2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid | 56401-28-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid
• 英文别名: 4-Hydroxyphenylpyruvic acid oxime；2-hydroxyimino-3-(4-hydroxyphenyl)propanoic acid
• CAS: 56401-28-6
• 化学式: C₉H₉NO₄
• 分子量: 195.175
• InChiKey: HOSMGQOSNROJPE-UHFFFAOYSA-N

物化性质

• 熔点：
  168-169 °C
• 沸点：
  489.1±47.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  90.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid 在 硫酸 、 溶剂黄146 作用下， 生成 对羟基苯乙酸
  参考文献：
  名称：

  Cornforth, Chemistry of Penicillin

  摘要：

  DOI：
• 作为产物：
  描述：

  2-hydroxy-3-(4-hydroxyphenyl)acrylic acid 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 12.0h， 以91%的产率得到2-(hydroxyimino)-3-(4-hydroxyphenyl)propanoic acid
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)

  摘要：

  C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 mu M). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 mu M) and 3-chloro- (IC50 = 0.17 mu M) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.04.037

文献信息

• SYNTHESE DES ACIDES AMINES A PARTIR DE LA RHODANINE
  作者：Roger Gaudry、Robert A. Mcivor

  DOI：10.1139/v51-051

  日期：1951.6.1

  The Gränacher method has been investigated to discover its applicability to the synthesis of a variety of natural amino acids. The procedure has been simplified for phenylalanine and tyrosine, and extended to valine and isoleucine. An unusual product of the oximation of α-thioketo-β-(p-methoxyphenyl)propionic acid is described.

  Gränacher方法已被研究，以发现其在合成各种天然氨基酸中的适用性。该程序已经简化用于苯丙氨酸和酪氨酸，并扩展到缬氨酸和异亮氨酸。描述了α-硫代酮基-β-(对甲氧基苯基)丙酸的羟肟化反应的异常产物。
• Camptothecin-psammaplin A hybrids as topoisomerase I and HDAC dual-action inhibitors
  作者：Raffaella Cincinelli、Loana Musso、Roberto Artali、Mario Guglielmi、Erminia Bianchino、Francesco Cardile、Fabiana Colelli、Claudio Pisano、Sabrina Dallavalle

  DOI：10.1016/j.ejmech.2017.11.021

  日期：2018.1

  compound, we designed new dual-acting multivalent molecules simultaneously targeting topoisomerase I and HDAC. In particular, a selected compound containing a camptothecin and the psammaplin A scaffold showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473

  最近的研究表明，由喜树碱衍生物和HDAC抑制剂组成的联合疗法具有增强的抗癌作用。为了在单一活性化合物中发挥这种协同作用，我们设计了同时靶向拓扑异构酶I和HDAC的新型双作用多价分子。特别地，包含喜树碱和psaMMaplin A支架的所选化合物显示出广谱的抗增殖活性，IC 50值在纳摩尔范围内。初步的体内结果表明对CD-1裸鼠原位异种移植的人间皮瘤原代细胞MM473有很强的抗肿瘤活性，并且具有很高的耐受性。
• Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects
  作者：Véronique Mathieu、Nathalie Wauthoz、Florence Lefranc、Hendrik Niemann、Karim Amighi、Robert Kiss、Peter Proksch

  DOI：10.3390/molecules18033543

  日期：——

  Bastadins-6, -9 and -16 isolated from the marine sponge Ianthella basta displayed in vitro cytostatic and/or cytotoxic effects in six human and mouse cancer cell lines. The in vitro growth inhibitory effects of these bastadins were similar in cancer cell lines sensitive to pro-apoptotic stimuli versus cancer cell lines displaying various levels of resistance to pro-apoptotic stimuli. While about ten times less toxic than the natural cyclic bastadins, the synthetically derived 5,5'-dibromohemibastadin-1 (DBHB) displayed not only in vitro growth inhibitory activity in cancer cells but also anti-angiogenic properties. At a concentration of one tenth of its in vitro growth inhibitory concentration, DBHB displayed actual antimigratory effects in mouse B16F10 melanoma cells without any sign of cytotoxicity and/or growth inhibition. The serum concentration used in the cell culture media markedly influenced the DBHB-induced antimigratory effects in the B16F10 melanoma cell population. We are currently developing a specific inhalation formulation for DBHB enabling this compound to avoid plasmatic albumin binding through its direct delivery to the lungs to combat primary as well as secondary (metastases) tumors.

  从海洋海绵 Ianthella basta 中分离出的 Bastadins-6、-9 和 -16 对六种人类和小鼠癌细胞株具有体外细胞抑制和/或细胞毒性作用。在对促凋亡刺激敏感的癌细胞系和对促凋亡刺激有不同程度抵抗力的癌细胞系中，这些韧皮部蛋白的体外生长抑制作用相似。合成的 5,5'-二溴半胱氨酸-1（DBHB）的毒性比天然环状韧皮部素低十倍左右，它不仅具有体外抑制癌细胞生长的活性，还具有抗血管生成的特性。当浓度为体外生长抑制浓度的十分之一时，DBHB 在小鼠 B16F10 黑色素瘤细胞中显示出实际的抗移行作用，而没有任何细胞毒性和/或生长抑制的迹象。细胞培养基中使用的血清浓度明显影响 DBHB 在 B16F10 黑色素瘤细胞群中诱导的抗移行效应。我们目前正在开发 DBHB 的特殊吸入配方，使这种化合物能够通过直接输送到肺部来避免血浆白蛋白的结合，从而对抗原发性和继发性（转移）肿瘤。
• Complementary mechanochemical and biphasic approaches for the synthesis of organic thiocyanates using hexacyanoferrates as non-toxic cyanide sources
  作者：Caroline Grundke、Jonathan Groß、Nina Vierengel、Jason Sirleaf、Matthias Schmitz、Leonie Krieger、Till Opatz

  DOI：10.1039/d2ob02216h

  日期：——

  starting from commercially available thiols or disulfides. Additionally, the application of this mild method to the first total synthesis of psammaplin B is demonstrated. Non-toxic and inexpensive ferricyanide is used as the cyanide source, which can be activated either in a mechanochemical, solvent-free approach, or in a biphasic solvent system allowing easier work-up. A total of 27 examples is demonstrated

  在此，我们描述了两种互补的方法来制备各种有机硫氰酸盐，这些有机硫氰酸盐价格低廉、可靠并遵循可持续化学的原则，从市售的硫醇或二硫化物开始。此外，还展示了这种温和方法在 psammaplin B 的首次全合成中的应用。氰化物源使用无毒且廉价的铁氰化物，可以通过机械化学、无溶剂方法或双相溶剂系统激活，从而更容易进行后处理。总共展示了 27 个示例，具有高达定量的产量。
• Yoder et al., Proceedings of the Iowa Academy of Science, 1954, vol. 61, p. 271,275
  作者：Yoder et al.

  DOI：——

  日期：——