N-(3-bromophenyl)-2-hydroxyiminacetamide | 65971-74-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-bromophenyl)-2-hydroxyiminacetamide
• 英文别名: N-(3-bromophenyl)-2-(hydroxyimino)ethanamide；N-(3-bromo-phenyl)-2-hydroxyimino-acetamide；Acetamide, N-(3-bromophenyl)-2-(hydroxyimino)-；N-(3-bromophenyl)-2-hydroxyiminoacetamide
• CAS: 65971-74-6
• 化学式: C₈H₇BrN₂O₂
• mdl: MFCD00462281
• 分子量: 243.06
• InChiKey: ORVVNXAFZBVFMP-UHFFFAOYSA-N

物化性质

• 熔点：
  165 °C
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-bromophenyl)-2-hydroxyiminacetamide 在 硫酸 、 sodium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 5.25h， 生成 1-甲基-6-溴靛玉红
  参考文献：
  名称：

  Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases

  摘要：

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.

  DOI：

  10.1021/jm031016d
• 作为产物：
  描述：

  水合氯醛 、 间溴苯胺 在 盐酸 、 盐酸羟胺 、 sodium sulfate 作用下， 以 水 为溶剂， 反应 2.08h， 生成 N-(3-bromophenyl)-2-hydroxyiminacetamide
  参考文献：
  名称：

  多取代靛红衍生物的合成及抗增殖活性评价

  摘要：

  利用强大的桑德迈尔反应合成了一系列多取代靛红衍生物。这些衍生物的结构均通过1H-NMR、13C-NMR和HR-MS证实。使用MTT测定体外评估这些衍生物对人白血病细胞(K562)、人肝细胞癌细胞(HepG2)和人结肠癌细胞(HT-29)增殖活性的抑制作用。其中，化合物4l对K562、HepG2和HT-29细胞表现出较强的抗增殖活性，IC50值分别为1.75、3.20和4.17 μM。随后评价化合物4l在K562细胞中的形态学、生长抑制和凋亡作用、在HepG2细胞中的伤口愈合作用以及在HUVEC细胞的基质凝胶中的管形成作用。所有结果表明化合物4l可以作为进一步研究中潜在的抗肿瘤剂。

  DOI：

  10.3390/molecules26010176

文献信息

• Counter-Current chromatography separation of isatin derivatives using the sandmeyer methodology
  作者：Márcia R. Almeida、Gilda G. Leitão、Bárbara V. Silva、Jussara P. Barbosa、Angelo C. Pinto

  DOI：10.1590/s0103-50532010000400025

  日期：——

  method, using high-speed counter-current chromatography (HSCCC) technique, was developed for the separation of isomeric isatin derivatives, prepared following the Sandmeyer route. The biphasic solvent system composed of hexane:ethyl acetate:ethanol:water 1:0.5:0.5:1 (v/v/v/v) was used for all separations.

  开发了一种快速高效的方法，使用高速逆流色谱（HSCCC）技术分离按照Sandmeyer路线制备的同分异构的Isatin衍生物。所有分离均使用由己烷：乙酸乙酯：乙醇：水1：0.5：0.5：1（v / v / v / v）组成的双相溶剂系统。
• A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters
  作者：Yong-Yuan Gui、Jian Yang、Liang-Wen Qi、Xiao Wang、Fang Tian、Xiao-Nian Li、Lin Peng、Li-Xin Wang

  DOI：10.1039/c5ob00774g

  日期：——

  Enantioselective sulfa-Michael/aldol reaction of isoindigos has been successfully developed to afford bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters.

  对isoindigos进行的对映选择性磺酰-Michael/aldol反应已成功开发，以获得具有邻位季铵螺环中心的双螺环氧吲哚四氢噻吩。
• Isatin <i>N</i>,<i>N</i>′-Cyclic Azomethine Imine 1,3-Dipole and Abnormal [3 + 2]-Cycloaddition with Maleimide in the Presence of 1,4-Diazabicyclo[2.2.2]octane
  作者：Xiao Wang、Peng Yang、Yong Zhang、Chao-Zhe Tang、Fang Tian、Lin Peng、Li-Xin Wang

  DOI：10.1021/acs.orglett.6b03815

  日期：2017.2.3

  A new isatin N,N′-cyclic azomethine imine synthon was devised, and an unexpected abnormal [3 + 2]-cycloaddition with maleimide catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) has been disclosed. A variety of tricyclic spiropyrrolidine oxindoles bearing a dinitrogen heterocycle and succinimide scaffold were obtained in excellent yields (up to 96%) and diastereoselectivities (up to 97:3) under mild

  设计了一种新的Isatin N，N'-环甲亚胺亚胺合子，并公开了1,4-二氮杂双环[2.2.2]辛烷（DABCO）催化的马来酰亚胺意外异常[3 + 2]-环加成反应。在温和条件下，以优异的收率（高达96％）和非对映选择性（高达97：3）获得了多种带有二氮杂环和琥珀酰亚胺支架的三环螺吡咯烷恶唑。
• Substituted Amino-Pyrimidine Derivatives
  申请人：Endo Pharmaceuticals Inc.

  公开号：US20140038952A1

  公开（公告）日：2014-02-06

  The present application provides novel substituted quinazoline and pyrido-pyrimidine compounds and pharmaceutically acceptable salts, prodrugs, and solvates thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating PI3K and/or mTOR activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the PI3K/AKT/mTOR pathway. Advantageously, these compounds perform as dual PI3K/mTOR inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

  本申请提供了新型的取代喹唑啉和吡啶并嘧啶化合物及其药用可接受的盐、前药和溶剂化合物。还提供了制备这些化合物的方法。通过向患者投予一种或多种化合物的治疗有效量，这些化合物在共同调节PI3K和/或mTOR活性方面是有用的。通过这样做，这些化合物在治疗与PI3K/AKT/mTOR途径失调相关的疾病方面是有效的。有利的是，这些化合物作为双重PI3K/mTOR抑制剂发挥作用。可以使用这些化合物治疗各种疾病，包括以炎症或异常细胞增殖为特征的疾病。在一个实施例中，该疾病是癌症。
• Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4
  作者：Mui Cheung、Weike Bao、David J. Behm、Carl A. Brooks、Michael J. Bury、Sarah E. Dowdell、Hilary S. Eidam、Ryan M. Fox、Krista B. Goodman、Dennis A. Holt、Dennis Lee、Theresa J. Roethke、Robert N. Willette、Xiaoping Xu、Guosen Ye、Kevin S. Thorneloe

  DOI：10.1021/acsmedchemlett.7b00094

  日期：2017.5.11

  failure. Herein we report the discovery of an orally active, potent, and selective TRPV4 blocker, 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK2193874, 28) after addressing an unexpected off-target cardiovascular liability observed from in vivo studies. GSK2193874 is a selective tool for elucidating TRPV4 biology both in vitro

  瞬时受体电位Vanilloid 4（TRPV4）是阳离子通道的瞬时受体电位（TRP）超家族的成员。TRPV4在肺部的血管内皮中表达，并调节肺泡间隔屏障的完整性。升高的肺血管压力会引起TRPV4依赖性肺水肿，因此，抑制TRPV4代表了一种新的方法来治疗与充血性心力衰竭等疾病相关的肺水肿。在这里，我们报告发现了口服活性，有效和选择性TRPV4阻滞剂3-（1,4'-bipiperidin-1'-ylmethyl）-7-bromo-N-（1-苯基环丙基）-2- [3- （三氟甲基）苯基] -4-喹啉羧酰胺（GSK2193874，28）解决了从体内研究中观察到的意外脱靶心血管不良反应。