（3Z）-3-[[[4-（二甲基氨基）苯基]亚甲基]-1H-吲哚-2-酮 | 5812-07-7

• 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
• 中文名称: （3Z）-3-[[[4-（二甲基氨基）苯基]亚甲基]-1H-吲哚-2-酮
• 英文名称: SU4312
• 英文别名: 3-(4-(dimethylamino)benzylidene)indolin-2-one；3-(4-Dimethylamino-benzylidenyl)-2-indolinone；3-[[4-(dimethylamino)phenyl]methylidene]-1H-indol-2-one
• CAS: 5812-07-7
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: UAKWLVYMKBWHMX-UHFFFAOYSA-N

物化性质

• 熔点：
  225-232 °C
• 沸点：
  497.1±45.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为30 毫克/毫升

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

制备方法与用途

生物活性

SU4312 是 (Z)-SU4312 和 (E)-SU4312 的外消旋体。其中，(Z)-SU4312 抑制 PDGFR 和 FLK-1，IC50 分别为 19.4 μM 和 0.8 μM。(E)-SU4312 则抑制 PDGFR、FLK-1、EGFR、HER-2 和 IGF-1R，对应的 IC50 值分别为 24.2 μM、5.2 μM、18.5 μM、16.9 μM 和 10.0 μM。

靶点

| PDGFR | | Flk-1 |

体外研究

受体酪氨酸激酶 (RTKs) 已被证明是细胞信号转导的重要介质。许多 RTK 被发现是原癌基因的产物，提示它们在与人类癌症相关的变化过程中发挥着关键作用。

反应信息

• 作为反应物：
  描述：

  （3Z）-3-[[[4-（二甲基氨基）苯基]亚甲基]-1H-吲哚-2-酮 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 以75%的产率得到GIF-0726-r
  参考文献：
  名称：

  3-芳基吲哚酮衍生物作为抗疟原虫剂：合成、生物活性和计算分析

  摘要：

  摘要 疟疾是一种传染病，影响第三世界国家的弱势群体。受天然产物的启发，吲哚生物碱已被用作设计新抗疟药物的核心。因此，以中等至优异的产率获得了十八种羟吲哚衍生物、氮杂类似物。此外，通过H 2 /Pd/C 还原得到的羟吲哚和氮杂衍生物的饱和衍生物以良好的收率获得，导致每种化合物的外消旋混合物。接下来，测试了 18 种化合物对恶性疟原虫的抑制活性，发现 6 种化合物的 IC 50 < 20 µM。这些化合物中最活跃的是8c; 然而，它们的不饱和衍生物7c没有活性。然后，进行构效关系分析，发现LUMO叶聚焦在特定分子区与对恶性疟原虫的抑制活性有关。最后，我们使用分子对接虚拟筛选发现了羟吲哚衍生物对乳酸脱氢酶的潜在抑制作用。

  DOI：

  10.1080/14786419.2021.1895149
• 作为产物：
  描述：

  2-吲哚酮 、 对二甲氨基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 以95%的产率得到（3Z）-3-[[[4-（二甲基氨基）苯基]亚甲基]-1H-吲哚-2-酮
  参考文献：
  名称：

  3,3'-哌啶基螺氧杂吲哚的不对称合成和作为新的Hedgehog通路调节剂的立体特异性Cycloadducts的发现

  摘要：

  纪念Rolf Huisgen教授 抽象 亚烷基吲哚和2-氮杂-3-甲硅烷氧基-1,3-丁二烯的对映选择性杂Diels-Alder反应，由具有N，N'-二氧化物配体的二价过渡金属配合物催化，可有效地获得基于天然产物的3,3'-哌啶子基螺氧基吲哚类小分子。通过立体特异性环加成反应与Z-烯烃形成的exo-环加合物在刺猬信号通路的调节中显示出强大的活性。

  DOI：

  10.1055/s-0040-1707222

文献信息

• Simple, Efficient, and Green Method for Synthesis of Trisubstituted Electrophilic Alkenes Using Lipase as a Biocatalyst
  作者：Bhushan Nanasaheb Borse、Sanjeev Ramchandra Shukla、Yogesh Ashok Sonawane

  DOI：10.1080/00397911.2010.525334

  日期：2012.2.1

  Abstract A simple and efficient Knoevenagel condensation method for the synthesis of trisubstituted electrophilic alkenes was developed using lipase as a biocatalyst. Knoevenagel condensation was performed using the conventional method and using lipases (Aspergillus oryzae or Rhizopus oryzae) as biocatalysts, and reaction time, reaction temperature, yield, and recyclability were compared. Using a lipase

  摘要 以脂肪酶为生物催化剂，开发了一种简单高效的Knoevenagel缩合方法，用于合成三取代亲电烯烃。Knoevenagel缩合采用常规方法，以脂肪酶（米曲霉或米根霉）为生物催化剂，比较反应时间、反应温度、收率和可回收性。使用脂肪酶作为生物催化剂消除了对哌啶和吡啶等碱的需求。多种芳香醛和酮容易与活性亚甲基化合物缩合。后处理程序也非常简单，反应产率在75%到95%之间。两种生物催化剂都有效地循环了四次，产品的产率没有显着降低。脂肪酶显着的催化活性和可重复使用性扩大了其在 Knoevenagel 缩合中的适用性，在合成三取代的亲电烯烃时具有良好的收率。图形概要
• First Example of Lewis Acid Catalyzed 3-Substituted 5-Arylidene-1-methyl-2-thiohydantoin Formation
  作者：Brian Gregg、William Earley、Kathryn Golden、John Quinn、Dana Razzano、W. Rennells

  DOI：10.1055/s-2006-950342

  日期：——

  A survey of Lewis acids was conducted to facilitate the formation of arylidenethiohydantoins. The use of indium(III) trif­late shows significant advantages in facilitating this reaction. In most examples, the Lewis acid promoted catalysis gave shorter reaction times, higher conversion, and better purity profiles as compared to the traditional uncatalyzed reactions.

