8-bromo-6-chloro-4-oxo-2-phenethyl-4H-chromene-3-carbonitrile | 1224712-18-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-bromo-6-chloro-4-oxo-2-phenethyl-4H-chromene-3-carbonitrile
• 英文别名: 8-Bromo-6-chloro-4-oxo-2-(2-phenylethyl)chromene-3-carbonitrile
• CAS: 1224712-18-8
• 化学式: C₁₈H₁₁BrClNO₂
• 分子量: 388.648
• InChiKey: PXRQTMCDSNNQCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-bromo-6-chloro-4-oxo-2-phenethyl-4H-chromene-3-carbonitrile 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 以66%的产率得到(Z)-3-(aminomethylene)-8-bromo-6-chloro-(2-phenethyl)choman-4-one
  参考文献：
  名称：

  Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells

  摘要：

  Sirtuins (SIRTs) catalyze the NAD(+)-dependent deacetylation of N-e-acetyl lysines on various protein substrates. SIRTs are interesting drug targets as they are considered to be related to important pathologies such as inflammation and aging-associated diseases. We have previously shown that chroman-4-ones act as potent and selective inhibitors of SIRT2. Herein we report novel chroman-4-one and chromone-based SIRT2 inhibitors containing various heterofunctionalities to improve pharmacokinetic properties. The compounds retained both high SIRT2 selectivity and potent inhibitory activity. Two compounds were tested for their antiproliferative effects in breast cancer (MCF-7) and lung carcinoma (A549) cell lines. Both compounds showed antiproliferative effects correlating with their SIRT2 inhibition potency. They also increased the acetylation level of a-tubulin, indicating that SIRT2 is likely to be the target in cancer cells. A binding mode of the inhibitors that is consistent with the SAR data was proposed based on a homology model of SIRT2.

  DOI：

  10.1021/jm500930h
• 作为产物：
  描述：

  在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 8-bromo-6-chloro-4-oxo-2-phenethyl-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells

  摘要：

  Sirtuins (SIRTs) catalyze the NAD(+)-dependent deacetylation of N-e-acetyl lysines on various protein substrates. SIRTs are interesting drug targets as they are considered to be related to important pathologies such as inflammation and aging-associated diseases. We have previously shown that chroman-4-ones act as potent and selective inhibitors of SIRT2. Herein we report novel chroman-4-one and chromone-based SIRT2 inhibitors containing various heterofunctionalities to improve pharmacokinetic properties. The compounds retained both high SIRT2 selectivity and potent inhibitory activity. Two compounds were tested for their antiproliferative effects in breast cancer (MCF-7) and lung carcinoma (A549) cell lines. Both compounds showed antiproliferative effects correlating with their SIRT2 inhibition potency. They also increased the acetylation level of a-tubulin, indicating that SIRT2 is likely to be the target in cancer cells. A binding mode of the inhibitors that is consistent with the SAR data was proposed based on a homology model of SIRT2.

  DOI：

  10.1021/jm500930h

文献信息

• KHMDS Enhanced SmI₂-Mediated Reformatsky Type α-Cyanation
  作者：Tobias Ankner、Maria Fridén-Saxin、Nils Pemberton、Tina Seifert、Morten Grøtli、Kristina Luthman、Göran Hilmersson

  DOI：10.1021/ol100424y

  日期：2010.5.21

  A novel combination of SmI2, KHMDS, and TsCN can be utilized to introduce a cyano group into structurally diverse and highly sensitive 2-alkyl-chroman-4-ones. Subsequent oxidation allows the formed 2-alkyl-3-cyanochromones to be isolated in yields ranging from 49 to 77%. In addition, alpha-bromoketones and esters were found to undergo equally effective alpha-cyanation.