(Z)-3-(4-(dimethylamino)benzylidene)indolin-2-one | 90828-16-3

• 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: (Z)-3-(4-(dimethylamino)benzylidene)indolin-2-one
• 英文别名: SU4312；(Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one；DMBI；3-(4-dimethylamino-benzylidene)-1,3-dihydro-indol-2-one；3-(4-dimethylamino-benzylidene)-indolin-2-one；3-(4-Dimethylamino-benzyliden)-indolin-2-on；3-(4-(Dimethylamino)benzylidene)-1,3-dihydro-2H-indol-2-one；(3Z)-3-[[4-(dimethylamino)phenyl]methylidene]-1H-indol-2-one
• CAS: 90828-16-3
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: UAKWLVYMKBWHMX-PTNGSMBKSA-N

物化性质

• 沸点：
  497.1±45.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Z)-3-(4-(dimethylamino)benzylidene)indolin-2-one 反应 0.08h， 以51%的产率得到(E)-3-(4-(dimethylamino)benzylidene)indolin-2-one
  参考文献：
  名称：

  （Z）-和（E）-亚芳基-1,3-二氢吲哚-2-酮：构型，构型和红外羰基拉伸频率

  摘要：

  研究了（Z）-和（E）-亚芳基-1,3-二氢吲哚-2-酮的构型和构象。在固态下，Z-异构体是平面的，而E-异构体的芳基明显扭曲，如两个X射线结构所示。发现（c o）与取代基的σp +之间存在线性关系，这可以推断溶液中的构象以及Ar–C C–C O系统的共轭程度。

  DOI：

  10.1039/p29840000615
• 作为产物：
  描述：

  靛红 在 哌啶 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 52.0h， 生成 (Z)-3-(4-(dimethylamino)benzylidene)indolin-2-one
  参考文献：
  名称：

  Synthesis and anti-tyrosine kinase activity of 3-(substituted-benzylidene)-1, 3-dihydro-indolin derivatives: investigation of their role against p60c-Src receptor tyrosine kinase with the application of receptor docking studies

  摘要：

  A series of 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-thione derivatives were synthesized as modified congeners of 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one series. All the synthesized compounds were examined for their in vitro anti-tyrosine kinase activity against p60c-Src. The activity results revealed that compounds (Z)-3-(4'-Dimethylamino-benzylidene)-1, 3-dihydro-indolin-2-thione (12) (E)-3-(2', 6'-Dichloro-benzylidene)-1, 3-dihydro-indolin-2-thione (13) and (E)-3-(3'-Hydroxy-4'-methoxy-benzylidene)-1, 3-dihydro-indolin-2-thione (19) exhibited anti-tyrosine kinase activity with IC50 value of 21.91, 21.20 and 30.92 microM, respectively. These results are comparable to PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3, 4-d]pyrimidine-4-yl-amine] (IC50=0.17 microM), which is reported as a potent and selective p60c-Src tyrosine kinase inhibitor. Some thio congeners are found to be more potent than oxo derivatives; however, no significant correlation was observed between the activity profiles of these two series. Docking program was used to investigate the docking mode of each compound at the active site. Among all of the compounds, only (Z)-3-(2'-Chloro-benzylidene)-1, 3-dihydro-indolin-2-one (8) and (E)-3-(3'-Nitro-benzylidene)-1, 3-dihydro-indolin-2-thione (16) were docked at the active site where the PP1 was embedded.

  DOI：

  10.1016/j.farmac.2005.01.015

文献信息

• Design, Synthesis and Biological Evaluation of Oxindole-Based Chalcones as Small-Molecule Inhibitors of Melanogenic Tyrosinase
  作者：Sharad Kumar Suthar、Sumit Bansal、Niteen Narkhede、Manju Guleria、Angel Treasa Alex、Alex Joseph

  DOI：10.1248/cpb.c17-00301

  日期：——

  The enzyme tyrosinase regulates melanogenesis and skin hyperpigmentation by converting L-3,4-dihydroxyphenylalanine (L-DOPA) into dopaquinone, a key step in the melanin biosynthesis. The present work deals with design and synthesis of various oxindole-based chalcones as monophenolase and diphenolase activity inhibitors of tyrosinase. Among the screened compounds, 4-hydroxy-3-methoxybenzylidene moiety

  酪氨酸酶通过将L-3,4-二羟基苯丙氨酸（L-DOPA）转化为多巴醌来调节黑色素生成和皮肤色素沉着，这是黑色素生物合成的关键步骤。本工作涉及设计和合成各种基于羟吲哚的查耳酮作为酪氨酸酶的单酚酶和双酚酶活性抑制剂。在筛选出的化合物中，通过羟吲哚和香草醛的一锅反应制备的带有查尔酮的4-羟基-3-甲氧基亚苄基部分（7）在单酚酶和双酚酶活性测定中显示出最高的抗酪氨酸酶活性，IC50分别为63.37和59.71 µM。在分子对接研究中，在所有对接的配体中，查耳酮7对酪氨酸酶的结合亲和力最高，而估计的结合自由能最低。
• Investigation of triazole-linked indole and oxindole glycoconjugates as potential anticancer agents: novel Akt/PKB signaling pathway inhibitors
  作者：Atulya Nagarsenkar、Santosh Kumar Prajapti、Sravanthi Devi Guggilapu、Swetha Birineni、Sudha Sravanti Kotapalli、Ramesh Ummanni、Bathini Nagendra Babu

