ethyl (3RS,4'R)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate | 1236853-14-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (3RS,4'R)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate
• 英文别名: ethyl (4R)-2'-oxospiro[1,3-thiazolidine-2,3'-1H-indole]-4-carboxylate
• CAS: 1236853-14-7
• 化学式: C₁₃H₁₄N₂O₃S
• 分子量: 278.332
• InChiKey: KLUCCTBBTOJSTH-NKUHCKNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  BOC-L-脯氨酸 、 ethyl (3RS,4'R)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 ethyl (4'R)-3'-((tert-butoxycarbonyl)-L-prolyl)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate
  参考文献：
  名称：

  Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives

  摘要：

  Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and intramolecular cyclization reactions are suitable synthetic methods to generate chemically diverse diketopiperazine system, such as hexahydropyrrolo[1,2-a][1,3]thiazolo[3,2-d]pyrazine-5,10-dione (structure I), hexahydropyrrolo[1,2-a] [1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure II) and spiroindol-2-one[3,3']hexahydro-5,10H-pyrrolo[1,2-a][1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure III). Some of these compounds, especially those who belong to the series I and II, showed interesting cytotoxic activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.079
• 作为产物：
  描述：

  ethyl (4'R)-3'-((tert-butoxycarbonyl)-L-prolyl)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 120.0h， 以80%的产率得到ethyl (3RS,4'R)-2-oxospiro[indoline-3,2'-thiazolidine]-4'-carboxylate
  参考文献：
  名称：

  Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives

  摘要：

  Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and intramolecular cyclization reactions are suitable synthetic methods to generate chemically diverse diketopiperazine system, such as hexahydropyrrolo[1,2-a][1,3]thiazolo[3,2-d]pyrazine-5,10-dione (structure I), hexahydropyrrolo[1,2-a] [1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure II) and spiroindol-2-one[3,3']hexahydro-5,10H-pyrrolo[1,2-a][1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure III). Some of these compounds, especially those who belong to the series I and II, showed interesting cytotoxic activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.079

文献信息

• Identification of the Spiro(oxindole-3,3′-thiazolidine)-Based Derivatives as Potential p53 Activity Modulators
  作者：Isabel Gomez-Monterrey、Alessia Bertamino、Amalia Porta、Alfonso Carotenuto、Simona Musella、Claudio Aquino、Ilaria Granata、Marina Sala、Diego Brancaccio、Delia Picone、Carmine Ercole、Paola Stiuso、Pietro Campiglia、Paolo Grieco、Pio Ianelli、Bruno Maresca、Ettore Novellino

  DOI：10.1021/jm100838z

  日期：2010.12.9

  Here, we report the design of new analogues of spirooxoindolepyrrolidine nucleus as modulators of p53 activity. Compounds (3R,7aR)-6(4-chlorobenzyl)-1H-spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione (9c) and (3R,7aR)-5'-methyl-6-(3,4, 5-trimethoxybenzyl)-1H-spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione (10d) are the most potent compounds of this series, inhibiting cell growth of different human tumor cells at submicromolar and micromolar concentrations, respectively. Compound 9c induces apoptotic cell death in human melanoma cell line M14 at 24 h, while in the same condition, treatment with 10d showes a clear arrest at G2/M phase inducing delay of cell cycle progression. Possibly, these activities may be due to inhibition of p53-MDM2 interaction and subsequent p53 release and activation.
• Synthesis, in Vitro, and in Cell Studies of a New Series of [Indoline-3,2′-thiazolidine]-Based p53 Modulators
  作者：Alessia Bertamino、Maria Soprano、Simona Musella、Maria Rosaria Rusciano、Marina Sala、Ermelinda Vernieri、Veronica Di Sarno、Antonio Limatola、Alfonso Carotenuto、Sandro Cosconati、Paolo Grieco、Ettore Novellino、Maddalena Illario、Pietro Campiglia、Isabel Gomez-Monterrey

  DOI：10.1021/jm400311n

  日期：2013.7.11

  Analogues of the previously described spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione p53 modulators were prepared to explore new structural requirements at the thiazolidine domain for the antiproliferative activity and p53 modulation. In cell, antiproliferative activity was evaluated against two human tumor cell lines Derivative 5-bromo-3'-(cyclohexane carbonyl)-1-methyl-2-oxospiro[indoline-3,2'-thiazolidine] (4n) emerged as the most potent compound of this series inhibiting in vitro 30% of p53-MDM2 interaction at 5 mu M and the cell growth of different human tumor cells at nanomolar concentrations. Docking studies confirmed the interactions of 4n with the well-known Trp23 and Phe19 clefts, explaining the reasons for its binding affinity, for MDM2. 4n at 50 nM is capable of inducing the accumulation of p53 protein, inducing significant apoptotic,cell death without affecting the cell cycle progression. Comparative studies using nutlin in the same cellular system confirm the potential of 4n as a tool for increasing understanding of the process involved in the nontranscriptional proapoptotic activities of p53.
• Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives
  作者：Alessia Bertamino、Claudio Aquino、Marina Sala、Nicoletta de Simone、Carlo Andrea Mattia、Loredana Erra、Simona Musella、Pio Iannelli、Alfonso Carotenuto、Paolo Grieco

  DOI：10.1016/j.bmc.2010.04.079

  日期：2010.6.15

  Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and intramolecular cyclization reactions are suitable synthetic methods to generate chemically diverse diketopiperazine system, such as hexahydropyrrolo[1,2-a][1,3]thiazolo[3,2-d]pyrazine-5,10-dione (structure I), hexahydropyrrolo[1,2-a] [1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure II) and spiroindol-2-one[3,3']hexahydro-5,10H-pyrrolo[1,2-a][1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure III). Some of these compounds, especially those who belong to the series I and II, showed interesting cytotoxic activity. (C) 2010 Elsevier Ltd. All rights reserved.