2-(2-溴苯基)-噁唑-4-羧酸乙酯 | 885274-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(2-溴苯基)-噁唑-4-羧酸乙酯
• 中文别名: 2-(2-溴苯基)-4-恶唑羧酸乙酯
• 英文名称: ethyl 2-(2-bromophenyl)-1,3-oxazole-4-carboxylate
• 英文别名: 2-(2-Bromo-phenyl)-oxazole-4-carboxylic acid ethyl ester
• CAS: 885274-67-9
• 化学式: C₁₂H₁₀BrNO₃
• 分子量: 296.12
• InChiKey: JKNMLLKRWOENTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-(2-溴苯基)-噁唑-4-羧酸乙酯 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 2-(2-bromophenyl)-1,3-oxazole-4-carboxylic acid
  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
• 作为产物：
  描述：

  3-溴丙酮酸乙酯 、 2-溴苯甲酰胺 在 silver hexafluoroantimonate 作用下， 以 二氯甲烷 为溶剂， 90.0 ℃ 、500.01 kPa 条件下， 反应 1.0h， 生成 2-(2-溴苯基)-噁唑-4-羧酸乙酯
  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

• Pd-catalyzed desulfitative arylation for the synthesis of 2,5-diarylated oxazole-4-carboxylates using dioxygen as the terminal oxidant
  作者：Xiaodong Tang、Kai Yang、Liying Zeng、Qiang Liu、Huoji Chen

  DOI：10.1039/c7ob01912b

  日期：——

  A novel palladium-catalyzed approach for constructing 2,5-diarylated oxazole-4-carboxylates using sodium arylsulfinates as the aryl source has been demonstrated.

  一种新颖的钯催化方法已被证明可用于利用亚砜酸钠作为芳基来源构建2,5-二芳基氧唑-4-羧酸酯。
• 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.