4-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]benzonitrile | 79183-45-2

• 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: 4-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]benzonitrile
• 英文别名: 1-(4-cyano-benzyl)-indoline-2,3-dione；4-[(2,3-Dihydro-2,3-dioxo-1H-indol-1-yl)methyl]benzonitrile；4-[(2,3-dioxoindol-1-yl)methyl]benzonitrile
• CAS: 79183-45-2
• 化学式: C₁₆H₁₀N₂O₂
• 分子量: 262.268
• InChiKey: VKVDQDPNODPQTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]benzonitrile 在 sodium azide 、 水 、 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies

  摘要：

  A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 61, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-436 mu M, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (WPM) and increased levels of reactive oxygen species (ROS) were noted in A549 cells. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.017
• 作为产物：
  描述：

  苯胺 在 盐酸 、 盐酸羟胺 、 sodium hydride 、 sodium sulfate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methyl]benzonitrile
  参考文献：
  名称：

  Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies

  摘要：

  A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 61, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-436 mu M, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (WPM) and increased levels of reactive oxygen species (ROS) were noted in A549 cells. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.017

文献信息

• Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations
  作者：Wagdy M. Eldehna、Mahmoud A. El Hassab、Mahmoud F. Abo-Ashour、Tarfah Al-Warhi、Mahmoud M. Elaasser、Nesreen A. Safwat、Howayda Suliman、Marwa F. Ahmed、Sara T. Al-Rashood、Hatem A. Abdel-Aziz、Radwan El-Haggar

  DOI：10.1016/j.bioorg.2021.104748

  日期：2021.5

  treatments that target tumor cells in a selective manner. In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. The large tricyclic TBI motif is anticipated to achieve a plethora of hydrophobic

  在当前的医学时代，人类健康正面临着诸多挑战，尤其是人类恶性肿瘤。因此，通过以选择性方式靶向肿瘤细胞的新疗法，将无情地增强这些恶性肿瘤的治疗手段。在这方面，目前的工作旨在开发一组新的小分子，其特征是通过可切割的酰肼接头（7a-e和10a-i）与噻唑并 [3,2- a ] 苯并咪唑 ( TBI ) 基序缀合的特权靛红支架。) 作为潜在的抗癌 CDK2 抑制剂。大三环TBI预计基序将在 CDK2 结合位点内实现大量疏水相互作用。大多数制备的杂合体在IC 50范围内显着抑制了两种检测细胞系的生长；（2.60 ± 1.47–20.90 ± 1.17 µM，针对 MDA-MB-231）和（1.27 ± 0.06–16.83 ± 0.95 µM，针对 MCF-7）。特别是，杂种7a、7d和10a对所检查的细胞系显示出强大的双重活性，因此被选中用于进一步研究。除了在 MDA-MB-231 和 MCF-7
• Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation
  作者：Wagdy M. Eldehna、Ghada S. Hassan、Sara T. Al-Rashood、Hamad M. Alkahtani、Abdulrahman A. Almehizia、Ghada H. Al-Ansary

  DOI：10.3390/md18040190

  日期：——

  level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action

  从海洋中提取的多种吲哚和双吲哚已被确定为有前景的抗癌药物。在此，我们设计并合成了新型双吲哚系列 7a-f 和 9a-h 作为 Topsentin 和 Nortopsentin 类似物。我们的设计基于用更灵活的酰肼连接基取代天然引线中的杂环间隔基，同时保留两个外围吲哚环。检查所有合成的双吲哚对人乳腺癌（MCF-7 和 MDA-MB-231）细胞系的抗增殖作用。针对 MCF-7 细胞最有效的同源物 7e 和 9a（IC50 分别为 0.44 ± 0.01 和 1.28 ± 0.04 μM）可诱导 MCF-7 细胞凋亡（总凋亡百分比增加 23.7 倍和 16.8 倍），这一点显而易见通过膜联蛋白 V-FITC/PI 测定检测质膜磷脂酰丝氨酸的外化。这一证据得到了 Bax/Bcl-2 比率增加（与对照相比，18.65 倍和 11.1 倍）以及 caspase-3 水平（11.7 倍和 9.5 倍）和
• Discovery of natural product-like spirooxindole derivatives as highly potent and selective LSD1/KDM1A inhibitors for AML treatment
  作者：Chao Yang、Yuan Fang、Xiang Luo、Dehong Teng、Zhongqiu Liu、Yingtang Zhou、Guochao Liao

