6-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxy-4H-chromen-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 6-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxy-4H-chromen-4-one
• 英文别名: 6-Hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxychromen-4-one；6-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxychromen-4-one
• 化学式: C₁₇H₁₄O₆
• 分子量: 314.295
• InChiKey: YTTRSFJPGNVCTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,5-二羟基苯乙酮 在 双氧水 、 sodium hydride 、 potassium hydroxide 、 sodium hydroxide 、 碘甲烷 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 6-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  Exploration of Pharmacophore in Chrysosplenol C as Activator in Ventricular Myocyte Contraction

  摘要：

  Chrysosplenol C (4',5,6-trihydroxy-3,3',7-tri-methoxyflavone) isolated from Miliusa balansae has unique structural features as a reversible inotropic agent independent of beta-adrenergic signaling and with selective activation of cardiac myosin ATPase. Hence, a series of chrysosplenol analogues were synthesized and explored for identification of pharmacophore that is essential for the increasing contractility in rat ventricular myocytes. Analogue 7-chloro-2-(3-hydroxypheny1)-3-methoxy-4H-chromen-4-one showed highly potent contractility (54.8% at 10 mu M) through activating cardiac myosin ATPase (38.7% at 10 mu M). Our systematic structure activity relationship study revealed that flavonoid nucleus of chrososplenol C appears to be an essential basic skeleton and hydrophobic substituent at position 7 of chromenone such as methoxy or chloro enhances the activity. Additionally, our ATPase study suggested that these chrysosplenol analogues have selectivity toward cardiac myosin activation. Thus, the novel flavonone with 3-/7-hydrophobic substituent and 3'-hydrogen bonding donor function is a novel scaffold for discovery of a new positive inotropic agent.

  DOI：

  10.1021/acsmedchemlett.5b00043

文献信息

• Exploration of Pharmacophore in Chrysosplenol C as Activator in Ventricular Myocyte Contraction
  作者：Eeda Venkateswararao、Min-Jeong Son、Niti Sharma、Manoj Manickam、PullaReddy Boggu、Young Ho Kim、Sun-Hee Woo、Sang-Hun Jung

  DOI：10.1021/acsmedchemlett.5b00043

  日期：2015.7.9

  Chrysosplenol C (4',5,6-trihydroxy-3,3',7-tri-methoxyflavone) isolated from Miliusa balansae has unique structural features as a reversible inotropic agent independent of beta-adrenergic signaling and with selective activation of cardiac myosin ATPase. Hence, a series of chrysosplenol analogues were synthesized and explored for identification of pharmacophore that is essential for the increasing contractility in rat ventricular myocytes. Analogue 7-chloro-2-(3-hydroxypheny1)-3-methoxy-4H-chromen-4-one showed highly potent contractility (54.8% at 10 mu M) through activating cardiac myosin ATPase (38.7% at 10 mu M). Our systematic structure activity relationship study revealed that flavonoid nucleus of chrososplenol C appears to be an essential basic skeleton and hydrophobic substituent at position 7 of chromenone such as methoxy or chloro enhances the activity. Additionally, our ATPase study suggested that these chrysosplenol analogues have selectivity toward cardiac myosin activation. Thus, the novel flavonone with 3-/7-hydrophobic substituent and 3'-hydrogen bonding donor function is a novel scaffold for discovery of a new positive inotropic agent.