5-bromo-1-(2-bromoethyl)indoline-2,3-dione | 941867-00-1

• 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: 5-bromo-1-(2-bromoethyl)indoline-2,3-dione
• 英文别名: 5-bromo-1-(2-bromoethyl)-1H-indole-2,3-dione；5-bromo-1-(2-bromoethyl)indole-2,3-dione
• CAS: 941867-00-1
• 化学式: C₁₀H₇Br₂NO₂
• mdl: MFCD08273585
• 分子量: 332.979
• InChiKey: ADPFMWZEEACOFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(2-bromoethyl)indoline-2,3-dione 在 sodium azide 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 生成 5-bromo-1-[2-[4-[[2-methoxy-4-[(1E,4E)-3-oxo-5-thiophen-2-ylpenta-1,4-dienyl]phenoxy]methyl]triazol-1-yl]ethyl]indole-2,3-dione
  参考文献：
  名称：

  Triazole linked mono carbonyl curcumin-isatin bifunctional hybrids as novel anti tubulin agents: Design, synthesis, biological evaluation and molecular modeling studies

  摘要：

  Keeping in view the limitations associated with currently available anticancer drugs, molecular hybrids of mono carbonyl curcumin and isatin tethered by triazole ring have been synthesized and evaluated for in vitro cytotoxicity against THP-1, COLO-205, HCT-116, A549, HeLa, CAKI-I, PC-3, MiaPaca-2 human cancer cell lines. The results revealed that the compounds SA-1 to SA-9, SB-2, SB-3, SB-4, SB-7 and SC-2 showed a good range of IC50 values against THP-1, COLO-205, HCT-116 and PC-3 cell lines, while the other four cell lines among these were found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and substitution at position R influences the activity. Methoxy substituted phenyl ring as Ring X and H as R were found to be the ideal structural features. The most potent compounds (SA-2, SA-3, SA-4, SA-7) were further tested for tubulin inhibition. Compound SA-2 was found to significantly inhibit the tubulin polymerization (IC50 = 1.2 mu M against HCT-116). Compound SA-2, moreover, lead to the disruption of microtubules as confirmed by immunofluorescence technique. The significant cytotoxicity and tubulin inhibition by SA-2 was streamlined by molecular modeling studies where it was docked at the curcumin binding site of tubulin. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.013
• 作为产物：
  描述：

  5-溴靛红 、 1,2-二溴乙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以62%的产率得到5-bromo-1-(2-bromoethyl)indoline-2,3-dione
  参考文献：
  名称：

  Isatin-1,2,3-三唑-莫西沙星杂种的设计，合成及体外抗分枝杆菌活性

  摘要：

  设计，合成并筛选了新型的Isatin -1,2,3-三唑-莫西沙星（MXFX）杂种5a–j，它们对结核分枝杆菌H 37 Rv和MDR-TB的体外抗分枝杆菌活性。所有合成的杂种（MIC：0.10–0.78μg/ mL）均表现出优异的抗MTB H 37 Rv和MDR-TB活性，尽管它们都不比亲代MXFX（MIC：0.10和0.12μg / mL）更有效。。相对于MTB H 37 Rv，活性最高的5f（MIC：0.10μg / mL）与MXFX相当，且效力比RIF高4倍（MIC：0.39μg/ mL）。针对MDR-TB，所有杂种的活性均高于RIF（MIC：32μg/ mL）和INH（MIC：> 128μg/ mL）。特别是，杂种5e（MIC：0.10μg / mL）与MXFX和256FX相当，且效力比RIF和INH高1,024倍。缀合物5e和5f都需要进一步研究。

  DOI：

  10.1002/jhet.3023

文献信息

• Synthesis and anti-inflammatory activity evaluation of novel triazolyl-isatin hybrids
  作者：Pramod K. Sharma、Sakshi Balwani、Divya Mathur、Shashwat Malhotra、Brajendra K. Singh、Ashok K. Prasad、Christophe Len、Erik V. Van der Eycken、Balaram Ghosh、Nigel G. J. Richards、Virinder S. Parmar

  DOI：10.3109/14756366.2016.1151015

  日期：2016.11.1

  evaluated for their inhibitory activity of TNF-α induced expression of Intercellular Adhesion Molecule-1 (ICAM-1) on the surface of human endothelial cells. Structure-activity relationship (SAR) studies revealed that the presence of the electron-attracting bromo substituent at position-5 of the isatin moiety played an important role in enhancing the anti-inflammatory potential of the synthesized compounds

  合成了新的基于isatin-triazole的杂种，并评估了其在人内皮细胞表面上由TNF-α诱导的细胞间粘附分子1（ICAM-1）表达的抑制活性。结构-活性关系（SAR）研究表明，在靛红部分的5位上存在吸引电子的溴取代基，在增强合成化合物的抗炎潜力中起着重要作用。Z-1- [3-（1H-1,2,4-三唑-1-基）丙基] -5-溴-3- [2-（4-甲氧基苯基）肼基]吲哚-2--2-（19）发现IC50 = 20μM，MTD为200μM时对ICAM-1的抑制率为89％，是所有合成衍生物中最有效的。1,2的介绍
• Design, synthesis and anti-mycobacterial activity evaluation of benzofuran-isatin hybrids
  作者：Feng Gao、Hua Yang、Tianyu Lu、Zijian Chen、Long Ma、Zhi Xu、Paul Schaffer、Guangming Lu