  对路易斯酸进行了调查，以促进亚芳基硫代海因的形成。三酸铟（III）的使用在促进该反应方面具有显著优势。在大多数实例中，与传统的非催化反应相比，路易斯酸催化反应的反应时间更短、转化率更高、纯度更好。
• Synthesis and radiopharmacological investigation of 3-[4′-[18F]fluorobenzylidene]indolin-2-one as possible tyrosine kinase inhibitor
  作者：Torsten Kniess、Ralf Bergmann、Manuela Kuchar、Jörg Steinbach、Frank Wuest

  DOI：10.1016/j.bmc.2009.09.038

  日期：2009.11

  The radiosynthesis and radiopharmacological evaluation of 3-[4'-[F-18] fluorobenzylidene]indolin-2-one, a derivative of tyrosine kinase inhibitor SU5416, is described. The radiosynthesis was accomplished by Knoevenagel condensation of 4-[F-18]fluorobenzaldehyde with oxindole in a remotely controlled synthesis module. The reaction conditions were optimized through screening the influence of different bases on the radiochemical yield. The radiotracer was obtained after a two-step labelling procedure in 4% decay-corrected radiochemical yield at a specific activity of 48-61 GBq/mu mol within 90 min. The radiochemical purity after semi-preparative HPLC purification exceeded 98%.The biodistribution was studied in Wistar rats. After distribution the radiotracer was rapidly accumulated in the adrenals, liver and kidneys, however, it was cleared from these and the most other organs. Only the adipose tissue remained the activity over 60 min. Unexpected high transient uptake was observed in the brain, pancreas, heart and lung. The fast clearance of 3-[4'-[F-18] fluorobenzylidene] indolin-2-one was caused by excretion, approximately one half each was renal and biliary excreted and the other part cleared by metabolic processes. In arterial blood plasma two more polar metabolites were found by radio-HPLC. After 20 min post-injection, only 12% of intact radiotracer has been detected. Consequently, in small animal PET studies with FaDu tumour bearing mice no specific uptake in the tumours could be observed. (C) 2009 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Characterization of 3-(Benzylidene)indolin-2-one Derivatives as Ligands for α-Synuclein Fibrils
  作者：Wenhua Chu、Dong Zhou、Vrinda Gaba、Jialu Liu、Shihong Li、Xin Peng、Jinbin Xu、Dhruva Dhavale、Devika P. Bagchi、André d’Avignon、Naomi B. Shakerdge、Brian J. Bacskai、Zhude Tu、Paul T. Kotzbauer、Robert H. Mach

  DOI：10.1021/acs.jmedchem.5b00571

  日期：2015.8.13

  A series of 3-(benzylidine)indolin-2-one derivatives were synthesized and evaluated for their in vitro binding to alpha synuclein (alpha-syn), beta amyloid (A beta), and tau fibrils. Compounds with a single double bond in the 3-position had only a modest affinity for alpha-syn and no selectivity for alpha-syn versus A beta or tau fibrils. Homologation to the corresponding diene analogues yielded a mixture of Z,E and E,E isomers; substitution of the indoline nitrogen with an N-benzyl group resulted in increased binding to alpha-syn and reasonable selectivity for alpha-syn versus and tau. Introduction of a para-nitro group into the benzene ring of the diene enabled separation of the Z,E and E,E isomers and led to the identification of the Z,E configuration as the more active regioisomer. The data described here provide key structural information in the design of probes which bind preferentially to alpha-syn versus A beta or tau fibrils.
• Asymmetric Synthesis of 3,3′-Piperidinoyl Spirooxindoles and Discovery of Stereospecific Cycloadducts as Novel Hedgehog Pathway Modulators
  作者：Kamal Kumar、Mohammad Rehan、Jana Flegel、Franziska Heitkamp、Jorgelina L. Pergomet、Felix Otte、Carsten Strohmann

  DOI：10.1055/s-0040-1707222

  日期：2020.11

  transition metal complexes with N,N′-dioxide ligands offered an efficient access to natural-product-based 3,3′-piperidinoyl spiroox­indole class of small molecules. exo-Cycloadducts formed via stereospecific cycloaddition with Z-olefin displayed potent activity in modulation of hedgehog pathway.

  纪念Rolf Huisgen教授 抽象 亚烷基吲哚和2-氮杂-3-甲硅烷氧基-1,3-丁二烯的对映选择性杂Diels-Alder反应，由具有N，N'-二氧化物配体的二价过渡金属配合物催化，可有效地获得基于天然产物的3,3'-哌啶子基螺氧基吲哚类小分子。通过立体特异性环加成反应与Z-烯烃形成的exo-环加合物在刺猬信号通路的调节中显示出强大的活性。