ethyl (2Z)-2-benzamido-2-hydroxyiminoacetate

• 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: ethyl (2Z)-2-benzamido-2-hydroxyiminoacetate
• 化学式: C₁₁H₁₂N₂O₄
• 分子量: 236.227
• InChiKey: BQNIDNRWOVMFLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (2Z)-2-benzamido-2-hydroxyiminoacetate 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以60%的产率得到5-苯基-1,2,4-噁二唑-3-羧酸乙酯
  参考文献：
  名称：

  Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis

  摘要：

  In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 mu M) with no obvious cytotoxicity (CC50 > 50 mu M). It effectively attenuated hypoxia-induced HIF-1 alpha protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.

  DOI：

  10.1021/acs.jmedchem.9b01313
• 作为产物：
  描述：

  苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 ethyl (2Z)-2-benzamido-2-hydroxyiminoacetate
  参考文献：
  名称：

  Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors

  摘要：

  Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several nonhistone proteins. Here we report the preparation of thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic procedure. We identified them as selective HDAC6 inhibitors by investigating the inhibition of B recombinant HDAC enzymes and the protein acetylation in cells by Western blotting (tubulin vs histone acetylation). The most active compounds exhibited nanomolar potency and high selectivity for HDAC6. For example, an oxazole hydroxamate inhibits HDAC6 with an IC50 of 59 nM and has a selectivity index of >200 against HDAC1 and HDAC8. This is the first report showing that the nature of a heterocycle directly connected to a zinc binding group (ZBG) can be used to modulate subtype selectivity and potency for HDAC6 inhibitors to such an extent. We rationalize the high potency and selectivity of the oxazoles by molecular modeling and docking.

  DOI：

  10.1021/acs.jmedchem.5b01493

文献信息

• Strani,G.; Garau,A.M., Gazzetta Chimica Italiana, 1963, vol. 93, p. 482 - 492
  作者：Strani,G.、Garau,A.M.

  DOI：——

  日期：——
• Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors
  作者：Johanna Senger、Jelena Melesina、Martin Marek、Christophe Romier、Ina Oehme、Olaf Witt、Wolfgang Sippl、Manfred Jung

  DOI：10.1021/acs.jmedchem.5b01493

  日期：2016.2.25

  Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several nonhistone proteins. Here we report the preparation of thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic procedure. We identified them as selective HDAC6 inhibitors by investigating the inhibition of B recombinant HDAC enzymes and the protein acetylation in cells by Western blotting (tubulin vs histone acetylation). The most active compounds exhibited nanomolar potency and high selectivity for HDAC6. For example, an oxazole hydroxamate inhibits HDAC6 with an IC50 of 59 nM and has a selectivity index of >200 against HDAC1 and HDAC8. This is the first report showing that the nature of a heterocycle directly connected to a zinc binding group (ZBG) can be used to modulate subtype selectivity and potency for HDAC6 inhibitors to such an extent. We rationalize the high potency and selectivity of the oxazoles by molecular modeling and docking.
• Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
  作者：Mingming Liu、Yuru Liang、Zhongzhen Zhu、Jin Wang、Xingxing Cheng、Jiayi Cheng、Binpeng Xu、Rong Li、Xinhua Liu、Yang Wang

  DOI：10.1021/acs.jmedchem.9b01313

  日期：2019.10.24

  In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 mu M) with no obvious cytotoxicity (CC50 > 50 mu M). It effectively attenuated hypoxia-induced HIF-1 alpha protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.