  DOI：10.1016/j.bioorg.2022.105596

  日期：2022.3

  natural LSD1 inhibitor higenamine, we herein performed further structure-based design, synthesis, and extensive structure–activity relationship (SAR) studies, affording structurally new spirooxindole derivatives. Particularly, FY-56 was identified to be a highly potent LSD1 inhibitor (IC50 = 42 nM) and showed high selectivity over monoamine oxidases (MAO-A/B). Mechanistic studies showed that FY-56 moderately

  组蛋白赖氨酸特异性去甲基化酶 1 (LSD1) 是一种很有前途的癌症治疗新靶点。在发现天然 LSD1 抑制剂去甲素后，我们在此进行了进一步的基于结构的设计、合成和广泛的构效关系 (SAR) 研究，提供了结构上新的螺氧吲哚衍生物。特别是，FY-56 被鉴定为一种高效的 LSD1 抑制剂（IC 50 = 42 nM) 并显示出对单胺氧化酶 (MAO-A/B) 的高选择性。机制研究表明，FY-56 适度抑制白血病细胞的增殖和克隆形成，诱导 H3K4me1/2 积累和 p53 活化，并降低转录因子 HOXA9 和 MEIS1 的 mRNA 水平。同时，FY-56 诱导 MOLM-13 和 MV4-11 细胞的分化，伴随着分化巨噬细胞和单核细胞特征性标志物的百分比增加。进一步的体内研究表明，FY-56 明显降低 CD45 + /CD33 +的比例外周血和脾脏中的白细胞，显着延长小鼠的存活率。总的来说，FY-56
• Indoloquinoxaline derivatives as promising multi-functional anti-Alzheimer agents
  作者：Ashish M. Kanhed、Dushyant V. Patel、Nirav R. Patel、Anshuman Sinha、Priyanka S. Thakor、Kishan B. Patel、Navnit K. Prajapati、Kirti V. Patel、Mange Ram Yadav

  DOI：10.1080/07391102.2020.1840441

  日期：2022.4.13

  Abstract To confront a disease like Alzheimer’s disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer’s disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed

  摘要 为了对抗阿尔茨海默病等具有复杂发病机制的疾病，多靶点定向配体的开发已成为一种有前途的药物发现方法。在我们致力于开发针对阿尔茨海默病的多靶点定向配体的过程中，设计并合成了一系列吲哚喹喔啉衍生物。体外胆碱酯酶抑制研究表明，所有合成的化合物都表现出中等至良好的胆碱酯酶抑制活性。6-(6-(Piperidin-1-yl)hexyl)-6 H -indolo[2,3- b ]quinoxaline 9f被确定为最有效和选择性的 BuChE 抑制剂 (IC 50= 0.96 µM，选择性指数 = 0.17)，与商业批准的参考药物多奈哌齐 (IC 50 = 1.87 µM)相比，BuChE 抑制活性高出 2 倍。此外，化合物9f还具有自诱导 Aβ 1-42聚集抑制活性（在 50 μM 浓度下抑制 51.24%）。该系列的一些化合物也显示出适度的抗氧化活性。为了解化合物9f的推定结合模式，进行了分子
• Synthesis, Spectroscopic Characterization and Antimicrobial Potential of Certain New Isatin-Indole Molecular Hybrids
  作者：Reem Al-Wabli、Azza Zakaria、Mohamed Attia

  DOI：10.3390/molecules22111958

  日期：——

  Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a-n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a-n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays

  分子杂交在药物化学中具有广泛的应用，以获得新的生物活性化合物。新的靛红-吲哚分子杂化物 5a-n 已被合成并通过各种光谱工具进行表征。使用抑菌圈直径 (DIZ) 和针对一组革兰氏阴性菌、革兰氏阳性菌和真菌的最低抑菌浓度 (MIC) 测定来评估所制备的化合物 5a-n 的体外抗菌潜力。大多数合成的化合物5a-n对革兰氏阴性菌表现出弱活性，而化合物5b和5c对革兰氏阳性菌表现出良好的活性。另一方面，化合物 5j 成为对白色念珠菌（C. albicans）最活跃的化合物，其 MIC 值为 3.9 µg/mL，化合物 5g 是对黑曲霉（A. niger）最活跃的同源物， MIC 值为 15.6 µg/mL。而且，化合物5h表现出最好的抗P。notatum 效应，MIC 值为 7.8 µg/mL，与化合物 5g 等效。