1-(4-甲氧基苄基)-5-({(2S)-2-[(3-吡啶基氧基)甲基]-1-吡咯烷基}磺酰基)-1H-吲哚-2,3-二酮 | 872254-32-5

• 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
• 中文名称: 1-(4-甲氧基苄基)-5-({(2S)-2-[(3-吡啶基氧基)甲基]-1-吡咯烷基}磺酰基)-1H-吲哚-2,3-二酮
• 英文名称: 1-(4-methoxybenzyl)-5-({(2S)-2-[(3-pyridinyloxy)methyl]-1-pyrrolidinyl}sulfonyl)-1H-indole-2,3-dione
• 英文别名: 1-(4-methoxybenzyl)-5-(2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione；1-(4-Methoxybenzyl)-5-[2-(pyridin-3-yl-oxymethyl)pyrrolidine-1-sulfonyl]-1H-indole-2,3-dione；1-[(4-methoxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 872254-32-5
• 化学式: C₂₆H₂₅N₃O₆S
• 分子量: 507.567
• InChiKey: XDHJBIYJRNFDKS-IBGZPJMESA-N

物化性质

• 熔点：
  156.7-158.4 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  732.1±70.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苄基)-5-({(2S)-2-[(3-吡啶基氧基)甲基]-1-吡咯烷基}磺酰基)-1H-吲哚-2,3-二酮 、 丙二腈 以 甲醇 为溶剂， 反应 1.0h， 以82%的产率得到2-{1-(4-methoxy-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 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 1-(4-甲氧基苄基)-5-({(2S)-2-[(3-吡啶基氧基)甲基]-1-吡咯烷基}磺酰基)-1H-吲哚-2,3-二酮
  参考文献：
  名称：

  N-Benzylisatin Sulfonamide Analogues as Potent Caspase-3 Inhibitors:  Synthesis, in Vitro Activity, and Molecular Modeling Studies

  摘要：

  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.

  DOI：

  10.1021/jm0506625

文献信息

• Compound for treatment of myotonic dystrophy type 1
  申请人：Universitat De València, Estudi General

  公开号：EP3034074A1

  公开（公告）日：2016-06-22

  The present invention relates to a compound, or a salt thereof, and a pharmaceutical composition comprising said compound, or a salt thereof, for use in the prevention and/or treatment of myotonic dystrophy type 1 in a patient, in particular by reducing the levels of autophagy and apoptosis that are elevated in myotonic muscular dystrophy type 1.

  本发明涉及一种化合物或其盐，以及包含所述化合物或其盐的药物组合物，用于预防和/或治疗患者的肌营养不良症1型，特别是通过降低肌营养不良症1型中升高的自噬和细胞凋亡水平。
• <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.
• COMPOUND FOR TREATMENT OF MYOTONIC DYSTROPHY TYPE 1
  申请人：Universitat De València, Estudi General

  公开号：EP3233073A1

  公开（公告）日：2017-10-25
• [EN] COMPOUND FOR TREATMENT OF MYOTONIC DYSTROPHY TYPE 1<br/>[FR] COMPOSÉ POUR LE TRAITEMENT D'UNE DYSTROPHIE MYOTONIQUE DE TYPE 1
  申请人：UNI DE VALÈNCIA ESTUDI GENERAL

  公开号：WO2016097299A1

  公开（公告）日：2016-06-23

  Compound for treatment of myotonic dystrophy type The present invention relates to a compound, or a salt thereof, and a pharmaceutical composition comprising said compound, or a salt thereof, for use in the prevention and/or treatment of myotonic dystrophy type 1 in a patient, in particular by reducing the levels of autophagy and apoptosis that are elevated in myotonic muscular dystrophy type 1.
• Isatin Sulfonamide Analogs Containing a Michael Addition Acceptor:  A New Class of Caspase 3/7 Inhibitors
  作者：Wenhua Chu、Justin Rothfuss、André d'Avignon、Chenbo Zeng、Dong Zhou、Richard S. Hotchkiss、Robert H. Mach

  DOI：10.1021/jm070506t

  日期：2007.7.1

  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.