1-benzyl-5-(2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione | 872254-31-4

• 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-benzyl-5-(2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
• 英文别名: 1-benzyl-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 872254-31-4
• 化学式: C₂₅H₂₃N₃O₅S
• 分子量: 477.541
• InChiKey: PCWDXECMTMSSCD-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-benzyl-5-(2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione 、 丙二腈 以 甲醇 为溶剂， 反应 1.0h， 以75%的产率得到2-{1-benzyl-2-oxo-5-[2-(pyridine-3-yloxymethyl)-pyrrolidine-1-sulfonyl]-1,2-dihydro-indol-3-ylidene}-malononitrile
  参考文献：
  名称：

  Isatin Sulfonamide Analogs Containing a Michael Addition Acceptor:  A New Class of Caspase 3/7 Inhibitors

  摘要：

  A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.

  DOI：

  10.1021/jm070506t
• 作为产物：
  描述：

  (S)-2-(pyridin-3-yloxymethyl)pyrrolidine-1-carboxylic acid tert-butyl ester 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-benzyl-5-(2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  Isatin Sulfonamide Analogs Containing a Michael Addition Acceptor:  A New Class of Caspase 3/7 Inhibitors

  摘要：

  A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.

  DOI：

  10.1021/jm070506t

文献信息

• <i>N</i>-Benzylisatin Sulfonamide Analogues as Potent Caspase-3 Inhibitors:  Synthesis, in Vitro Activity, and Molecular Modeling Studies
  作者：Wenhua Chu、Jun Zhang、Chenbo Zeng、Justin Rothfuss、Zhude Tu、Yunxiang Chu、David E. Reichert、Michael J. Welch、Robert H. Mach

  DOI：10.1021/jm0506625

  日期：2005.12.1

  A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, were identified. These compounds were also observed to have a low potency for inhibiting the initiator caspases, caspase-1 and caspase-8, and caspase-6. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The results of the current study revealed a number of non-peptide-based caspase inhibitors that may be useful in assessing the role of inhibiting the executioner caspases in minimizing tissue damage in disease conditions characterized by unregulated apoptosis.