6-溴-5-甲氧基吲哚-2,3-二酮 | 130420-78-9

• 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: 6-溴-5-甲氧基吲哚-2,3-二酮
• 英文名称: 6-bromo-5-methoxy-indoline-2,3-dione
• 英文别名: 5-methoxy-6-bromo-isatin；6-bromo-5-methoxyisatin；6-broMo-5-Methoxyindoline-2,3-dione；6-bromo-5-methoxy-1H-indole-2,3-dione
• CAS: 130420-78-9
• 化学式: C₉H₆BrNO₃
• 分子量: 256.056
• InChiKey: YAPKYMNANRNKHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二氯苯基锑 、 6-溴-5-甲氧基吲哚-2,3-二酮 在 三乙胺 作用下， 以 甲醇 为溶剂， 以78%的产率得到phenylantimony(III) bis(5-methoxy-6-bromoisatin)
  参考文献：
  名称：

  Singhal, Kiran, Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 1993, vol. 23, p. 1363 - 1378

  摘要：

  DOI：
• 作为产物：
  描述：

  3-溴-4-甲氧基苯胺 在 硫酸 、 盐酸羟胺 、 sodium sulfate 作用下， 以 水 为溶剂， 反应 0.2h， 生成 6-溴-5-甲氧基吲哚-2,3-二酮
  参考文献：
  名称：

  Varma; Singh, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 6, p. 578 - 581

  摘要：

  DOI：

文献信息

• Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones
  作者：Stephen E. Webber、Ted M. Bleckman、John Attard、Judith G. Deal、Vinit Kathardekar、Katherine M. Welsh、Stephanie Webber、Cheryl A. Janson、David A. Matthews

  DOI：10.1021/jm00058a010

  日期：1993.3

  The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-resolution ternary crystal complex of Escherichia coli TS, 5'-fluorodeoxyuridylate (5-FdUMP)

  描述了新型胸苷酸合酶（TS）抑制剂的设计，合成和生物学评估。通过对蛋白质-配体结构的重复晶体学分析来进行分子设计。在该项目开始时，我们专注于大肠杆菌TS，5'-氟脱氧尿酸（5-FdUMP）和经典的含谷氨酸叶酸类似物的高分辨率三元晶体复合物的叶酸辅因子结合位点。一种新型化合物的初步三元晶体结构已成功解决。通过分析该初始复合物，进行了进一步的结构修饰，并开发了一系列活性5-（芳硫基）喹唑啉酮。合成策略基于各种芳基硫代阴离子置换喹唑啉酮5位上的卤素。测试化合物对纯化的大肠杆菌和/或人TS的抑制作用，并在体外测定针对三种肿瘤细胞系的细胞毒性。用几种抑制剂观察到了重要的胸腺嘧啶核苷保护作用，表明TS是细胞内活性位点。
• Utilizing Solubility Differences to Achieve Regiocontrol in the Synthesis of Substituted Quinoline-4-carboxylic Acids
  作者：Peter Lindsay-Scott、Helen Barlow

  DOI：10.1055/s-0035-1561395

  日期：——

  A practical method for the regiocontrolled synthesis of substituted quinoline-4-carboxylic acids is described. Solubility differences between the product quinoline regioisomers enable their facile separation, thus avoiding any challenging chromatographic purifications and allowing access to highly substituted quinoline compounds in three steps from commercially available anilines.

  描述了一种用于区域控制合成取代喹啉-4-羧酸的实用方法。产品喹啉区域异构体之间的溶解度差异使其易于分离，从而避免了任何具有挑战性的色谱纯化，并允许通过三个步骤从市售苯胺中获得高度取代的喹啉化合物。
• [EN] ANTIPROLIFERATIVE QUINAZOLINES<br/>[FR] QUINAZOLINES ANTI-PROLIFERATIVES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1993020055A1

  公开（公告）日：1993-10-14

  (EN) Quinazoline compounds which demonstrate antiproliferative activity, such as antitumor activity, processes of preparing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds. These compounds inhibit the growth and proliferation of the cells of higher organisms and microorganisms, such as bacteria, yeasts and fungi. Preferred quinazoline compounds are capable of inhibiting the enzyme thymidylate synthase. Effects derived from the inhibition of the enzyme thymidylate synthase include those discussed above.(FR) On décrit des composés de quinazoline qui manifestent une activité anti-proliférative telle qu'une activité anti-tumorale, des procédés permettant de préparer ces composés, des compositions pharmaceutiques qui les contiennent, ainsi que l'utilisation desdits composés. Ces derniers inhibent la croissance et la prolifération de cellules chez les organismes supérieurs et les micro-organismes tels que les bactéries, les levures et les champignons. Des composés de quinazoline préférés sont en mesure d'inhiber une enzyme, la thymidylate synthase. Les effets provenant de cette inhibition de la thymidylate synthase incluent ceux mentionnés ci-dessus.

  (中) 描述了一种表现出抗增殖活性，如抗肿瘤活性的喹唑啉化合物，以及制备这些化合物的过程，含有这些化合物的药物组合物，以及这些化合物的用途。这些化合物抑制高等生物和微生物（如细菌，酵母菌和真菌）的细胞生长和增殖。优选的喹唑啉化合物能够抑制胸腺嘧啶合成酶酶。由抑制胸腺嘧啶合成酶酶产生的效应包括上述讨论的效应。
• Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay
  作者：Nilantha Sirisoma、Azra Pervin、John Drewe、Ben Tseng、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2009.03.121

  日期：2009.5

  We report the discovery of a series of substituted N'-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N'-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC50 value of 0.24 mu M in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N'-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.056 mu M in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC50 values of 0.17, 0.088 and 0.14 mu M in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization. (C) 2009 Elsevier Ltd. All rights reserved.
• Rastogi, Nisheeth; Sethi, Rakesh; Varma, Rajendra Singh, Journal of the Indian Chemical Society, 2008, vol. 85, # 5, p. 513 - 516
  作者：Rastogi, Nisheeth、Sethi, Rakesh、Varma, Rajendra Singh、Tripathi, Diwakar

  DOI：——

  日期：——