1-((4-benzylpiperazin-1-yl)methyl)indoline-2,3-dione | 83991-57-5

• 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-benzylpiperazin-1-yl)methyl)indoline-2,3-dione
• 英文别名: 1-[(4-Benzylpiperazin-1-yl)methyl]indole-2,3-dione
• CAS: 83991-57-5
• 化学式: C₂₀H₂₁N₃O₂
• mdl: MFCD00380784
• 分子量: 335.406
• InChiKey: BMIQFAZFVXOTTO-UHFFFAOYSA-N

物化性质

• 熔点：
  128-129 °C
• 沸点：
  499.1±55.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-N-(S-methyl)benzylbenzamide 、 1-((4-benzylpiperazin-1-yl)methyl)indoline-2,3-dione 以 四氢呋喃 为溶剂， 反应 6.0h， 以70%的产率得到4-[[1-[(4-benzylpiperazin-1-yl)methyl]-2-oxoindol-3-ylidene]amino]-N-[(1S)-1-phenylethyl]benzamide
  参考文献：
  名称：

  Discovery of Novel Isatin-Based p53 Inducers

  摘要：

  A series of isatin Schiff base derivatives were identified during in silk screening of the small molecule library for novel activators of p53. The compounds selected based on molecular docking results were further validated by a high-content screening assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. The hit compounds activated and stabilized p53, as shown by Western blotting, at higher rates than the well-known positive control Nutlin-3. Thus, the p53-activating compounds identified by this approach represent useful molecular probes for various cancer studies.

  DOI：

  10.1021/acsmedchemlett.5b00011
• 作为产物：
  描述：

  聚合甲醛 、 1-苄基哌嗪 、 靛红 以 乙醇 、 水 为溶剂， 反应 3.0h， 以76%的产率得到1-((4-benzylpiperazin-1-yl)methyl)indoline-2,3-dione
  参考文献：
  名称：

  A Study on Hydrolytic Stability of Isatin N-Mannich Bases

  摘要：

  Stability parameters of biologically active compounds with N-Mannich base motif in their structure, which is susceptible to hydrolysis, have been studied. A procedure for the synthesis of small molecule compounds reactivating the function of the p53 tumor suppressor protein was developed, and the dependence of the Mannich base degradation rate on the structure of the compounds was established. For the hydrolysis reaction we determined the rate constants and calculated rho, Delta G#, Delta H, and Delta S. Modifications of active compounds that retain the activity at the maximum possible stability were proposed.

  DOI：

  10.1134/s1070363218010085

文献信息

• COLLINO, F.;VOLPE, S., BOLL. CHIM. FARM., 1982, 121, N 5, 221-229
  作者：COLLINO, F.、VOLPE, S.

  DOI：——

  日期：——
• US5585378A
  申请人：——

  公开号：US5585378A

  公开（公告）日：1996-12-17
• [EN] ALDEHYDE DEHYDROGENASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'ALDÉHYDE DÉSHYDROGÉNASE ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2015084731A1

  公开（公告）日：2015-06-11

  The present disclosure provides compounds that are selective inhibitors of an ALDH isozyme. The present disclosure provides treatment methods that involve use of the selective inhibitors.
• A Study on Hydrolytic Stability of Isatin N-Mannich Bases
  作者：D. D. Orlova、D. S. Novikova、A. V. Garabadzhiu、V. G. Tribulovich

  DOI：10.1134/s1070363218010085

  日期：2018.1

  Stability parameters of biologically active compounds with N-Mannich base motif in their structure, which is susceptible to hydrolysis, have been studied. A procedure for the synthesis of small molecule compounds reactivating the function of the p53 tumor suppressor protein was developed, and the dependence of the Mannich base degradation rate on the structure of the compounds was established. For the hydrolysis reaction we determined the rate constants and calculated rho, Delta G#, Delta H, and Delta S. Modifications of active compounds that retain the activity at the maximum possible stability were proposed.
• Discovery of Novel Isatin-Based p53 Inducers
  作者：P. Davidovich、V. Aksenova、V. Petrova、D. Tentler、D. Orlova、S. Smirnov、V. Gurzhiy、A. L. Okorokov、A. Garabadzhiu、G. Melino、N. Barlev、V. Tribulovich

  DOI：10.1021/acsmedchemlett.5b00011

  日期：2015.8.13

  A series of isatin Schiff base derivatives were identified during in silk screening of the small molecule library for novel activators of p53. The compounds selected based on molecular docking results were further validated by a high-content screening assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. The hit compounds activated and stabilized p53, as shown by Western blotting, at higher rates than the well-known positive control Nutlin-3. Thus, the p53-activating compounds identified by this approach represent useful molecular probes for various cancer studies.