(E)-5-Styrylisatin | 132888-00-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-5-Styrylisatin
• 英文别名: 5-trans-styryl-indoline-2,3-dione；5-trans-Styryl-indolin-2,3-dion；5-[(E)-2-phenylethenyl]-1H-indole-2,3-dione
• CAS: 132888-00-7
• 化学式: C₁₆H₁₁NO₂
• 分子量: 249.269
• InChiKey: KJZBRZRRHIURGP-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 air 作用下， 生成 (E)-5-Styrylisatin
  参考文献：
  名称：

  Inhibition of monoamine oxidase by (E)-styrylisatin analogues

  摘要：

  Previous studies have shown that (E)-8-(3-chlorostyryl) caffeine (CSC) is a specific reversible inhibitor of human monoamine oxidase B (MAO-B) and does not bind to human MAO-A. Since the small molecule isatin is a natural reversible inhibitor of both MAO-B and MAO-A, (E)-5-styrylisatin and (E)-6-styrylisatin analogues were synthesized in an attempt to identify inhibitors with enhanced potencies and specificities for MAO-B. The (E)-styrylisatin analogues were found to exhibit higher binding affinities than isatin with the MAO preparations tested. The (E)-5-styrylisatin analogues bound more tightly than the (E)-6 analogue although the latter exhibits the highest MAO-B selectivity. Molecular docking studies with MAO-B indicate that the increased binding affinity exhibited by the (E)-styrylisatin analogues, in comparison to isatin, is best explained by the ability of the styrylisatins to bridge both the entrance cavity and the substrate cavity of the enzyme. Experimental support for this model is shown by the weaker binding of the analogues to the Ile199Ala mutant of human MAO-B. The lower selectivity of the (E)-styrylisatin analogues between MAO-A and MAO-B, in contrast to CSC, is best explained by the differing relative geometries of the aromatic rings for these two classes of inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.030

文献信息

• Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3
  作者：Maria Damgaard、Anas Al-Khawaja、Stine B. Vogensen、Andreas Jurik、Maarten Sijm、Maria E. K. Lie、Mathias I. Bæk、Emil Rosenthal、Anders A. Jensen、Gerhard F. Ecker、Bente Frølund、Petrine Wellendorph、Rasmus P. Clausen

  DOI：10.1021/acschemneuro.5b00150

  日期：2015.9.16

  Screening a library of small-molecule compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [H-3]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC50 values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacological characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a molecular modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes.
• Langenbeck et al., Journal fur praktische Chemie (Leipzig 1954), 1957, vol. <4> 4, p. 136,145
  作者：Langenbeck et al.

  DOI：——

  日期：——
• Inhibition of monoamine oxidase by (E)-styrylisatin analogues
  作者：Elizna M. Van der Walt、Erika M. Milczek、Sarel F. Malan、Dale E. Edmondson、Neal Castagnoli、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmcl.2009.03.030

  日期：2009.5

  Previous studies have shown that (E)-8-(3-chlorostyryl) caffeine (CSC) is a specific reversible inhibitor of human monoamine oxidase B (MAO-B) and does not bind to human MAO-A. Since the small molecule isatin is a natural reversible inhibitor of both MAO-B and MAO-A, (E)-5-styrylisatin and (E)-6-styrylisatin analogues were synthesized in an attempt to identify inhibitors with enhanced potencies and specificities for MAO-B. The (E)-styrylisatin analogues were found to exhibit higher binding affinities than isatin with the MAO preparations tested. The (E)-5-styrylisatin analogues bound more tightly than the (E)-6 analogue although the latter exhibits the highest MAO-B selectivity. Molecular docking studies with MAO-B indicate that the increased binding affinity exhibited by the (E)-styrylisatin analogues, in comparison to isatin, is best explained by the ability of the styrylisatins to bridge both the entrance cavity and the substrate cavity of the enzyme. Experimental support for this model is shown by the weaker binding of the analogues to the Ile199Ala mutant of human MAO-B. The lower selectivity of the (E)-styrylisatin analogues between MAO-A and MAO-B, in contrast to CSC, is best explained by the differing relative geometries of the aromatic rings for these two classes of inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.