3-amino-8-bromo-6-chloro-2-phenethylchromone | 1138464-61-5

• 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: 3-amino-8-bromo-6-chloro-2-phenethylchromone
• 英文别名: 3-Amino-8-bromo-6-chloro-2-(2-phenylethyl)chromen-4-one
• CAS: 1138464-61-5
• 化学式: C₁₇H₁₃BrClNO₂
• 分子量: 378.653
• InChiKey: DMYUPGSWWSDVGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-8-bromo-6-chloro-2-phenethylchromone 、 乙酸酐 在 吡啶 作用下， 以87%的产率得到N-(8-bromo-6-chloro-4-oxo-2-phenethyl-4H-chromen-3-yl)-acetamide
  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：

  8-Bromo-6-chloro-2-(2-phenylethyl)-2,3-dihydrochromen-4-one 在 sodium azide 、 copper(ll) bromide 作用下， 以 氯仿 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 3.17h， 生成 3-amino-8-bromo-6-chloro-2-phenethylchromone
  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

• Synthesis of 2-Alkyl-Substituted Chromone Derivatives Using Microwave Irradiation
  作者：Maria Fridén-Saxin、Nils Pemberton、Krystle da Silva Andersson、Christine Dyrager、Annika Friberg、Morten Grøtli、Kristina Luthman

  DOI：10.1021/jo802783z

  日期：2009.4.3

  A base-promoted condensation between 2-hydroxyacetophenones and aliphatic aldehydes has been studied. The reaction has been optimized to afford 2-alkyl-substituted 4-chromanones in an efficient manner using microwave heating. Performing the reaction using diisopropylamine in EtOH at 170 degrees C for 1 h gave moderate to high yields (43-88%). The 4-chromanones could be further converted into highly functionalized 2,3,6,8-tetrasubstituted chromones in which a 3-substituent (acetate, amine, or bromine) was introduced via straightforward chemical transformations.
• Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells
  作者：Tina Seifert、Marcus Malo、Tarja Kokkola、Karin Engen、Maria Fridén-Saxin、Erik A. A. Wallén、Maija Lahtela-Kakkonen、Elina M. Jarho、Kristina Luthman

  DOI：10.1021/jm500930h

  日期：2014.12.11

  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.