daidzein-7-ω-carboxydecyl 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-carboxydecyl ether
• 英文别名: 11-(3-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yloxy)undecanoic acid；11-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyundecanoic acid
• 化学式: C₂₆H₃₀O₆
• 分子量: 438.521
• InChiKey: QZLSDKZTRILVNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 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-carboxydecyl 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

• 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
• US5624910A
  申请人：——

  公开号：US5624910A

  公开（公告）日：1997-04-29
• US5886028A
  申请人：——

  公开号：US5886028A

  公开（公告）日：1999-03-23
• US6255497B1
  申请人：——

  公开号：US6255497B1

  公开（公告）日：2001-07-03
• [EN] 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：WO1993000896A1

  公开（公告）日：1993-01-21

  (EN) Method for inhibiting aldehyde dehydrogenase activity using daidzin and/or daidzin analog and/or daidzin or daidzin analog in combination with a factor or factors which increase the bioavailability of the daidzin or daidzin analog, as ALDH-I inhibitory compounds or compositions. Such inhibitory compounds or compositions are useful as pharmaceutical compositions in methods for the treatment of alcohol dependence (i.e., alcoholism) or alcohol abuse, for alcohol sensitization, for extinguishing an alcohol-drinking response, for suppressing an urge for alcohol, for inducing alcohol intolerance, for preventing alcoholism in an individual with or without a susceptibility or predisposition to alcoholism or alcohol abuse, and for limiting alcohol consumption in an individual whether or not genetically predisposed.(FR) Procédé servant à inhiber l'activité de déshydrogénase de l'aldéhyde au moyen de daidzine et/ou d'un analogue de daidzine et/ou de daidzine ou d'un analogue de daidzine combiné à un ou plusieurs facteurs augmentant la biodisponibilité de la daidzine ou de l'analogue de la daidzine, en tant que composés ou compositions inhibiteurs de l'ALDH-I. Ces composés ou compositions inhibiteurs sont efficaces en tant que compositions pharmaceutiques utilisées dans des procédés servant au traitement de la dépendance à l'alcool (c'est-à-dire, l'alcoolisme) ou l'abus d'alcool, à la sensibilisation à l'alcool, à la suppression de la réaction conduisant à la consommation d'alcool, à la suppression du besoin d'alcool, à la provocation de l'intolérance à l'alcool, à la prévention de l'alcoolisme chez un individu présentant ou non un terrain favorable ou une prédisposition à l'alcoolisme ou à l'abus d'alcool, ainsi qu'à la limitation de la consommation d'alcool chez un individu prédisposé génétiquement ou non.