7-chloro-2-(4-hydroxy-3-methoxyphenyl)-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: 7-chloro-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one
• 英文别名: 7-Chloro-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one；7-chloro-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
• 化学式: C₁₆H₁₁ClO₄
• 分子量: 302.714
• InChiKey: ZOAWIAVOXIKKMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,5-二羟基苯乙酮 在 双氧水 、 碘 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 7-chloro-2-(4-hydroxy-3-methoxyphenyl)-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

• 강심 활성을 갖는 크로메논 유도체 및 이를 포함하는 심부전의 예방 또는 치료용 약학 조성물
  申请人：The Industry & Academic Cooperation in Chungnam National University (IAC) 충남대학교산학협력단(220040084104) BRN ▼314-82-09264

  公开号：KR20170000426A

  公开（公告）日：2017-01-03

  본 발명의 신규 크로메논 유도체 및 이를 포함하는 심부전의 예방 또는 치료용 약학 조성물은, 심근 미오신 ATPase 활성화 효과 및 심실 근육수축을 증가시키는 효과가 우수하여, 심부전의 예방 또는 치료용 약물로 유용하게 사용될 수 있다.

  这篇文章描述了一种新型的克罗芒酮衍生物及其在预防或治疗心力衰竭中的药物配方。该药物具有优秀的心肌肌原ATP酶激活效应和增加心室肌肉收缩的效果，因此可用作预防或治疗心力衰竭的药物。
• 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.