  DOI：10.1039/c5md00513b

  日期：——

  assay, the results indicated that compounds 5f (indole derivative) and E-9b (oxindole derivative) displayed remarkable cytotoxic activity against DU145 cells. Moreover, the colony formation assay (soft agar assay) revealed that compounds 5f and E-9b can inhibit the growth and proliferation of DU145 cells. The impact of the most active cytotoxic compounds 5f and E-9b on the cell cycle distribution was

  为了继续进行新型生物活性剂的合成，我们从吲哚/羟吲哚（29种化合物）合成了两组三唑连接的糖缀合物，并通过IR（红外光谱），1 H NMR（核磁共振）进行了进一步表征，13 C NMR和质谱分析。评估了新合成的目标化合物对DU145（前列腺癌），HeLa（宫颈癌），A549（肺癌）和MCF-7（乳腺癌）细胞系的初步体外抗癌活性。在磺基罗丹明B（SRB）分析中，结果表明化合物5f（吲哚衍生物）和E -9b（羟吲哚衍生物）对DU145细胞显示出显着的细胞毒活性。此外，集落形成测定法（软琼脂测定法）表明化合物5f和E -9b可以抑制DU145细胞的生长和增殖。在DU145细胞中评估了活性最高的细胞毒性化合物5f和E -9b对细胞周期分布的影响，该细胞在亚G1期表现出细胞周期停滞。接下来，化合物5f和E -9b对DU145细胞中的半胱天冬酶激活进行了测试，结果表明这些化合物具有通过内在途径诱导细胞凋
• Synthesis and Biological Evaluations of 3-Substituted Indolin-2-ones:  A Novel Class of Tyrosine Kinase Inhibitors That Exhibit Selectivity toward Particular Receptor Tyrosine Kinases
  作者：Li Sun、Ngoc Tran、Flora Tang、Harald App、Peter Hirth、Gerald McMahon、Cho Tang

  DOI：10.1021/jm980123i

  日期：1998.7.1

  analysis for these compounds and their relative potency and selectivity to inhibit particular RTKs has determined that (1) 3-[(five-membered heteroaryl ring)methylidenyl]indolin-2-ones are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C-3 position of indolin-2-ones showed high selectivity toward

  已经设计并合成了3-取代的吲哚-2-酮，作为一类新型的酪氨酸激酶抑制剂，该抑制剂对不同的受体酪氨酸激酶（RTK）具有选择性。已经评估了这些化合物对完整细胞中一组RTK的相对抑制特性。通过修饰3-取代的吲哚-2-酮，我们鉴定了在亚微摩尔水平下显示选择性抑制各种RTK的配体依赖性自磷酸化的化合物。这些化合物的结构活性分析及其抑制特定RTK的相对效能和选择性已确定（1）3-[（（五元杂芳基环）亚甲基]茚满-2-酮对VEGF（Flk-1 ）RTK活动，（2）在吲哚-2-酮的C-3位的C-3位置的苯环中含有庞大基团的3-（取代的苄基）吲哚啉-2-酮显示出对EGF和Her-2 RTK的高选择性，并且（ 3）在针对PDGF和VEGF（Flk-1）RTK进行测试时，在吲哚-2-酮（16）的C-3位置包含延伸的侧链的化合物表现出较高的效价和选择性。这些3-取代的吲哚-2-酮中的两个的最近公布的晶体学数据提供
• Method of treating cancers with SAHA and pemetrexed
  申请人：Pluda James

  公开号：US20070117815A1

  公开（公告）日：2007-05-24

  The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof, and a second amount of an anti-cancer agent. The HDAC inhibitor and the anti-cancer agent may be administered to comprise therapeutically effective amounts. In various aspects, the effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.

  本发明涉及一种治疗需要的受试者癌症的方法，通过向需要的受试者施用一定量的组蛋白去乙酰化酶（HDAC）抑制剂或其药用可接受的盐或水合物的第一量，以及一定量的抗癌药物。HDAC抑制剂和抗癌药物可以被施用以包含治疗有效量。在各种方面，HDAC抑制剂和抗癌药物的效果可能是相加的或协同的。
• Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents
  作者：Ankita Pathak、Vivek Pandey、Yuba Raj Pokharel、Vinod Devaraji、Abuzer Ali、Kashif Haider、Suma Saad、Rikeshwer Prasad Dewangan、Nadeem Siddiqui、M. Shahar Yar

  DOI：10.1016/j.bioorg.2021.105358

  日期：2021.11

  tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based

  双 TK 抑制剂已对许多肿瘤显示出显着的临床效果，但具有无法控制的副作用。这些抑制剂的设计方法和选择性在其效力和副作用方面起着重要作用。了解靶向受体中结合位点的同源性以及抑制后信号蛋白的参与可能有助于产生毒性较小但有效的抑制剂。在此，我们基于 VEGFR-2 和 EGFR 受体结合位点的同源性建模设计了亚苄基吲哚酮-2-one 衍生物，作为具有高选择性的双重抑制剂有效抗癌化合物。发现benzylideneindolon-2-one 衍生物以oxindole 的形式具有构象转换，在2-benzimidazole 处被取代。在合成的化合物中，发现5b在针对 VEGFR-2 和 EGFR的体外酶抑制试验，最高 IC 50值分别为6.81 ± 2.55和13.04 ± 4.07  nM。有趣的是，细胞毒性研究揭示了化合物5b对 A-431 细胞系（过度表达的 VEGFR-2 和 EGFR）增殖的选择性毒性，GI