daidzein-7-ω-carboxyhexyl ether

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: daidzein-7-ω-carboxyhexyl ether
• 英文别名: hepzein；7-[3-(4-Hydroxy-phenyl)-4-oxo-4H-chromen-7-yloxy]-heptanoic acid；7-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyheptanoic acid
• 化学式: C₂₂H₂₂O₆
• 分子量: 382.413
• InChiKey: ZNEDSSZKKYIJTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对羟基苯乙酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 氢氧化钾 、 三氟化硼乙醚 作用下， 以 丙酮 为溶剂， 反应 100.5h， 生成 daidzein-7-ω-carboxyhexyl ether
  参考文献：
  名称：

  The Mitochondrial Monoamine Oxidase−Aldehyde Dehydrogenase Pathway:  A Potential Site of Action of Daidzin

  摘要：

  Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL, accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if any, antidipsotropic activity. These results, although inconclusive, are consistent with the hypothesis that daidzin may act via the mitochondrial MAO/ALDH pathway and that a biogenic aldehyde such as 5-HIAL may be important in mediating its antidipsotropic action.

  DOI：

  10.1021/jm990614i

文献信息

• Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism
  申请人：——

  公开号：US20030087814A1

  公开（公告）日：2003-05-08

  Compositions and methods for treating, preventing, or reducing alcoholism, in particular methods for increasing patient compliance with therapies that require the intake of an ALDH inhibitor comprising the step of administering a monoamine oxidase B inhibitor.

  治疗、预防或减少酗酒的组合物和方法，特别是提高患者对需要摄入 ALDH 抑制剂的疗法的依从性的方法，包括施用单胺氧化酶 B 抑制剂的步骤。
• METHOD FOR THE INHIBITION OF ALDH-I USEFUL IN THE TREATMENT OF ALCOHOL DEPENDENCE OR ALCOHOL ABUSE
  申请人：THE ENDOWMENT FOR RESEARCH IN HUMAN BIOLOGY, INC.

  公开号：EP0592583A1

  公开（公告）日：1994-04-20
• EP1441708A4
  申请人：——

  公开号：EP1441708A4

  公开（公告）日：2007-05-23
• COMPOSITIONS AND METHODS FOR INCREASING COMPLIANCE WITH THERAPIES USING ALDEHYDE DEHYDROGENASE INHIBITORS AND TREATING ALCOHOLISM
  申请人：Krele Pharmaceuticals LLC

  公开号：EP1441708A1

  公开（公告）日：2004-08-04
• TREATMENT FOR COCAINE ADDICTION
  申请人：Tonix Pharmaceuticals, Inc.

  公开号：EP2611440B1

  公开（公告）日：2017-02-01