(S)-(+)-1-(methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin | 220510-28-1

• 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: (S)-(+)-1-(methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin
• 英文别名: (S)-1-methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione；1-Methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1h-indole-2,3-dione；1-methyl-5-[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonylindole-2,3-dione
• CAS: 220510-28-1
• 化学式: C₂₀H₂₀N₂O₅S
• 分子量: 400.455
• InChiKey: PFAYCUAUBOGVDX-AWEZNQCLSA-N

物化性质

• 熔点：
  160.1-160.9 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  607.5±65.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 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-(methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin 以 甲醇 为溶剂， 反应 1.0h， 以87%的产率得到2-[1-methyl-2-oxo-5-(2-phenoxymethyl-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：

  L-脯氨醇 在 吡啶 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 (S)-(+)-1-(methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin
  参考文献：
  名称：

  5-Pyrrolidinylsulfonyl Isatins as a Potential Tool for the Molecular Imaging of Caspases in Apoptosis

  摘要：

  Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands ( CBRs). ( S)-5-[ 1-(2-Methoxymethylpyrrolidinyl) sulfonyl] isatin ( 7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibtion potencies in the nanomolar to subnanomolar range for caspase-3 ( K-i = 0.2- 56.1 nM). As shown for compound ( S)-1-( 4-(2-fluoroethoxy) benzyl)-5-[ 1( 2-methoxymethylpyrrolidinyl) sulfonyl] isatin ( 35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.

  DOI：

  10.1021/jm051217c

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

  公开号：WO1999006367A1

  公开（公告）日：1999-02-11

  (EN) 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.(FR) La présente invention concerne les nouveaux composés de formule (I), leurs compositions pharmaceutiques, ainsi que la nouvelle forme d'inhibition de caspases destinés à l'utilisation dans le traitement de l'apoptose et d'états pathogènes causés par une mort cellulaire excessive ou inappropriée.

  该发明涉及公式(I)的新化合物、它们的药物组合物，以及新的针对caspases的抑制剂，用于治疗由过度或不适当的细胞死亡引起的凋亡和疾病状态。
• 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。
• WO2006/74799
  申请人：——

  公开号：——

  公开（公告）日：——
• <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.