锡 在 四(三苯基膦)钯 作用下， 以 甲苯 为溶剂， 反应 0.08h， 以83%的产率得到5-(2(S)-methoxymethyl-pyrrolidine-l-sulfonyl)-1-(4-trimethylstannyl-benzyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  [EN] NOVEL IMAGING AGENTS COMPRISING CASPASE-3 INHIBITORS
  [FR] NOUVEAUX AGENTS D'IMAGERIE

  摘要：

  公开号：

  WO2005053752A3
• 作为产物：
  描述：

  L-脯氨醇 在 sodium hydride 、 三乙胺 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 1-(4-iodobenzyl)-5-(2(S)-methoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  5-Pyrrolidinylsulfonyl Isatins as a Potential Tool for the Molecular Imaging of Caspases in Apoptosis

  摘要：

  Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands ( CBRs). ( S)-5-[ 1-(2-Methoxymethylpyrrolidinyl) sulfonyl] isatin ( 7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibtion potencies in the nanomolar to subnanomolar range for caspase-3 ( K-i = 0.2- 56.1 nM). As shown for compound ( S)-1-( 4-(2-fluoroethoxy) benzyl)-5-[ 1( 2-methoxymethylpyrrolidinyl) sulfonyl] isatin ( 35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.

  DOI：

  10.1021/jm051217c

文献信息

• 5-PYRROLIDINYLSULFONYL-ISATIN DERIVATIVES
  申请人：Universitatsklinikum Munster

  公开号：US20130149239A1

  公开（公告）日：2013-06-13

  The present invention relates to novel 5 -pyrrolidinylsulfonyl isatin derivatives, non-peptidyl Caspase binding Radioligands (CbRs) and CbR-transporter conjugates derived from said isatin derivatives, diagnostic compositions comprising said compounds of the invention and their use for non-invasive diagnostic imaging.
• [EN] NOVEL IMAGING AGENTS COMPRISING CASPASE-3 INHIBITORS<br/>[FR] NOUVEAUX AGENTS D'IMAGERIE
  申请人：GE HEALTHCARE LTD

  公开号：WO2005053752A3

  公开（公告）日：2005-10-06
• 5-Pyrrolidinylsulfonyl Isatins as a Potential Tool for the Molecular Imaging of Caspases in Apoptosis
  作者：Klaus Kopka、Andreas Faust、Petra Keul、Stefan Wagner、Hans-Jörg Breyholz、Carsten Höltke、Otmar Schober、Michael Schäfers、Bodo Levkau

  DOI：10.1021/jm051217c

  日期：2006.11.1

  Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands ( CBRs). ( S)-5-[ 1-(2-Methoxymethylpyrrolidinyl) sulfonyl] isatin ( 7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibtion potencies in the nanomolar to subnanomolar range for caspase-3 ( K-i = 0.2- 56.1 nM). As shown for compound ( S)-1-( 4-(2-fluoroethoxy) benzyl)-5-[ 1( 2-methoxymethylpyrrolidinyl) sulfonyl] isatin ( 35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.