(S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin | 220510-16-7

• 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: (S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin
• 英文别名: (S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione；Isatin Sulfonamide 34；1-benzyl-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 220510-16-7
• 化学式: C₂₆H₂₄N₂O₅S
• 分子量: 476.553
• InChiKey: PKOUAUWPBMZQCH-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 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：

  丙二腈 、 (S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin 以 甲醇 为溶剂， 反应 1.0h， 以88%的产率得到2-[1-benzyl-2-oxo-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1,2-dihydroindol-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：

  2-(苯氧基甲基)吡咯烷-1-羧酸-(S)-叔丁酯 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 (S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin
  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
• 作为试剂：
  描述：

  (S)-(+)-1-(methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin 、 溴甲苯 在 (S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin 、 hexanes-ether 作用下， 以to afford 152 mg (64%) of 2 as a yellow solid, mp 97.2-99.1° C的产率得到(S)-1-benzyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)isatin
  参考文献：
  名称：

  ISATIN ANALOGUES AND USES THEREFOR

  摘要：

  本发明揭示了新型异喹啉类似物，包括包含迈克尔受体（IMAs）的异喹啉类似物。还揭示了异喹啉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，并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）进行体内细胞凋亡成像。

  公开号：

  US20090068105A1

文献信息

• ISATIN DERIVATIVES FOR USE AS IN VIVO IMAGING AGENTS
  申请人：Aboabye Eric Ofori

  公开号：US20110195024A1

  公开（公告）日：2011-08-11

  Isatin 5-sulfonamide derivatives, pharmaceutical compositions comprising the derivatives, their use as molecular imaging agents, their use for the diagnosis or treatment of diseases or disorders associated with dysregulation of apoptosis, methods for synthesizing the derivatives, methods for the molecular imaging of caspase activity and apoptosis, and methods of assessing the therapeutic effect of a test substance on caspase activity are disclosed.

  异吲哚啉-5-磺酰胺衍生物，包括这些衍生物的药物组合物，它们作为分子成像剂的用途，它们用于与凋亡失调相关的疾病或紊乱的诊断或治疗，合成这些衍生物的方法，用于测定caspase活性和凋亡的分子成像方法，以及评估试验物质对caspase活性的治疗效果的方法。
• [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。
• Isatin analogues and uses therefor
  申请人：Washington University

  公开号：US08329686B2

  公开（公告）日：2012-12-11

  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).

  本发明揭示了新型异色酮类似物，包括包含迈克尔受体（IMAs）的异色酮类似物。进一步揭示了异色酮类似物的合成方法和用途，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）在体内成像细胞凋亡。
• Small molecule immunopotentiators and assays for their detection
  申请人：Novartis Vaccines and Diagnostics, Inc.

  公开号：EP2583678A2

  公开（公告）日：2013-04-24

  The invention provides immunostimulatory compositions comprising a small molecule immuno-potentiator (SMIP) compound and methods of administration thereof. Also provided are methods of administering a SMIP compound in an effective amount to enhance the immune response of a subject to an antigen. Further provided are novel compositions and methods of administering SMIP compounds alone or in combination with another agent for the treatment of cancer, infectious diseases and/or allergies/asthma. In a further aspect, the invention relates generally to methods of screening for small molecule immuno-modulatory compositions.

  本发明提供了包含小分子免疫促进剂（SMIP）化合物的免疫刺激组合物及其施用方法。还提供了施用有效量的 SMIP 化合物以增强受试者对抗原的免疫应答的方法。本发明还提供了单独施用 SMIP 化合物或与另一种制剂联合施用 SMIP 化合物以治疗癌症、传染性疾病和/或过敏/哮喘的新型组合物和方法。在另一方面，本发明一般涉及筛选小分子免疫调节组合物的方法。
• <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.