2,6-dibromo-4-((2-methyl-5-oxooxazol-4(5H)-ylidene)methyl)phenyl acetate | 91805-72-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2,6-dibromo-4-((2-methyl-5-oxooxazol-4(5H)-ylidene)methyl)phenyl acetate
• 英文别名: 4-(4-acetoxy-3,5-dibromo-benzylidene)-2-methyl-4H-oxazol-5-one；4-<4-Acetoxy-3.5-dibrom-benzyliden>-2-methyl-oxazolon-(5)
• CAS: 91805-72-0
• 化学式: C₁₃H₉Br₂NO₄
• 分子量: 403.027
• InChiKey: ATTYNWAOFPKABN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.96
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2,6-dibromo-4-((2-methyl-5-oxooxazol-4(5H)-ylidene)methyl)phenyl acetate 在 吡啶 、 盐酸 、 水 作用下， 生成
  参考文献：
  名称：

  Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A against Its Epigenetic Targets

  摘要：

  Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotcodcity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.

  DOI：

  10.1021/jm2016182
• 作为产物：
  描述：

  3,5-二溴-4-羟基苯甲醛 、 乙酸酐 、 N-乙酰甘氨酸 在 sodium acetate 作用下， 以56%的产率得到2,6-dibromo-4-((2-methyl-5-oxooxazol-4(5H)-ylidene)methyl)phenyl acetate
  参考文献：
  名称：

  Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A against Its Epigenetic Targets

  摘要：

  Psammaplin A (11c) is a marine metabolite previously reported to be a potent inhibitor of two classes of epigenetic enzymes: histone deacetylases and DNA methyltransferases. The design and synthesis of a focused library based on the psammaplin A core has been carried out to probe the molecular features of this molecule responsible for its activity. By direct in vitro assay of the free thiol generated upon reduction of the dimeric psammaplin scaffold, we have unambiguously demonstrated that 11c functions as a natural prodrug, with the reduced form being highly potent against HDAC1 in vitro (IC50 0.9 nM). Furthermore, we have shown it to have high isoform selectivity, being 360-fold selective for HDAC1 over HDAC6 and more than 1000-fold less potent against HDAC7 and HDAC8. SAR around our focused library revealed a number of features, most notably the oxime functionality to be important to this selectivity. Many of the compounds show significant cytotoxicity in A549, MCF7, and W138 cells, with the SAR of cytotcodcity correlating to HDAC inhibition. Furthermore, compound treatment causes upregulation of histone acetylation but little effect on tubulin acetylation. Finally, we have found no evidence for 11c functioning as a DNMT inhibitor.

  DOI：

  10.1021/jm2016182

文献信息

• Model Reactions for the Biosynthesis of Thyroxine. VIII. The Reaction of Various Analogs of 4-Hydroxy-3,5-diiodophenylpyruvic Acid with 3,5-Diiodotyrosine^1,2
  作者：Tetsuo Shiba、H. J. Cahnmann、Teruo Matsuura、Akira Nishinaga、Harushige Sakamoto

  DOI：10.1021/jo01033a501

  日期：1964.10