methyl 3-(benzyloxyamino)propanoate | 30204-31-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 3-(benzyloxyamino)propanoate
• 英文别名: Methyl 3-(phenylmethoxyamino)propanoate
• CAS: 30204-31-0
• 化学式: C₁₁H₁₅NO₃
• 分子量: 209.245
• InChiKey: CYYUEVSSZDHUGF-UHFFFAOYSA-N

物化性质

• 沸点：
  306.9±52.0 °C(Predicted)
• 密度：
  1.098±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(benzyloxyamino)propanoate 在 N-甲基吗啉 、 甲醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 N-{3-[(tert-butoxycarbonyl)amino]propanoyl}-N-hydroxy-β-alanine
  参考文献：
  名称：

  用于 68Ga 核成像的去铁胺 E 铁载体的环状类似物：金黄色葡萄球菌的配位化学和生物活性

  摘要：

  由于耐多药细菌是一个新出现的问题和对人类的威胁，因此积极寻求新的治疗和诊断策略。我们的目标是利用铁载体（由微生物产生的铁特异性强螯合剂）作为镓离子载体进行诊断，应用 Fe(III) 可以成功地被 G​​a(III) 取代而不会失去所研究复合物的生物学特性，这使得分子通过正电子发射断层扫描（PET）成像。在这里，我们报告合成、全溶液化学、热力学表征和去铁胺 E (FOXE) 铁载体的仿生衍生物 (FOX) 的初步生物学评估，用68 Ga 放射性标记可能在金黄色葡萄球菌的 PET 成像中应用. 从一系列六种仿生类似物（与 FOXE 的循环长度和异羟肟酸和酰胺基团的位置不同）中，确定了大多数 FOXE 类似化合物 - FOX 2-4 和 FOX 的最高 Fe(III) 和 Ga(III) 稳定性2-5; 我们还建立了 Ga-FOXE 复合物的稳定常数。为此，使用了光谱和电位滴定以及 Fe(III)-Ga(III)

  DOI：

  10.1021/acs.inorgchem.1c02453
• 作为产物：
  描述：

  O-苄基羟胺 在 盐酸 、 camphor-10-sulfonic acid 、 sodium cyanoborohydride 作用下， 以 乙醇 、 水 、 xylene 为溶剂， 反应 36.0h， 生成 methyl 3-(benzyloxyamino)propanoate
  参考文献：
  名称：

  一种不寻常的氧化环化作用：对仿生大黄素合成的研究。

  摘要：

  N-羟基吡啶酮9与Z-2-环癸烯酮11的异常氧化环化反应已实现，从而证明了可能的仿生途径可生成吡啶酮crolidin 2。

  DOI：

  10.1021/ol034736n

文献信息

• 4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of the JumonjiC-Domain-Containing Histone Demethylase KDM4A
  作者：Ludovica Morera、Martin Roatsch、Michael C. D. Fürst、Inga Hoffmann、Johanna Senger、Mirjam Hau、Henriette Franz、Roland Schüle、Markus R. Heinrich、Manfred Jung

  DOI：10.1002/cmdc.201600218

  日期：2016.9.20

  Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate-based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50 value of 25.4 μm. Herein we report the synthesis and biochemical evaluations

  调节H3K9和H3K36甲基化状态的组蛋白赖氨酸脱甲基酶KDM4A的过表达与几种人类癌症的病理学有关。我们发现以前报道的基于异羟肟酸酯的组蛋白脱乙酰基酶（HDAC）抑制剂（SW55）也能够以25.4μm的IC50值弱抑制这种脱甲基酶。在这里，我们报告了该铅结构的一系列衍生物的合成和生化评估，以及两个正交的体外测定。通过对前导结构进行广泛的化学修饰，还通过利用芳基重氮盐进行自由基芳基化的多功能性，我们能够将衍生物对KDM4A的效力提高至低微摩尔范围，更重要的是，获得了对KDM4A的脱甲基酶选择性。对HDAC的尊重。
• Studies towards the biomimetic synthesis of pyridomacrolidin
  作者：Nageswara Rao Irlapati、Jack E. Baldwin、Robert M. Adlington、Gareth J. Pritchard、Andrew R. Cowley