  DOI：10.1016/j.ejmech.2018.09.049

  日期：2018.11

  Herein we report the design and synthesis of a series of novel benzofuran-isatin hybrids, and in vitro evaluation of their anti-mycobacterial activity against both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis (MTB) strains. In parallel, cytotoxicity of these hybrids was also tested in VERO cells. Preliminary results indicated that all hybrids with acceptable cytotoxicity

  本文中，我们报告了一系列新型苯并呋喃-伊斯汀杂种的设计与合成，以及它们对药敏和耐多药（MDR）结核分枝杆菌（MTB）菌株的抗分枝杆菌活性的体外评估。同时，还在VERO细胞中测试了这些杂种的细胞毒性。初步结果表明，在Vero细胞中具有可接受的毒性的所有杂交（CC 50：128-> 1024  μ克/毫升）对MTBħ表现出相当大的抗分枝杆菌活性37 v和MDR-TB与MIC范围为0.25至8  μ克/毫升 值得注意的是，杂种8f对VERO细胞没有细胞毒性（CC 50：> 1024  μ克/毫升）被发现是最活跃的化合物（MIC：0.25和0.5  μ克/毫升）对MTBħ 37 v和MDR-TB的菌株。与一线抗结核药利福平和异烟肼相比，杂种8f对MDR-TB的活性更高。进一步评价了杂合体8f的代谢稳定性和体内药代动力学特征，结果表明，与抑制剂TAM16相比，杂合体8f表现出较低的代谢稳定性。需要基
• Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids
  作者：Renate Hazel Hans、Hong Su、Kelly Chibale

  DOI：10.3762/bjoc.6.78

  日期：——

  A simple and straightforward synthetic approach to potential anti-infective thiolactone-isatin hybrids led to the discovery of novel tetracyclic compounds which bear a macrocylic motif containing an unusual bridged amide bond.

  一种简单直接的合成方法，用于潜在的抗感染硫代内酯-异喹啉杂合物的研究，发现了一种新型四环化合物，其中含有一种罕见的桥接酰胺键的大环基团。
• Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies
  作者：Harbinder Singh、Jatinder V. Singh、Manish K. Gupta、Ajit K. Saxena、Sahil Sharma、Kunal Nepali、Preet Mohinder S. Bedi

  DOI：10.1016/j.bmcl.2017.07.069

  日期：2017.9

  In an attempt to develop potent anti-tubulin agents against most dreadful disease cancer, a library of 28 novel triazole tethered isatin-coumarin hybrids were synthesized by click chemistry approach. Synthesized hybrids were characterized and evaluated against a panel of human cancer cell lines viz. THP-1, COLO-205, HCT-116 and PC-3. Biological assay unveiled that, compounds A-1 to A-6, B-1 to B-4

  为了开发针对大多数可怕疾病癌症的有效抗微管蛋白药物，通过点击化学方法合成了28种新颖的三唑系留的伊斯汀-香豆素杂种的文库。表征合成的杂种并针对一组人类癌细胞系进行评估。THP-1，COLO-205，HCT-116和PC-3。生物测定揭示化合物A-1至A-6，B-1至B-4和C-1至C-3对THP-1，COLO-205和HCT-116细胞系显示出显着的抑制潜力，而THP-1，COLO-205和HCT-116细胞系对设计的杂种更敏感。发现这些细胞系中的PC-3几乎具有抗性。建立的SAR显示出细胞毒性活性对伊斯丁上取代基的类型和与三唑环连接的伊斯丁部分的碳桥长度的显着依赖性。发现未取代的靛红和两个碳桥对于细胞毒性至关重要。进一步测试了三种最有效的杂种（A-1，A-2和B-1）对微管蛋白聚合的抑制作用。在这三种化合物中，IC 50赋予A-1最显着的微管蛋白聚合抑制潜能值1.06 µM，通过共聚焦显
• Design, synthesis and biological evaluation of novel indolinedione–coumarin hybrids as xanthine oxidase inhibitors
  作者：Harmandeep Kaur Gulati、Kavita Bhagat、Atamjit Singh、Nitish Kumar、Arshmeet Kaur、Akriti Sharma、Shilpa Heer、Harbinder Singh、Jatinder Vir Singh、Preet Mohinder S. Bedi

  DOI：10.1007/s00044-020-02589-2

  日期：2020.9

  potent IC50 value against xanthine oxidase enzyme. Kinetic studies were also performed to check the mode of inhibition of most potent compound K-7, which revealed its mixed-type inhibition behavior. Structure-activity relationships revealed that electron-donating groups and small alkyl chains between the two active scaffolds might be beneficial in inhibiting xanthine oxidase enzyme. It was also shown

  合理设计并合成了吲哚啉二酮-香豆素杂合分子文库，以对抗高尿酸血症。通过使用分光光度法测试所有合成的杂合分子，以检查它们对黄嘌呤氧化酶的抑制活性。结果表明，该化合物的IC 50值在6.5-24.5 µM范围内，其中化合物K-7被发现具有最强的抗黄嘌呤氧化酶的IC 50值。还进行了动力学研究，以检查最有效的化合物K-7的抑制方式，揭示了其混合型抑制行为。构效关系揭示了两个活性支架之间的供电子基团和小的烷基链可能对抑制黄嘌呤氧化酶有帮助。还显示出各种静电相互作用将化合物K-7稳定在黄嘌呤氧化酶的活性位点内，这证实了它可以完全阻断其催化活性位点。因此，K-7被认为是有效的黄嘌呤氧化酶抑制剂，可以用作抗高尿酸药物设计的有希望的分子结构单元。