1-(4-hydroxy-benzyl)-5-[2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl]-1H-indole-2,3-dione | 946609-16-1

• 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-hydroxy-benzyl)-5-[2-(pyridin-3-yl-oxymethyl)-pyrrolidine-1-sulfonyl]-1H-indole-2,3-dione
• 英文别名: 1-[(4-hydroxyphenyl)methyl]-5-[(2S)-2-(pyridin-3-yloxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 946609-16-1
• 化学式: C₂₅H₂₃N₃O₆S
• 分子量: 493.54
• InChiKey: OCRBUZYTFNEEGD-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 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：
  126
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxy-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85%的产率得到2-{1-(4-hydroxy-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 四丁基氟化铵 、 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 1-(4-hydroxy-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

• ISATIN ANALOGUES AND USES THEREFOR
  申请人：Mach Robert H.

  公开号：US20090068105A1

  公开（公告）日：2009-03-12

  Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vivo imaging of apoptosis by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

  揭示了新颖的吲哚类似物，包括具有Michael受体的吲哚类似物（IMAs）。进一步揭示了吲哚类似物的合成方法，以及类似物的用途，包括抑制caspase-3和caspase-7，以及通过正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）对凋亡进行体内成像。
• 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。
• 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.