  DOI：10.1016/j.tet.2006.01.090

  日期：2006.5

  A possible biomimetic synthesis of pyridomacrolidin has been proposed and experimentally supported by carrying out a model study. Regio and stereospecific [3+2] cycloaddition of an in situ generated unusual di-tert-butylated acyl nitrone with Z-2-cyclodecenone and subsequent aromatisation was the key step in our proposed biomimetic synthesis. Finally a pyridomacrolidin analogue was prepared via Friedel–Crafts

  已经提出了可能的仿生大黄素合成方法，并通过进行模型研究得到了实验支持。原位生成的不寻常的二叔丁基化酰基硝酮与Z -2-环癸烯酮的区域和立体特异性[3 + 2]环加成反应以及随后的芳构化是我们拟议的仿生合成的关键步骤。最后，通过环加合物的Friedel-Crafts二脱叔丁基化反应制备了一个嘧啶大环素类似物。
• Synthesis of linear and cyclic trihydroxamic acids as models for ferrioxamines E and G
  作者：Kazuyuki Shimizu、Masayasu Akiyama

  DOI：10.1039/c39850000183

  日期：——

  Linear and cyclic trihydroxamic acids including the 6-aminohexanoyl-3-(hydroxyamino)propanoyl sequence have been synthesized in a stepwise manner from the appropriately protected acyl derivatives and used as iron(III) chelating compounds.

  包含6-氨基己酰基-3-（羟基氨基）丙酰基序列的直链和环状三氧肟酸已由适当保护的酰基衍生物以逐步方式合成，并用作铁（III）螯合化合物。
• Identification of Jumonji AT-Rich Interactive Domain 1A Inhibitors and Their Effect on Cancer Cells
  作者：Yukihiro Itoh、Hideyuki Sawada、Miki Suzuki、Toshifumi Tojo、Ryuzo Sasaki、Makoto Hasegawa、Tamio Mizukami、Takayoshi Suzuki

  DOI：10.1021/acsmedchemlett.5b00083

  日期：2015.6.11

  Jumonji AT-rich interactive domain IA (JARID1A), one of the jumonji C domain-containing histone demethylase (JHDM) family members, plays key roles in cancer cell proliferation and development of drug tolerance. Therefore, selective JARIDIA inhibitors are potential anticancer agents. In this study, we searched for cell-active JARID1A inhibitors by screening hydroxamate compounds in our in-house library and the structural optimization based on docking study of the hit-compound to a homology model of JARID1A. As a result, we identified compound 6j, which selectively inhibits JARID1A over three other JHDM family members. Compound 7j, a prodrug form of compound 6j, induced a selective increase in the level of trimethylation of histone H3 lysine 4, a substrate of JARID1A. Furthermore, compound 7j synergistically enhanced A549 human lung cancer cell growth inhibition induced by vorinostat, a histone deacetylase inhibitor. These findings support the idea that JARIDIA inhibitors have potential as anticancer agents.
• Design, Synthesis, Enzyme-Inhibitory Activity, and Effect on Human Cancer Cells of a Novel Series of Jumonji Domain-Containing Protein 2 Histone Demethylase Inhibitors
  作者：Shohei Hamada、Takayoshi Suzuki、Koshiki Mino、Koichi Koseki、Felix Oehme、Ingo Flamme、Hiroki Ozasa、Yukihiro Itoh、Daisuke Ogasawara、Haruka Komaarashi、Aiko Kato、Hiroki Tsumoto、Hidehiko Nakagawa、Makoto Hasegawa、Ryuzo Sasaki、Tamio Mizukami、Naoki Miyata

  DOI：10.1021/jm1003655

  日期：2010.8.12

  Selective inhibitors of Jumonji domain-containing protein (JMJD) histone demethylases are candidate anticancer agents as well as potential tools for elucidating the biological functions of JMJDs. On the basis of the crystal structure of JMJD2A and a homology model of JMJD2C, we designed and prepared a series of hydroxamate analogues bearing a tertiary amine. Enzyme assays using JMJD2C, JMJD2A, and prolyl hydroxylases revealed that hydroxamate analogue 8 is a potent and selective JMJD2 inhibitor, showing 500-fold greater JMJD2C-inhibitory activity and more than 9100-fold greater JMJD2C-selectivity compared with the lead compound N-oxalylglycine 2. Compounds 17 and 18, prodrugs of compound 8, each showed synergistic growth inhibition of cancer cells in combination with an inhibitor of lysine-specific demethylase I (LSD1). These findings suggest that combination treatment with JMJD2 inhibitors and LSD I inhibitors may represent a novel strategy for anticancer chemotherapy.