2-(2-bromophenyl)-1,3-oxazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-bromophenyl)-1,3-oxazole-4-carboxylic acid
• 化学式: C₁₀H₆BrNO₃
• 分子量: 268.067
• InChiKey: BENPEZKVSIFIEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-bromophenyl)-1,3-oxazole-4-carboxylic acid 在 N-甲基吗啉 、 氯甲酸乙酯 、 盐酸羟胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.67h， 以3%的产率得到2-(2-bromophenyl)-1,3-oxazole-4-carbohydroxamic 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：

  2-溴苯甲酰胺 在 silver hexafluoroantimonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 20.0~90.0 ℃ 、500.01 kPa 条件下， 反应 5.0h， 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