5-(azetidin-1-ylsulfonyl)indoline-2,3-dione | 220510-08-7

• 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: 5-(azetidin-1-ylsulfonyl)indoline-2,3-dione
• 英文别名: 1H-Indole-2,3-dione, 5-(1-azetidinylsulfonyl)-；5-(azetidin-1-ylsulfonyl)-1H-indole-2,3-dione
• CAS: 220510-08-7
• 化学式: C₁₁H₁₀N₂O₄S
• 分子量: 266.277
• InChiKey: VEHTUFDNCGHBFH-UHFFFAOYSA-N

物化性质

• 熔点：
  261.1-262.2 °C
• 密度：
  1.590±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  91.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-甲氧基溴苄 、 5-(azetidin-1-ylsulfonyl)indoline-2,3-dione 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 以55%的产率得到5-(azetidin-1-ylsulfonyl)-1-(4-methoxybenzyl)indoline-2,3-dione
  参考文献：
  名称：

  Synthesis and in Vitro Evaluation of Sulfonamide Isatin Michael Acceptors as Small Molecule Inhibitors of Caspase-6

  摘要：

  A key step in the onset of Huntington's disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments. Therefore. the inhibition of caspase-6 has been identified as a target for therapeutic drug development for the treatment of this disease. In this study a series of isatin sulfonamide Michael acceptors having a high nanomolar potency for inhibiting caspase-6 and increased selectivity for caspase-6 versus caspase-3 inhibition is reported.

  DOI：

  10.1021/jm900135r
• 作为产物：
  描述：

  5-isatinsulfonic acid sodium salt 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 环丁砜 、 氯仿 为溶剂， 反应 3.33h， 生成 5-(azetidin-1-ylsulfonyl)indoline-2,3-dione
  参考文献：
  名称：

  Potent and Selective Nonpeptide Inhibitors of Caspases 3 and 7

  摘要：

  5-Dialkylaminosulfonylisatins have been identified as potent, nonpeptide inhibitors of caspases 3 and 7. The most active compound within this series (34) inhibited caspases 3 and 7 in the 2-6 nM range and exhibited approximately 1000-fold selectivity for caspases 3 and 7 versus a panel of five other caspases (1, 2, 4, 6, and 8) and was at least 20-fold more selective versus caspase 9. Sequence alignments of the active site residues of the caspases strongly suggest that the basis of this selectivity is due to binding in the St subsite comprised of residues Tyr204, Trp206, and Phe256 which are unique to caspases 3 and 7. These compounds inhibit apoptosis in three cell-based models: human Jurkat T cells, human chondrocytes, and mouse bone marrow neutrophils.

  DOI：

  10.1021/jm0100537

文献信息

• [EN] CASPASES AND APOPTOSIS<br/>[FR] CASPASES ET APOPTOSE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001022966A1

  公开（公告）日：2001-04-05

  The present invention is to the novel compounds of Formula (I), their pharmaceutical compositions, and to the novel inhibition of caspases for use in the treatment of apoptosis, and disease states caused by excessive or inappropriate cell death.

  本发明涉及式（I）的新化合物、它们的制药组合物，以及用于治疗细胞凋亡和由过度或不适当的细胞死亡引起的疾病状态的新的半胱天冬酶抑制剂。
• CASPASES AND APOPTOSIS
  申请人：SmithKline Beecham Corporation

  公开号：EP1242081A1

  公开（公告）日：2002-09-25
• EP1242081A4
  申请人：——

  公开号：EP1242081A4

  公开（公告）日：2004-07-21
• US6403792B1
  申请人：——

  公开号：US6403792B1

  公开（公告）日：2002-06-11
• Potent and Selective Nonpeptide Inhibitors of Caspases 3 and 7
  作者：Dennis Lee、Scott A. Long、Jeffrey H. Murray、Jerry L. Adams、Mark E. Nuttall、Daniel P. Nadeau、Kristine Kikly、James D. Winkler、Chiu-Mei Sung、M. Dominic Ryan、Mark A. Levy、Paul M. Keller、Walter E. DeWolf

  DOI：10.1021/jm0100537

  日期：2001.6.1

  5-Dialkylaminosulfonylisatins have been identified as potent, nonpeptide inhibitors of caspases 3 and 7. The most active compound within this series (34) inhibited caspases 3 and 7 in the 2-6 nM range and exhibited approximately 1000-fold selectivity for caspases 3 and 7 versus a panel of five other caspases (1, 2, 4, 6, and 8) and was at least 20-fold more selective versus caspase 9. Sequence alignments of the active site residues of the caspases strongly suggest that the basis of this selectivity is due to binding in the St subsite comprised of residues Tyr204, Trp206, and Phe256 which are unique to caspases 3 and 7. These compounds inhibit apoptosis in three cell-based models: human Jurkat T cells, human chondrocytes, and mouse bone marrow neutrophils.