(E)-3-(3,4-dimethoxyphenyl)-1-(3-pyridyl)prop-2-en-1-one | 53940-06-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3,4-dimethoxyphenyl)-1-(3-pyridyl)prop-2-en-1-one
• 英文别名: (E)-3-(3,4-dihydroxyphenyl)-1-(pyridin-3-yl)prop-2-en-1-one；DMU774；(E)-3-(3,4-dihydroxyphenyl)-1-pyridin-3-ylprop-2-en-1-one
• CAS: 53940-06-0
• 化学式: C₁₄H₁₁NO₃
• 分子量: 241.246
• InChiKey: FGVWMVPACIUGMM-HWKANZROSA-N

物化性质

• 沸点：
  476.5±45.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4-dimethoxyphenyl)-1-(3-pyridyl)prop-2-en-1-one 、 copper dichloride 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Hydroxy-substituted trans -cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (A beta), glycogen synthase kinase 3 beta (GSK-3 beta) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3 beta (IC50 = 24.36 +/- 0.01 mu M) and A beta(42) self-aggregation (IC50 = 9.0 +/- 1.4 mu M), to chelate copper (II) and to act as exceptionally strong radical scavenger (k(inh) = 6.8 +/- 0.5 . 10(5) M(-1)s(-1)) even in phosphate buffer at pH 7.4 (k(inh) = 3.2 +/- 0.5 . 10(5) M(-1)s(-1)). Importantly, compound 3 showed high predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 mu M and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.058
• 作为产物：
  描述：

  3,4-二(四氢吡喃-2-氧基)苯甲醛 在 对甲苯磺酸 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 生成 (E)-3-(3,4-dimethoxyphenyl)-1-(3-pyridyl)prop-2-en-1-one
  参考文献：
  名称：

  Hydroxy-substituted trans -cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (A beta), glycogen synthase kinase 3 beta (GSK-3 beta) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3 beta (IC50 = 24.36 +/- 0.01 mu M) and A beta(42) self-aggregation (IC50 = 9.0 +/- 1.4 mu M), to chelate copper (II) and to act as exceptionally strong radical scavenger (k(inh) = 6.8 +/- 0.5 . 10(5) M(-1)s(-1)) even in phosphate buffer at pH 7.4 (k(inh) = 3.2 +/- 0.5 . 10(5) M(-1)s(-1)). Importantly, compound 3 showed high predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 mu M and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.058

文献信息

• Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: Overcoming cisplatin resistance in CYP1B1-overexpressing lines
  作者：Neill J. Horley、Kenneth J.M. Beresford、Tarun Chawla、Glen J.P. McCann、Ketan C. Ruparelia、Linda Gatchie、Vinay R. Sonawane、Ibidapo S. Williams、Hoon L. Tan、Prashant Joshi、Sonali S. Bharate、Vikas Kumar、Sandip B. Bharate、Bhabatosh Chaudhuri

  DOI：10.1016/j.ejmech.2017.02.016

  日期：2017.3

  The structure of alpha-napthoflavone (ANF), a potent inhibitor of CYP1A1 and CYP1B1, mimics the structure of chalcones. Two potent CYP1B1 inhibitors 7k (DMU2105) and 6j (DMU2139) have been identified from two series of synthetic pyridylchalcones. They inhibit human CYP1B1 enzyme bound to yeast-derived microsomes (Sacchrosomes((TM))) with IC50 values of 10 and 9 nM, respectively, and show a very high level of selectivity towards CYP1B1 with respect to the IC50 values obtained with CYP1A1, CYP1A2, CYP3A4, CYP2D6, CYP2C9 and CYP2C19 Sacchrosomes((TM)). Both compounds also potently inhibit CYP1B1 expressed within 'live' recombinant yeast and human HEK293 kidney cells with IC50 values of 63, 65, and 4, 4 nM, respectively. Furthermore, the synthesized pyridylchalcones possess better solubility and lipophilicity values than ANF. Both compounds overcome cisplatine-resistance in HEK293 and A2780 cells which results from CYP1B1 overexpression. These potent cell-permeable and water-soluble CYP1B1 inhibitors are likely to have useful roles in the treatment of cancer, glaucoma, ischemia and obesity. (C) 2017 Elsevier Masson SAS. All rights reserved.
• 3,4-Dihydroxychalcones as potent 5-lipoxygenase and cyclooxygenase inhibitors
  作者：Satoshi Sogawa、Yasunori Nihro、Hiroki Ueda、Akihiro Izumi、Tokutaro Miki、Hitoshi Matsumoto、Toshio Satoh

  DOI：10.1021/jm00076a019

  日期：1993.11

  A novel series of 3,4-dihydroxychalcones was synthesized to evaluate their effects against 5-lipoxygenase and cyclooxygenase. Almost all compounds exhibited potent inhibitory effects on 5-lipoxygenase with antioxidative effects, and some also inhibited cyclooxygenase. The 2',5'-disubstituted 3,4-dihydroxychalcones with hydroxy or alkoxy groups exhibited optimal inhibition of cyclooxygenase. We found that 2',5'-dimethoxy-3,4-dihydroxychalcone (37; HX-0836) inhibited cyclooxygenase to the same degree as flufenamic acid and 6-lipoxygenase, more than quercetin. Finally, these active inhibitors of 5-lipoxygenase inhibited arachidonic acid-induced mouse ear edema more than phenidone.
• Hydroxy-substituted trans -cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease
  作者：Angela De Simone、Manuela Bartolini、Andrea Baschieri、Kim Y.P. Apperley、Huan Huan Chen、Melissa Guardigni、Serena Montanari、Tereza Kobrlova、Ondrej Soukup、Luca Valgimigli、Vincenza Andrisano、Jeffrey W. Keillor、Manuela Basso、Andrea Milelli

  DOI：10.1016/j.ejmech.2017.07.058

  日期：2017.10

  Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (A beta), glycogen synthase kinase 3 beta (GSK-3 beta) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3 beta (IC50 = 24.36 +/- 0.01 mu M) and A beta(42) self-aggregation (IC50 = 9.0 +/- 1.4 mu M), to chelate copper (II) and to act as exceptionally strong radical scavenger (k(inh) = 6.8 +/- 0.5 . 10(5) M(-1)s(-1)) even in phosphate buffer at pH 7.4 (k(inh) = 3.2 +/- 0.5 . 10(5) M(-1)s(-1)). Importantly, compound 3 showed high predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 mu M and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate. (C) 2017 Elsevier Masson SAS. All rights reserved.